David A. Karnofsky's Early Contributions to Cancer Research Helped Establish Oncology as a Medical Discipline 


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Dave was a fountain of ideas, stimulating all those around him to new and better research while constantly helping them with wise counsel to be critical of their own results.

—Joseph H. Burchenal, MD

For nearly 30 years, from the time he was a young resident at the Collis P. Huntington Memorial Hospital for Cancer Research of Harvard University, until his death from lung cancer on August 31, 1969, David A. Karnofsky, MD, dedicated himself to the pursuit of scientific excellence and the investigation of more effective therapies for cancer.

Dr. Karnofsky’s early research discoveries at Memorial Hospital–Sloan-Kettering Institute (now Memorial Sloan-Kettering Cancer Center) in New York led to the development of numerous chemotherapeutics, including the first oral alkylating agent triethylenemelamine, the glutamine antagonists azaserine (NSC 742) and 6-diazo-5-oxo-L-norleucine (DON), and two breakthrough agents widely used today in the treatment of childhood leukemias, daunorubicin and asparaginase (Elspar). In fact, his early clinical trials of asparaginase on 400 cancer patients proved so effective, especially in the treatment of acute lymphoblastic leukemia (ALL), it has been in common use in pediatric ALL for over 30 years.

Disciplined Approach to Oncology

Dr. Karnofsky’s meticulous attention to the clinical evaluation of drugs, which brought hard-data reliant objectivity and discipline to cancer research, is one reason he is credited with helping establish the field of oncology as a specific medical discipline. His creation in 1949 of the Karnofsky Performance Scale (along with another early pioneer of cancer chemotherapeutics, Joseph H. Burchenal, MD) is another. 

“The relevant matter in examining any form of treatment is not the reputation of its proponent, the persuasiveness of his theory, the eminence of its lay supporters, the testimony of patients, or the existence of public controversy, but simply … does the treatment work?” said Dr. Karnofsky in 1959.

“Dr. Karnofsky brought a very disciplined approach to the field of oncology,” said Michael Link, MD, Immediate Past President of ASCO and the Lydia J. Lee Professor of Pediatrics at Stanford University School of Medicine. “The Karnofsky Performance Scale not only provided physicians with the first tool to evaluate a patient’s clinical status, it also enabled them to objectively quantify the effectiveness of treatment and establish whether a drug was beneficial or not. That is the sort of real-science approach we want in the development of anticancer agents, and Dr. Karnofsky was the driving force behind that approach.”

Modern Age of Chemotherapy

In 1942, Dr. Karnofsky began studying the biological activities of mustard gas, a chemical warfare agent, at the Mount Desert Island Biological Laboratory in Maine. He continued that research after joining the Army Chemical Warfare Service, then a branch of the U.S. Army. It was while in the Army that Dr. Karnofsky became interested in the antineoplastic activity of nitrogen mustard (mechlorethamine [Mustargen]), which had been found to be effective, albeit briefly, against lymphoma.

His commanding officer at the time was C.P. Rhodes, MD, on leave as Medical Director of the Memorial Hospital for Cancer. At the end of World War II, in 1945, Dr. Karnofsky joined Dr. Rhodes at Memorial Hospital and, with Dr. Burchenal, launched the first organized clinical chemotherapy program in the country, and continued studies of nitrogen mustard and other antitumor cancer drugs.

“It was these experiences, many of us believe, that initiated the modern era of cancer chemotherapy,” said Irwin H. Krakoff, MD, in his remarks at the 24th Annual David A. Karnofsky Memorial Lecture, which were later published in the Journal of Clinical Oncology.1

In addition to being a researcher, clinician, and teacher, designing a course in chemotherapeutics for medical students, Dr. Karnofsky also traveled the world giving lectures on cancer research and was the recipient of numerous awards, including the Shabanu Medal for Cancer Research from the Empress Farah of Iran in 1968.2

Honoring the Early Cancer Pioneers

After Dr. Karnofsky’s death, a group of his friends donated money to ASCO to fund a yearly lecture at ASCO’s Annual Meeting, and in 1970, ASCO launched a permanent memorial to honor Dr. Karnofsky’s body of work with the David A. Karnofsky Memorial Award and Lecture. The Award, which is presented at ASCO’s Annual Meeting, recognizes oncologists who have made outstanding contributions in the areas of cancer research, diagnosis, and/or treatment and is the Society’s highest scientific honor.

The first Award recipient was Sir Alexander Haddow, FRS, whose lecture, “Thoughts on Chemical Therapy,” addressed his concern that scientists would never be able to develop drugs that can discriminate cancer cells from normal cells, making it impossible, he thought, to develop targeted therapies to kill malignant cells. The 2012 recipient of the Karnofsky Award is Kanti R. Rai, MD, the creator of the Rai clinical staging system for chronic lymphocytic leukemia.

“The list of recipients of the David A. Karnofsky Memorial Award reads like a Who’s Who in oncology,” said Dr. Link. “It is important to acknowledge our forbearers. Sometimes we forget the important work done by our earlier cancer pioneers and take for granted their struggles and the progress that has been made. So much of the early studies in chemotherapy were done in childhood cancers. If we hadn’t had the kind of successes we’ve had in treating pediatric cancers, I’m not sure there would be the kind of interest we see in the field of oncology and in chemotherapy, because it is success that encourages more scientific work and optimism,” said Dr. Link.

‘A Great and Dedicated Physician’

At the time of his death, Dr. Karnofsky was Chief of the Medical Oncology Service and Head of the Division of Chemotherapy Research at the Sloan-Kettering Institute for Cancer Research, Professor of Medicine at Cornell University Medical Center, and a physician at The New York Hospital.

Dr. Karnofsky’s contributions as a scientist, physician, and teacher in the fledgling field of oncology were summed up in an obituary written by Dr. Burchenal, Dr. Karnofsky’s friend and colleague at the Sloan-Kettering Institute. “Dave was a fountain of ideas, stimulating all those around him to new and better research while constantly helping them with wise counsel to be critical of their own results.… We at Memorial have been immensely fortunate to have had more than 2 decades of association with him as a friend, a distinguished and truly creative scientist, a careful and exact clinical investigator, a wise counselor, and, most important of all, a great and dedicated physician,” wrote Dr. Burchenal.2

The 2013 Karnofsky lecture will be presented on June 1 at the ASCO Annual Meeting. ■

References

1. Krakoff IH: The 24th annual David A. Karnofsky memorial lecture. Progress and prospects in cancer treatment: The Karnofsky legacy. J Clin Oncol 12:432-438, 1994.

2. Burchenal JH: Obituary: David A. Karnofsky. Cancer Res 30:549-550, 1970.



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