2020 Harrington Prize awarded to Dr. Stuart H. Orkin
April 16, 2020
Harrington Discovery Institute and The American Society for Clinical Investigation honor Dr. Orkin for his contributions to red blood cell biology
The seventh annual Harrington Prize for Innovation in Medicine has been awarded to Stuart
H. Orkin, MD, of Dana-Farber/Boston Children’s Cancer and Blood
Disorders Center, a David G. Nathan Professor of Pediatrics at Harvard Medical
School, and an Investigator at the Howard Hughes Medical Institute.
Harrington Prize for Innovation in Medicine, established in 2014 by the
Institute at University Hospitals in Cleveland, Ohio, 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.
Orkin is being recognized 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.
cell disease (SCD), which was called the first molecular disease by Linus
Pauling in 1949, is due to a mutation in the DNA encoding the beta-globin chain
of hemoglobin, the molecule in red blood cells that carries oxygen and delivers
it to tissues. In SCD, normal disc-like red blood cells become rigid and sickle
shaped due to abnormal polymerization of sickle hemoglobin. Red cells get stuck
in small blood vessels, thereby cutting off blood flow and leading to tissue
damage and intense pain (a “sickle crisis”). SCD affects about 75,000 in the U.S.
and millions of people throughout the world.
SCD the adult form of hemoglobin is affected. A fetal form of hemoglobin, which
is shut-off shortly after birth, is normal. Dr. Orkin discovered how the switch
between fetal and adult hemoglobin is controlled, solving a longstanding
mystery and suggesting new ways to reactivate normal fetal hemoglobin. Specifically,
the Orkin laboratory showed that the gene BCL11A turns off fetal hemoglobin. By
blocking BCL11A, fetal hemoglobin expression can be restored in the adult, offering
a potential cure. In genetically engineered SCD mice, removal of BCL11A corrected
red blood cell production. At Boston Children’s Hospital, Dr. Orkin’s colleague,
David A. Williams, MD, has translated these findings to patients in a gene
therapy trial in which BCL11A expression is blocked. Dramatic clinical results
in the first patients have validated BCL11A as a target for therapy. Promising preliminary
findings of company-sponsored gene editing trials with BCL11A as a target have
also been reported.
sickle cell community has been energized by this discovery, which is a complete
game-changer for a large group of people living with SCD. Dr. Orkin’s work has
paved the way for testing a gene therapy approach, and potentially other
approaches, to treat this debilitating disease,” said W. Kimryn Rathmell, MD,
PhD, Interim Chair, Department of Medicine at Vanderbilt University School of
Medicine, Cornelius Abernathy Craig Professor of Medicine, and 2019-2020
President of the ASCI.
Orkin is an extraordinary investigator and a dominant force in the fields of
hematology and genetic disease. His discovery of BCL11A as a master regulator
of hemoglobin gene switching, and his pursuit of application in sickle cell
disease, is a prime example of how fundamental discovery can be leveraged for
clinical impact,” said Jonathan S. Stamler, MD, President, Harrington Discovery
Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished
Chair of Cardiovascular Innovation at University Hospitals and Case Western
Reserve University School of Medicine.
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 2020 recipient.
In addition to
receiving a $20,000 honorarium, the Harrington Prize recipient delivers The
Harrington Prize Lecture at the AAP/ASCI/APSA Joint Meeting, publishes an essay
in the Journal of Clinical Investigation, and speaks at the Harrington
Scientific Symposium in Cleveland.
Dr. Orkin is the David G. Nathan Distinguished
Professor of Pediatrics at Harvard Medical School, and an Investigator of the
Howard Hughes Medical Institute. He is a principal faculty member of the
Harvard Stem Cell Institute and an associate of the Broad Institute of
MIT/Harvard. He received his BS from MIT and MD from Harvard Medical School. He
completed pediatric hematology/oncology training at Boston Children’s Hospital
and the Dana-Farber Cancer Institute, and trained in the laboratory of the late
Philip Leder at the National Institutes of Health.
first recipient of The Harrington Prize for Innovation in Medicine, in 2014,
was Dr. Harry Dietz (Johns Hopkins University School of Medicine, USA), for his
contributions to the understanding of the biology and treatment of Marfan
syndrome, a disorder leading to deadly aneurysms in children and adults. The
2015 recipient was Douglas R. Lowy, MD, Chief, Laboratory of Cellular Oncology
(The National Cancer Institute, USA), in recognition of his discoveries that
led to the development of the Human Papillomavirus vaccine to prevent cervical
cancer. The 2016 recipient was Jeffrey M. Friedman, MD, PhD (The Rockefeller
University, USA), for his discovery of leptin, which controls feeding behavior
and is used to treat related clinical disorders. In 2017, the Prize was awarded
jointly to Daniel J. Drucker, MD (Mount Sinai Hospital, Canada), Joel F.
Habener, MD (Massachusetts General Hospital, USA) 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. The 2018 recipient was Helen H.
Hobbs, MD (UT Southwestern Medical Center, USA), for her discovery of the link
between a gene mutation (PCSK9) and lower levels of LDL, which has improved the
treatment of high cholesterol. In 2019, Dr. Carl H. June, MD, received the
award for advancing the clinical application of CAR T-cell therapy for cancer
treatment, and for his sustained contributions to the field of cellular
American Society for Clinical Investigation
Founded in 1908, the American Society for Clinical
Investigation is one of the oldest and most esteemed nonprofit honor societies
of physician-scientists. Membership is by election only, and only researchers
who are 50 years of age or younger are eligible for nomination to the Society.
Therefore, membership in the ASCI is a recognition of a researcher’s
significant contributions, at a relatively young age, to the understanding of
human disease. The Society counts among its ranks more than 3,000 members, many
of whom are leaders in academic medicine and industry. Many members have been
recognized by election to the U.S. National Academy of Sciences and the U.S.
National Academy of Medicine. The ASCI is also proud to have among its
membership winners of the Nobel Prize and the Lasker Award. The ASCI convenes
an annual meeting with the Association of American Physicians, and the Society
self-publishes the prestigious Journal of Clinical Investigation (founded in 1924), and JCI Insight (founded in 2016).
Harrington Discovery Institute at University Hospitals in Cleveland, Ohio – 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’.
Harrington Project for Discovery & Development
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.