March 24, 2021

International Harrington Prize Jointly Awarded to Dr. Warren Leonard and John O'Shea

The eighth annual Harrington Prize for Innovation in Medicine has been jointly awarded to Warren J. Leonard, MD, NHLBI, NIH Distinguished Investigator, and John J. O’Shea, MD, Scientific Director, NIAMS, NIH, for their respective contributions to the field of immunology, from fundamental discovery to therapeutic impact.

The Harrington Prize for Innovation in Medicine, established in 2014 by the Harrington Discovery Institute at University Hospitals and The American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application.

Cytokines, small proteins that modulate lymphocyte (immune cell) behavior, play an important role in the body’s immune response. A major group of cytokines termed interleukins (IL) were discovered in the 1970’s and over 30 family members have been subsequently identified. The discovery of interleukin-2 (IL-2) as central to regulating T- lymphocyte activity was a major advance in the field. This year’s Harrington Prize recognizes two physician-scientists whose individual and collaborative work has provided fundamental insights into IL-2-related biology, led to new diagnostics for human immunodeficiency syndromes, and resulted in a new class of therapeutics for numerous inflammatory and autoimmune disorders.

Dr. Warren Leonard’s discovery of the IL-2 receptor was a major advance in the field. His studies also revealed that one component of this receptor, termed the gamma chain (IL-2Rg), was shared amongst receptors for numerous interleukins, and thus central to signaling within the immune system. Indeed, seminal work by Dr. Leonard in 1993 demonstrated that patients with mutations in IL-2Rg suffered from the immune disorder X- linked severe combined immunodeficiency (XSCID), or “Bubble Boy” disease. Babies born with XSCID have little to no immune protection, making them prone to developing life- threatening infections. Dr. Leonard’s work has also led to new molecular diagnostics in XSCID and paved the way to gene therapy for human XSCID.

Dr. John O’Shea discovered the signaling protein JAK3 and showed that it was essential for the immune actions of interleukins that share IL-2Rg. In collaborative papers in 1994 and 1995, Drs. Leonard and O’Shea demonstrated that JAK3 signals “downstream” of IL-2Rg, leading them to predict and then demonstrate that similar to mutations in IL-2Rg, mutations in JAK3 result in severe combined immunodeficiency. This finding suggested that therapies inhibiting JAK3 activity may dampen the immune system, which is overactive in many diseases. Dr. O’Shea then collaborated with industry to develop an oral JAK inhibitor for rheumatoid arthritis. This work has inspired a new field of JAK inhibitors, referred to as “jakinibs”, which are being evaluated in clinical trials for a wide range of inflammatory and immune diseases.

A committee composed of members of the ASCI Council and the Harrington Discovery Institute Scientific Advisory Board reviewed nominations from leading academic medical centers from four countries before selecting the 2021 Harrington Prize recipients.

“The impact Drs. Leonard and O’Shea have had on the field of immunology is nothing short of extraordinary. Their work spans the full continuum from discovery to bedside and represents precisely the type of advancements the Harrington Prize seeks to recognize,” said Lorraine B. Ware, MD, Professor of Medicine, Vanderbilt University School of Medicine and 2020-2021 President of the ASCI.

“We are pleased to recognize the groundbreaking work of Drs. Leonard and O’Shea. They are exemplary physician-scientists who have moved a field forward and transformed the standard of care. Their work will continue to have therapeutic impact for years to come,” said Jonathan S. Stamler, MD, President, Harrington Discovery Institute, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University.

In addition to receiving a $20,000 honorarium, co-recipients Dr. Leonard and Dr. O’Shea will deliver The Harrington Prize Lecture at the 2021 AAP/ASCI/APSA Joint Meeting, will be featured speakers at the 2021 Harrington Scientific Symposium, and will co-publish an essay in the Journal of Clinical Investigation.

Since its establishment, The Harrington Prize for Innovation in Medicine has recognized outstanding and diverse innovations in medicine:

• 2014: Harry Dietz, MD, Johns Hopkins University, for his contributions to the understanding of the biology and treatment of Marfan syndrome, a disorder leading to deadly aneurysms in children and adults.
• 2015: Douglas R. Lowy, MD, The National Cancer Institute, in recognition of his discoveries that led to the development of the Human Papillomavirus vaccine to prevent cervical cancer.
• 2016: Jeffrey M. Friedman, MD, PhD, The Rockefeller University, for his discovery of leptin, which controls feeding behavior and is used to treat related clinical disorders.
• 2017: Jointly awarded to Daniel J. Drucker, MD, Mount Sinai Hospital, Canada, Joel F. Habener, MD, Massachusetts General Hospital, and Jens J. Holst, MD, DMSc, University of Copenhagen, Denmark, for their discovery of incretin hormones and for the translation of these findings into transformative therapies for major metabolic diseases such as diabetes.
• 2018: Helen H. Hobbs, MD, UT Southwestern Medical Center, for the discovery of the link between a gene mutation (PCSK9) and lower levels of LDL, which has improved the treatment of high cholesterol.
• 2019: Carl H. June, MD, University of Pennsylvania, for advancing the clinical application of CAR T therapy for cancer treatment, and for his sustained contributions to the field of cellular immunology.
• 2020: Stuart H. Orkin, MD, Harvard University, for breakthrough discoveries on red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders.