$3M Breakthrough Prize honors duo whose work changed SCD treatment
Researchers made discoveries that led to now-approved gene therapy
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One of the $3 million 2026 Breakthrough Prizes — in Life Sciences — has been awarded to two researchers whose discoveries reshaped the treatment of sickle cell disease (SCD).
The award from the Breakthrough Prize Foundation, which counts its mission as “honoring scientists as heroes of our society,” is shared by Stuart H. Orkin, MD, an investigator at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts, and Swee Lay Thein, a hematologist and clinical investigator who serves as the chief of the sickle cell branch of the National Heart, Lung and Blood Institute in Maryland.
The two researchers were recognized for unraveling how the body switches from fetal to adult hemoglobin and for showing that process could be targeted to treat SCD and beta-thalassemia, a related blood disorder. Hemoglobin is the protein that red blood cells use to transport oxygen throughout the body. Their work laid the foundation for the development of gene therapy for SCD.
“All of us who are physician-scientists want to see our work translated,” Orkin, also the David G. Nathan distinguished professor of pediatrics at Harvard Medical School, said in a press release from the Dana-Farber Cancer Institute that detailed his research.
“The most gratifying part of what we do is seeing the science actually reach patients and benefit patients,” Orkin said.
The Breakthrough Prizes recognize major advances in life sciences, physics, and mathematics. This year’s laureates were honored at a gala in Los Angeles, with a total of six awards, carrying $18 million in prize money altogether.
The Breakthrough Prizes are popularly called the “Oscars of Science,” according to a foundation press release announcing the 2026 awards.
“This year’s laureates show what great science can do — deepen our understanding of the world and lead to discoveries that improve millions of lives,” said Mark Zuckerberg and Priscilla Chan, MD, two of the foundation’s cofounders. “We’re proud to recognize their work.”
Researchers’ work focused on fetal hemoglobin
SCD is caused by mutations in the beta-globin (HBB) gene that lead to the production of an abnormal version of a subunit of the hemoglobin protein that is prone to form clumps. These clumps deform red blood cells into a sickle shape that causes the cells to be destroyed prematurely and to block blood vessels, causing painful episodes known as vaso-occlusive crises (VOCs).
Before birth, babies produce fetal hemoglobin (HbF), which carries oxygen more efficiently than adult hemoglobin. During infancy, the body switches from producing fetal to adult hemoglobin. That’s why SCD symptoms begin only after birth.
Researchers had long known that people with higher HbF levels often have milder SCD, but for many years the molecular switch behind that change remained unclear.
The prize recognized how Thein and Orkin helped solve that puzzle in complementary ways. By mapping the trait for persistent HbF to chromosome 2, Thein successfully pinpointed BCL11A as the critical gene driving this process.
Orkin then showed that BCL11A acts as the main repressor, or off switch, for the production of HbF after birth. His work also showed that inactivating this gene in mice restored HbF production and eliminated SCD symptoms. Further, his lab identified a specific DNA region in the BCL11A gene that regulates its activity only in red blood cells.
Discoveries laid groundwork for developing Casgevey
These findings led to the development of Casgevy (exagamglogene autotemcel), a one-time gene therapy that uses the CRISPR/Cas9 gene-editing tool to disrupt that DNA region in patients’ blood stem cells. This reduces BCL11A’s suppressive effects on HbF production. The gene therapy is approved for SCD patients with VOCs and certain people with beta-thalassemia.
“For us, the long arc of discovery has really come full circle,” Orkin said. “I started at a time when we could not clone genes, and now we can treat patients through gene modification and see them well.”
Casgevy has been shown to help severe SCD patients become free from VOCs and have better quality of life.
“For the sickle cell patients, they no longer have crises, pain crises,” Orkin said. “After therapy, they’re now having a totally new future. And so, it really is transformative.”
Some experimental therapies now in development for SCD, including risto-cel and pociredir, are also focused on restoring HbF production.
The Breakthrough Prize Foundation’s award program is now in its 14th year.
“The brilliant scientists who win the Breakthrough Prize … are building a cathedral of knowledge on foundations laid down by the giants who came before them,” said Yuri Milner, a foundation cofounder. “We owe our civilization — and its future — to them.”
