Tribute

Sumner Yaffe, M.D. May 9, 1923 - August 10, 2011

Sumner Yaffe

Sumner Yaffe M.D. was widely regarded as the father of pediatric clinical pharmacology.

It was through his tireless efforts and unwavering commitment to pediatric pharmacology, his research creativity, his exemplary leadership and his warm and gentle humanity, that Sumner Yaffe has changed the face of therapeutics in infants and children.

He began his studies at Harvard College — interrupted by a wartime service in the Office of Strategic Service — where he earned an AB in chemistry. He then earned his M.A. in Pharmacology at Harvard University, became a physician after studying at the University of Vermont, and completed an internship and residency Boston Children’s Hospital. After a Fullbright scholarship study at Saint Mary’s Hospital in London, he completed a fellowship under Robert Schwartz at Harvard.

Dr. Yaffe continued his career in faculty positions at Stanford University, Buffalo Children’s Hospital, the Karolinska Institute, and the Children’s Hospital of Philadelphia.

During his distinguished academic career, he published upwards of 300 scientific articles and books dealing with a wide range of developmental science: Drugs in Lactation (with Gerald G. Briggs and Roger K. Freeman) and Pediatric Pharmacology (with Jacob V. Aranda).

In 1980, Dr. Yaffe became director of the Center for Research for Mothers and Children at the NICHD, influencing and molding research policies for 20 years. He created the neonatal and the fetal maternal medicine networks and continued the fight for the study of drugs in children.

It was the result of a recommendation from the Forum on Drug Development of the Institute of Medicine workshop that led to his crowning achievement: the creation of the pediatric pharmacology research units (PPRUs) network.

Dr. Yaffe devoted time and energy to many scientific advisory committees and innumerable academic and professional associations, but above all, he was a doting and loving father. He is survived by his beloved wife Sussane, five sons, one daughter and five grandchildren.

Remembrances of Dr. Sumner Yaffe from friends and colleagues:

Sumner and Christine Yaffe

Yaffe with his daughter, Christine Yaffe, M.D.,
a CNS pharmacologist. Note the bow tie —
he was a snappy dresser!

I first met Sumner Yaffe in the 1970s, shortly after I had moved to Penn State Hershey (now Penn State Children's Hospital). We shared an interest in pediatric pharmacology as well as having both been trained at the Boston Children's Hospital. I was recruited to Penn State by the original Chair of Pediatrics, Dr. Nicholas Nelson. Sumner was the first person Nick met when NIck arrived at Boston Children's as an intern. I was fortunate to be able to take a sabbatical with Sumner at the Children's Hospital of Philadelphia from 1979 to 1980. We discussed many issues in pediatric therapeutics, and I was able to do laboratory work in the area of drug excretion into breast milk. Over the years we have collaborated in many projects, my favorite being the 4 editions of his and Jack Aranda's text on Neonatal and Pediatric Pharmacology.

His contributions to the field of pediatrics are both many and diverse. His original interest was in renal disease and for several years ran a renal clinic at Stanford. He became interested in fetal neonatal pharmacology, and one of his most important contributions in this field was the demonstration that phenobarbital influenced the conjugation of bilirubin in newborn infants. He was one of the first persons to be interested in the issue of compliance in children taking medications. The spectrum of his activity is illustrated by his publishing papers and books over 6 decades with nearly 300 publications. Drugs in Pregnancy and Lactation, written with Gerald Briggs and Roger Freeman is a classic. He was a constant innovator and a font of ideas which he was very willing to share with young investigators. He loved to challenge us with what initially appeared to be far out ideas, only for us to learn that he was ahead of us.

His constant championship of the child culminated in the creation of the PPRU sponsored by the National Institute of Child and Human Development (NICHD) of the National Institutes of Health (NIH). This Network, initially developed to extended the drug labeling of compounds to the pediatric population, expanded to include translational research for both new compounds and new uses of old drugs. The network was extremely influential in increasing the awareness of the importance of drug therapy to many groups including regulatory and legislative bodies.

His legacy to us is to improve therapy for children, the critical importance of collaboration, and the emphasis on education of further generations. We celebrate his legacy, his friendships, and his enthusiasm and devotion for the care of children. Truly, he is the father of pediatric pharmacology. — Cheston M. Berlin, Jr., M.D.

Yaffe speaks

It is straightforward to state that Sumner J. Yaffe was a giant figure as a founder of the discipline of pediatric and developmental pharmacology. In this sense, he was a visionary figure. However, he knew almost better than anyone in the field how to influence policy at the level of the Federal government, within the organizations of pediatrics and pharmacy, at the interface of pharmaceutical companies and medical groups, and in terms of the training of future pharmacologists. He was especially savvy about the political process required to assure safer and more appropriate medications for children of all ages. In his most recent textbook, Neonatal and Pediatric Pharmacology, which he edited with Jack Aranda, the subtitle is Therapeutic Principles in Practice. This latter phase sums up a typical Sumner J. Yaffe approach. I urge you to read his chapter on the historical perspective to gain even greater insight into the man. — Russell Chesney, M.D.

Yaffe on ship

I first came to recognize the expertise and leadership of Dr. Yaffe during his years at Buffalo through his publications and presentations at national meetings.  Later, I had the privilege of working with Sumner when he chaired the American Academy of Pediatrics (AAP) Committee on Drugs and as one of the original investigators in the PPRU.  He was a tireless and disciplined leader who brought great passion for improving drug therapy in children through rigorous science.  Through his leadership, the Committee on Drugs became the leading advocate within and without the AAP for improved pediatric therapeutics.  He subsequently carried this passion to his research, teaching, and publishing while at The Children's Hospital of Philadelphia (CHOP).  Dr. Yaffe's lifelong dedication to pediatric therapeutics culminated during his tenure at NICHD where his vision and leadership lead to successful implementation of a network of pediatric pharmacology units funded by NICHD.  The successor programs at NICHD that are carrying forward the commitment to research in pediatric therapeutics are a fitting recognition of the legacy Dr. Yaffe left us.  He will be missed, but leaves us with a broad and deep legacy to build on.
— Ralph E. Kauffman, M.D.

“Dr. Yaffe's vision of improved therapy for sick children is becoming a reality. He has inspired an entire generation of pediatric clinical pharmacologists to grow the field into a mature and evolving scientific discipline.” — Stephen P. Spielberg, M.D., Ph.D.

Yaffe and friends

Yaffe, Caritis and Aranda at the European Society of Developmental
Pharmacology meeting in Chamonix, France, June 2009

Without having had the pleasure of ever receiving a grade from Dr. Yaffe (to my knowledge, at least), he unwittingly became one of my first instructors in this field. As an undergraduate student at the St. Louis College of Pharmacy in 1976, I had the good fortune to be selected by one of my professors to be one of 10 students who would be “permitted” to participate in a newly designed, eight-week clinical rotation. In this evolution, pharmacy students were to be inserted into a medical practice setting for the purpose of observing the decision-making process as it related to the selection and prescription of drugs. Consequent to a genuine twist of fate, I was instructed to report to the Pediatric Allergy Clinic located in the St. Louis Children's Hospital. Knowing really nothing of either pediatric allergy or pediatric therapeutics, I was convinced that some time in the library was in order. A cursory review of the contemporary literature revealed an article co-authored by Dr. Yaffe which was entitled “Inadequacies in the Pharmacologic Management of Ambulatory Children,” a paper that was quite critical of dispensing errors (e.g., incorrect volume of liquid antibiotics, incorrect labeling) and also indicated complete compliance with antibiotic treatment for otitis media occurring only 7.3% of the time. In considering this information, two revelations became immediately apparent to me: 1) children were different, and 2) professional intervention by a pharmacist might just make the difference between effective and failed therapy. Having successfully completed this “experimental” rotation, I had the good fortune in my 5th year of pharmacy school to arrange an elective clinical research experience in the labor and delivery unit at Barnes Hospital. A significant portion of this experience was focused on collecting information on the effects of anesthetic and analgesic drugs administered in the immediate peripartum period, and thereby provided me with a first taste of clinical investigation. In asking for relevant background reading, I remember being given a review article authored by Dr. Yaffe entitled “Drugs and Pregnancy.” By this time, I was totally convinced that pediatric pharmacology was a most noble and necessary pursuit. For this early directional influence and the knowledge gained from Dr. Yaffe's exemplary works and faithful example, I will remain eternally grateful. — Gregory L. Kearns, Pharm.D., Ph.D.

Dr. Sumner J. Yaffe

I met Sumner first in March 1983 at the first American Society Clinical Pharmacology Therapeutics (ASCPT) I participated in San Diego. During 1978-82, when I had made my career decision toward pediatric pharmacology, I read everything he had written as the founder of our discipline. Meeting him was for me, I guess, what goes through the minds of fans of a rock star. The difference was that the typical rock star spends a second with the fan; whereas Sumner gave me right away the feeling he was rejoicing the addition of a young pediatrician to the discipline. During the poster session of the meeting, he invited me to submit our paper to Pediatric Pharmacology, the journal he had just started. It is difficult to describe how happy I was. The subsequent years have proven that this welcome was real and tangible, with his support and advice in every step of my career, in thick and thin.

He visited us in Toronto several times and his warmth, friendliness and amazing knowledge and experience were critical to our development. Sumner's ability to convince the NIH to establish the PPRU system has revolutionized our discipline and is now being studied and repeated in other parts of the world.

Sumner's charisma, passion, and warmth will be with me forever. — Gideon Koren M.D., FRCPC, FACMT

Yaffe and his children

I first met Sumner many years ago as a co-reviewer for an NIH project and long before our center joined the PPRU. He was among the first and strongest supporters of the therapeutic orphan concept and had a very positive effect on my career of pursuing clinical pharmacologic studies of antimicrobials in infants and young children.
— George H. McCracken, Jr., M.D.

Yaffe speaks

Sumner arrived to Stockholm and Karolinska Institutet in 1969 to spend a sabbatical at our department of clinical pharmacology by invitation from my former chief and predecessor, professor Folke Sjöqvist. Sumner was the one that introduced me into the exciting and intellectual world of developmental pharmacology. He did it with great enthusiasm and in a way that captured me for life in this research area, albeit I later acquired some other main interests as well.

He had a capacity to bridge the gap between basic and clinical sciences. One example was our early biochemical studies of the development of the monooxygenase system in the human fetus. Absence or severe malfunction of this system may not be compatible with continued normal life or physiology. Sumner had numerous examples of this from his experience in pediatric medicine and pharmacology and he used his excellent pedagogic talents to describe the relation between metabolism and health and disease in children.

Sumner was very much liked by the staff at our department, not the least because everyone was impressed by his benchwork achievements (which included even dishwashing!).

I remember nostalgically the nice social relations and many occasions when Kristina and I met him and his nice family.

We have kept close contact with Sumner ever since at many meetings in various places of the world. It was a great pleasure to have him as guest at the second Swedish European Society for Developmental Perinatal & Pediatric Pharmacology (ESDPPP) Congress, which took place in Stockholm in 2006.

Sumner has played a key role for the development of pediatric drug therapy. He has also catalyzed the communication of knowledge to the medical community, the society, and regulatory bodies about the urgent need of documented drugs for children of various ages. His efforts paved the way for today's regulations of development of drugs for children, not only in the United States, but also in the European Union.

We keep Sumner in grateful memory. — Anders Rane, M.D. Ph.D.

Yaffe and his son

Yaffe and his youngest son Zachary in Gruyere
Switzerland, June 2009

I had the great fortune to meet Dr. Sumner Yaffe during my training time in Buffalo, New York. He offered me the opportunity to work in his lab on a project related to developmental aspects of acetaminophen metabolism. I met with him regularly at our weekly research meetings to review data. This was about 1974. He once told me about his vision to develop a pediatric pharmacology center and a network of investigators. I watched him move from Buffalo to Philadelphia and then to NICHD where he managed to pull off this idea and develop the NICHD PPRU Network. That was pretty amazing to witness the events unfold over time. That taught me a life lesson on vision and persistence.

I also had the opportunity to participate in his dream as a member of the PPRU, watch the transition of labeling of medications to children, and watch studies develop that would have never happened prior to this landmark change in direction.

While I often thought of Sumner as the first “political pharmacologist” in my lighter moments, his contributions to the development of pediatric clinical pharmacology will forever be remembered. He was a major stimulus to my career and to many of my colleagues.

Sumner, I am sure you are in a better place and you are already making contacts to improve our care of sick children.— Stanley J. Szefler, M.D.

Yaffe

Remembering Sumner: my teacher, mentor, boss, and friend:

I first met Sumner in Baltimore Airport for an interview when I was applying for a fellowship in his pediatric clinical pharmacology program at the State University of New York at Buffalo (SUNY). Sumner had a busy schedule and the airport was the most expedient meeting place. Since we did not know each other, Sumner suggested exchanging photographs so we could recognize each other. He was very warm and easy to talk to. We were able to communicate in half sentences as we knew what the other was going to say. This ability of exchanging thoughts without words persisted until his death 40 years later.

I first learned about Sumner when I read a review article he wrote in the Annals of Internal Medicine on pediatric pharmacology with emphasis on the lack of knowledge in the use of drugs in newborns. At the time I was a fellow in neonatology and his article motivated me to pursue that line of research. Because Sumner had the only program that emphasized neonatal pharmacology, I moved to Buffalo. At that time there was great interaction between Sumner’s program and the department of biopharmaceutics at SUNY where Gerhard Levy and Milo Gibaldi developed the fundamental principles of pharmacokinetics. I remember the lively scientific discussions and marveled at Sumner’s insights and depth of knowledge. He had a great sense of humor and was very gregarious.

We shared time outside of the office. He would never wear an overcoat in the dreadful winters in Buffalo provided that he had gloves. I remember playing croquet in his house and ping-pong with his daughter Christine.

After I completed the fellowship, I became Director of Neonatology at the Buffalo Children’s Hospital and continued to collaborate with Sumner in developmental pharmacology studies. For a brief period, he became Chair of Pediatrics and thus my boss. He was always supportive of the initiatives that I undertook.

In 1975, Sumner moved to Philadelphia as Director of Clinical Pharmacology at CHOP. We remained in contact and wrote articles together.

After he became the Director of the Center for Mothers and Children, he asked me to apply to become the Project Officer of the newly created Pediatric Clinical Pharmacology Network. This was a very exciting period as we worked together to develop a strategy for the study off-patent drugs. In 1997, the FDA developed a proposal known as the Pediatric Rule of 1998 requiring companies to study drugs for labeling in pediatrics — this final rule eventually became the Pediatric Research Equity Act (PREA) — and asked for NIH input. The FDA original version did not include the study of drugs in newborns, so Sumner and I wrote the NIH response detailing the rationale for including newborns.

Without a doubt the most treasured memory was a day in August 1997 when I received a call from the White House inviting Sumner, Gilman Grave, Duane Alexander, and me to attend a ceremony in which President Clinton announced an executive order to implement the FDA Pediatric rule. I will never forget his reaction of disbelief and happiness. At long last his dream of so many years was finally realized!

Although I am extremely saddened by his death, I find comfort in the fact that I was able to talk to him a few days before his death and thank him for all he did for me. — George P. Giacoia M.D.

Yaffe and his colleagues

Dr. Catz, Dr. Delivoria, Dr. Aranda, and Dr. Yaffe

Sumner Yaffe was my mentor, a colleague, and a dear friend. As a resident I started to work in his laboratory at Stanford University and became very interested in Pediatric Pharmacology. This is not surprising as his enthusiasm and dedication to increase knowledge for the improvement of child care was contagious. When he moved to the State University of New York at Buffalo, he invited me to join the Pediatric Department. At the time he moved to Philadelphia, I joined the NICHD, which he joined later. Our collaboration continued, and I am surprised when I start to count that we worked together for more than 50 years (a whole life!!), attending meetings, planning diverse research activities, publishing, and on and on…

Sumner's enthusiasm and interest in expanding knowledge continued throughout his life. Our yearly participation at the Aspen Conference resulted in an invitation to stay at his home where in the evening, while listening to classical music with a glass of red wine in hand, we discussed some of the day's happenings prior to dinner.

Sumner is an unforgettable friend. — Charlotte Catz, M.D.

Yaffe at a party

Sumner was an all-time mentor to many people and to me, way before he came to Philadelphia in 1975.  When he arrived, I was so impressed with his kind personality, his wonderful smile, his ability to make anyone to fill comfortable with him, and his beautiful ideas in the field of neonatal pharmacology.

Going to his office at CHOP, away from my physiology laboratory, was a big treat from a hard load of work and research problems to resolve. Sumner would listen quietly and then give me some simple solutions that I often would say, “How come I did not think of that?”

Frequently he would come to my Research Neonatal Laboratory to discuss new projects that he thought about, and he would introduce me to his fellows and visiting professors. That was a fun time in the late 1970s, meeting with him, Paul Vert, and George Lambert amongst instruments and benches, arguing and discussing experimental data.  These are days that I remember with nostalgia because, then research was a spontaneous discussion of new ideas with limited paperwork and administrative restrictions.

For the entire time that Sumner and I were at the same work place, we also became good friends for a life time.

From his NIH major post he continued to guide me, counseling me and consoling me on grants and grant applications. He always had good words for me. He gave me the great honor to assist in the birth of his last child, Zachary, whom I took care of in my nurseries. What a wonderful father he was for this little premature baby. When he asked me how the baby was, I had only one answer that made him so happy, “Sumner, Zachary is a very cute baby, who looks like you, and we love him.” Sumner was very grateful for the care I gave Zachary in my old preemie nursery at Hospital of the University of Pennsylvania (HUP).

We spoke throughout the years, often enough to follow not only Zachary as he grew to become now a young man, but also of many other things.

In his old age, Sumner remained as young in his heart and mind as when I had first met him.  He will live in my heart and memory forever as I respected and loved him.

— Maria Delivoria-Papadopoulos, M.D.