I am deeply saddened to have to let you know of the passing of our longtime colleague, mentor and friend, Thomas A. Waldmann, M.D., Chief Emeritus of the Lymphoid Malignancies Branch and NIH Distinguished Investigator.
The words that have been most frequently used in the early tributes to Tom are “giant,” “legend” and “pioneer.” Tom was an immunologist extraordinaire whose more than 60-year scientific odyssey at the National Cancer Institute resulted in numerous high-impact discoveries that have advanced the fields of organ transplantation, autoimmune disease and cancer. He was a leader in the study of cytokines and their receptors and of monoclonal antibodies, now a dominant form of cancer immunotherapy.
Tom received his M.D. from Harvard Medical School in 1955 and joined NCI in 1956 after finishing his residency at Massachusetts General Hospital. At NCI, he started his research by studying how the body metabolizes proteins, including immunoglobulins, in the blood. By 1959, he had become a senior investigator, and his research had expanded to include work with patients with primary immunodeficiency diseases and disorders of lymphatic channels. Tom became chief of the Lymphoid Malignancies Branch in 1971.
Tom’s pivotal studies revolutionized our understanding of the roles played by the interleukin-2 (IL-2) receptor and interleukin-15 (IL-15) receptor cytokine systems in the life and death of T lymphocytes. In characterizing the first cytokine receptor, IL-2, his team set the stage for understanding the biology and biochemistry of this family of molecules and then demonstrated that antibodies specific for the IL-2 receptor were useful in treating adult T-cell leukemia, prolonging survival of transplant recipients, and treating multiple sclerosis.
In 1994, Tom and his team co-discovered the cytokine IL-15. Like IL-2, IL-15 triggers the production of immune cells that attack and kill cancer cells. Tom’s group initiated the first-in-human IL-15 clinical trial in 2011, which showed IL-15 dramatically increased growth and activity of T and Natural Killer cells. Furthermore, Tom initiated clinical trials to evaluate IL-15’s capacity to augment antibody-dependent cellular cytotoxicity when administered with tumor directed monoclonal antibodies. He demonstrated complete responses in select patients with human T-cell leukemia virus (HTLV)-associated adult T-cell leukemia/lymphoma using this approach. This work exemplifies his passionate pursuit for developing therapeutics for cancer and AIDS.
Tom should also be remembered for his other accomplishments. Prior to 1980, he studied the metabolism of serum proteins, which led him to identify a rare disorder of the gastrointestinal tract now known as Waldmann’s disease. He devised a novel form of molecular genetic analysis to improve diagnosis and treatment of leukemia. In 1981, he helped treat the first patient with AIDS at NIH. And in 2016, the Food and Drug Administration approved daclizumab, the antibody he discovered, for use in the therapy of relapsing multiple sclerosis.
He was also an outstanding mentor. Many former fellows in the Lymphoid Malignancies Branch became branch chiefs within the NIH or took important positions outside of the NIH. Twenty-five postdoctoral fellows were elected to the American Society for Clinical Investigation, 20 were elected to the Association of American Physicians, seven were elected to the National Academy of Sciences USA and one received the Nobel Prize.
Collectively, Tom’s career was full of tremendous originality and scientific novelty. He has contributed to research accelerating progress in cancer that has major implications for future discoveries. His over 880 publications and over 100 named honorary lectures or keynote addresses have had an enduring impact on the work of others and has led to his receipt of countless honors, including but not limited to the Health and Human Services Career Achievement Award, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the Paul Ehrlich Medal, the Abbott Laboratory Prize in Clinical Diagnostic Immunology, the AAI-Ralph Steinman Award for Human Immunology Research, and the Service to America Career Achievement Award. Tom was also a member of several societies, including the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and he was an Honorary Fellow of the Royal Society of the Medical Sciences (UK).
I’d like to leave you with a quote of Tom’s from the Washington Post that represents his attitude toward science and mentorship. “Science is a river,” he said. “You’re always building on the past. You might be able to turn over a rock and find something exciting; you don’t want to give up and say, ‘This is all there is.’ . . . It’s like planting a fruit tree that has a long duration, and when it comes time to harvest the oranges or whatever, you don’t want to leave.”
Many will stand on the shoulders of this giant and will continue to turn over the rocks to make new discoveries inspired by Tom’s lasting legacy.
Tom Misteli, Ph.D.
P.S. Tom Waldmann’s service over the years to NIH has been extraordinary. For many years he chaired the Subcommittee of the Central Tenure Committee on Clinical Investigators, and was a powerful voice supporting clinical and translational researchers at the NIH. I am personally grateful for his wise counsel and detailed analysis of many issues related to clinical research at the NIH. The NIH Catalyst featured him in an historic perspective in the Sept–Oct 2018 issue of The NIH Catalyst, at https://irp.nih.gov/catalyst/v26i5/thomas-a-waldmann-md
Michael Gottesman, M.D.
Deputy Director for Intramural Research, NIH