Finding the fetal hemoglobin switch that Casgevy edits wins five scientists the 2026 Alpert Prize

Casgevy does not correct the sickle mutation. It restarts fetal hemoglobin, an approach Orkin compared with correctional gene therapy and defended on several counts, starting with the validation Casgevy itself now provides ^[8][2]. He described BCL11A's control of globin transcription as "going to the thermostat" ^[11]. Lyfgenia, a beta-globin gene therapy, was approved in the same month as Casgevy, December 2023 ^[9].

The experiment I would single out was done in mice. Jian Xu's 2011 knockout was informative because it was restricted to the red-cell lineage ^[10]. Deleting Bcl11a only where hemoglobin is made tested whether that step alone could rescue sickle red cells, and in that model it did ^[10]. GEN's account says the work validated BCL11A as a therapeutic target in humans ^[10]. A mouse study can support that claim. The test in people came with Casgevy itself, whose results Orkin called "spectacular... remarkable, transformative" ^[1]. Approval came 12 years after the mouse result ^[25].

Daley opened the symposium by paying tribute to Watson. "The mechanism behind the switch would remain an enigma for decades," he said ^[6]. Her 1948 observation came 75 years before the approval ^[24]. Orkin's own part covers at least 33 of those years: his first Alpert prize, in 1993, was for a complete molecular genetic description of thalassemia ^[12]. "A lot has happened in 33 years," he said ^[13]. Daley said the five honorees had "distinct and complementary roles" ^[23]. In my view the prize credits the right step. Doudna, whose team did the initial development of CRISPR-Cas9 gene editing, said in her keynote, "Drug success requires a deep understanding of biology" ^[22][14].

Doudna also gave the uptake figures. She said more than 90 percent of US sickle cell patients qualify for reimbursement coverage for Casgevy ^[16]. Qualifying for coverage is not the same count as receiving the edit. Her other figure, more than 500 patients worldwide, counts people who have begun treatment ^[17]. The account does not say how many finished, how they fared, or how many people are eligible, so 500 cannot be read as a share of anything ^[17].

She listed what still stands in the way: conditioning toxicity, cost, infrastructure and global access ^[18]. "How do we get from one CRISPR therapeutic to CRISPR-for-many? I think it's achievable," she said, citing the 2025 Baby KJ case ^[19]. She said in vivo editing would be critical in future and pointed to two preprints from her lab, NANITE and JET, as works in progress ^[20]. Daley had opened the day with a similar demand: "We should hustle to make therapies that are simpler, safer and scalable" ^[21].