May 5, 2026

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How scientists made the discoveries behind a game-changing gene therapy for sickle cell disease

Stuart Orkin and Swee Lay Thein shared a Breakthrough Prize in Life Sciences for their research on genetic causes of sickle cell disease and beta-thalassemia that set the stage for approved gene therapies. The treatments are not accessible to everyone, though

By Tanya Lewis edited by Jeanna Bryner

Artwork showing normal red blood cells (round), and red blood cells affected by sickle cell disease (crescent shaped).

KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty Images

Sickle cell disease is the scourge a person’s red blood cells. The inherited blood disorder, which disproportionately affects people in sub-Saharan Africa and India, can cause unbearable pain “crises” and extreme exhaustion. And until recently, there was no curative treatment. Now approved gene therapies for sickle cell disease (including sickle cell anemia, the most extreme form) and its milder cousin, beta-thalassemia, show enormous promise.

The therapies work by deactivating or replacing a hemoglobin gene so that a person’s body makes a healthy form instead of the telltale sickle-shaped red blood cells that define sickle cell disease or averting the red blood cell deficiency that causes beta-thalassemia.

At some point, all humans produce two forms of hemoglobin, the red blood cell protein that binds oxygen so it can be transported throughout the body: a fetal form, which is more efficient at extracting oxygen in the womb, and an adult form. After we’re born, our body switches from producing the fetal form to making the adult form.

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After years of research, scientists figured out that by turning off BCL11A—a gene known to suppress fetal hemoglobin production—they could coax the body of a person with sickle cell disease to continue making healthy hemoglobin. Companies have now developed gene therapies that target this gene. In clinical trials, people who received the treatment were functionally cured of their condition—those with sickle cell disease saw a complete resolution of their pain during the study period, and those with beta-thalassemia didn’t need blood transfusions or bone marrow transplants.

On April 18 a Breakthrough Prize in Life Sciences—one of the $3-million Breakthrough Prizes, sometimes referred to as the “Oscars of science”—was awarded to Swee Lay Thein and Stuart Orkin, who led efforts to identify the BCL11A gene and to show that shutting it off could restore healthy hemoglobin production, setting the stage for treating these devastating blood diseases.

Scientific American spoke separately with Orkin, a professor of pediatrics at Harvard Medical School and an investigator at the Dana-Farber Cancer Institute and Boston Children’s Hospital, and Thein, a senior investigator at the National Institutes of Health about what happened in the work that led to their prize and how these treatments can be made more accessible to the people who stand to benefit the most.

[An edited transcript of the interviews follows.]

How did you come to study sickle cell disease? And did you realize early on that fetal hemoglobin would be a good therapy target?

ORKIN: I started out in the 1980s working on the genetics of [beta-thalassemia]—that is, what mutations lead to the deficiency of hemoglobin in that disorder. The hope was that we would learn how a red [blood] cell is made and how genes are regulated. We didn’t really learn that, but we learned a lot about mutations and disease. Even prior to that, we knew the deficiency of beta-globin [a component of the adult hemoglobin protein] in [beta-thalassemia] and the [effects of a] mutation in sickle cell disease can be alleviated by expressing more fetal hemoglobin.

We knew that, from family studies in some very rare individuals who had a lot of fetal hemoglobin, if you raise the level of fetal hemoglobin high enough, you can basically ameliorate those disorders—plus, fetal hemoglobin is perfectly fine to substitute for adult hemoglobin [for carrying oxygen]. As early as genes were cloned back in the early 1980s, one of the goals was to see if we could reverse the switch and make fetal hemoglobin expressed at a high level in adult cells as a treatment [for beta-thalassemia]. The problem was, we didn’t understand the process at all—that’s what’s consumed the past 15 to 20 years or research—or how to reverse it.

Why do our cells switch from making fetal to adult hemoglobin in the first place?

ORKIN: We do that because, in utero, having a feta