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


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David A. Karnofsky, MD

David A. Karnofsky, 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. In fact, his early clinical trials of asparaginase in 400 patients with cancer proved so effective, especially in the treatment of acute lymphoblastic leukemia (ALL), it has been in common use in pediatric ALL for more than 30 years.

Disciplined Approach to Oncology

Dr. Karnofsky’s meticulous attention to the clinical evaluation of drugs, which brought reliant hard-data objectivity and discipline to cancer research, is one reason he is credited with helping to 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.

Modern Age of Chemotherapy

In 1942, Dr. Karnofsky began studying the biologic 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. While in the Army, Dr. Karnofsky became interested in the antineoplastic activity of nitrogen mustard (mechlorethamine), which had been found to be effective, albeit briefly, against lymphoma.

Celebrating 10 Years of The ASCO Post: A Retrospective

The ASCO Post launched 10 years ago at the 2010 ASCO Annual Meeting. In the coming months, we’ll be publishing a retrospective series of article selections, looking back at some of the highlights published over the past decade. This article, “David A. Karnofsky’s Early Contributions to Cancer Research Helped Establish Oncology as a Medical Discipline,” was originally published in The ASCO Post on February 15, 2013.

We would love to hear what The ASCO Post means to you and how we may continue to serve the needs and interests of our readers. Contact editor@ASCOPost.com. 

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, continuing studies of nitrogen mustard and other anticancer drugs.

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.

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. 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 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 list of recipients of the David A. Karnofsky Memorial Award reads like a Who’s Who in oncology,” said Michael Link, MD, Immediate Past President of ASCO and the Lydia J. Lee Professor of Pediatrics at Stanford University School of Medicine. “It is important to acknowledge our forebearers. 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 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.

MORE INFORMATION

The 2020 recipient of the Karnofsky Memorial Award and Lecture was George Demetri, MD, FASCO. Dr. Demetri is Professor of Medicine and Co-Director of the Ludwig Center at Harvard Medical School. He was recognized for pioneering the development of targeted kinase inhibitors (including imatinib, sunitinib, and regorafenib) for gastrointestinal stromal tumors and for his role in the development of several other therapies for sarcomas.

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: “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.”1 

REFERENCE

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


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