Kendall A. Smith

Kendall A. Smith, M.D.

After graduating summa cum laude from the Ohio State University College of Medicine, Dr. Smith trained in Medicine at Yale-New Haven Hospital, and in Hematology/Oncology at the National Cancer Institute. Subsequently, while a postdoctoral fellow at Dartmouth Medical School and L’Institut de Cancerologie et d’Immunogenetique in Villejuif France, Dr. Smith embarked an investigative career that focused on fundamental studies of cell proliferation.

On the faculty at Dartmouth Medical School for 20 years, Smith focused on basic research into how the immune system operates and made several fundamental discoveries that transformed our understanding of immunity. Dr. Smith’s research team created the first antigen-specific monoclonal cytolytic T lymphocytes (T cells), which revolutionized the study of T cells. This advance allowed Smith and his team to discover, characterize, and purify interleukin 2 (IL2) molecules to homogeneity, the first interleukin activity to be defined at the molecular level. This advance allowed them to demonstrate that IL1 and IL2 are distinct cytokines, thereby providing the scientific rationale for the interleukin nomenclature. There are now 43 interleukin molecules known. Using purified radiolabeled IL2, they then went on to discover and characterize the IL2 receptor, which was the first cytokine receptor to be described.

Further research at Weill Cornell University in New York City revealed that the cell determines to divide by counting the number of receptor “hits” delivered by IL2 and has led Dr. Smith to propose that this mechanism is responsible for exquisite normal cell growth control. Moreover, there are negative feedback loops in place that regulate the immune response via control over the expression of IL2 and other cytokines. This insight has led Smith to propose a new theory to explain how the immune system operates, “The Quantal Theory of Immunity”, published in 2010.

Appreciation of the quantal molecular mechanisms responsible for the regulation of the immune response has resulted in the understanding of the mutational pathogenesis of leukemias and most other cancers, severe autoimmune disorders, and primary immunodeficiencies. In addition, these molecular advances have led to the use of new combination immunosuppressive therapies permitting multiple organ transplants, new therapies for allergic diseases, and immunostimulatory therapies for cancer and infectious diseases.

All of these advances have been detailed in Smith's book, “Molecular Immunity: A Chronology of 60-Years of Discovery”, published in 2018.

Now, in 2023 Smith has published a memoir, "The Interleukin Revolution", which introduces molecular immunity to everyone, describing the wonder and excitement of how his discoveries were made and how these discoveries have changed immunology and medicine.