The eighth annual Harrington Prize for Innovation in Medicine is 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 1970s 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. The 2021 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. 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-2Rγ), 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-2Rγ 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. O’Shea discovered the signaling protein JAK3 and showed that it was essential for the immune actions of interleukins that share IL-2Rγ. In collaborative papers in 1994 and 1995, Drs. Leonard and O’Shea demonstrated that JAK3 signals “downstream” of IL-2Rγ, leading them to predict and then demonstrate that similar to mutations in IL-2Rγ, 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.

Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, OH – part of The Harrington Project for Discovery & Development – aims to advance medicine and society by enabling our nation’s most inventive scientists to turn their discoveries into medicines that improve human health. The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a ‘Better World’.

The Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in late February 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines. For more information about The Harrington Project and the Harrington Discovery Institute, visit: HarringtonDiscovery.org.