dr. Stuart Orkin didn’t set out to develop a landmark treatment for sickle cell anemia 45 years ago when he decided to study how blood cells were formed. He became a researcher at Harvard Medical School just as scientists were learning how to clone, or make copies of, genes. “Everyone was talking about how we could solve genetic diseases,” he says. “But no one had any idea what that really meant; “It was kind of a Disney fantasy.” Orkin focused his attention on the hemoglobin gene, which is mutated in people with sickle cell anemia and another set of blood diseases called beta thalassemia. Understanding how these diseases work could make them good candidates for genetic-based therapy, if that happens.
Almost half a century later, it finally happened thanks to CRISPR gene editing technology. The U.S. Food and Drug Administration approved the first gene therapy using CRISPR to treat sickle cells in December 2023. The therapy involves reactivating a person’s ability to produce a healthy form of hemoglobin, called fetal hemoglobin, since they were babies. A bone marrow transplant is required to remove diseased blood cells, edit them in a laboratory to activate the fetal form of hemoglobin, and return them to the patient’s body. Basically, the procedure can be a cure for many people, freeing them from painful episodes of sickle cell anemia and frequent blood transfusions, and the life-changing treatment is based on Orkin’s research that identifies the genes that regulate hemoglobin fetal.
But Orkin, a professor of pediatrics at Harvard Medical School, isn’t resting on his laurels. The procedure is expensive, invasive and out of reach for most of the 20 million people with sickle cell anemia worldwide. He is now trying to find a way to trigger fetal hemoglobin production with a pill, an ambitious task. But he doesn’t let himself be deterred. “The question now is, ‘What’s the next version of this therapy?’” he says. “We haven’t really solved the problem we set out to solve, which is how to make a lot of people better. “That’s what we’re working on now.”