Sickle cell went 113 years from first case report to approved gene-editing treatment

Casgevy does not aim at the mutation it treats. Davies told GEN the therapy works "not by fixing the SCD mutation directly" ^[19]. The disease is a recessive point mutation in the gene for beta-globin ^[2], the one Linus Pauling called "the first molecular disease" in 1949 ^[11]. On that description, the therapy changes a different base from the one that causes the disease ^[23].

The medical literature first described the disease in 1910 ^[3], Pauling attached his label in 1949 ^[11], the first sickle cell patient underwent CRISPR cell therapy in July 2019 ^[6], and the two approvals came in December 2023 ^[1]. That is 113 years from case report to approved therapy ^[20], and 70 from Pauling to the first treated patient ^[21].

For most of that stretch the only effective therapy was hydroxyurea, a generic chemotherapy drug ^[12]. Davies puts the United States patient population at an estimated 100,000 ^[13] and said the community "has been waiting an eternity for something to get excited about" ^[14]. The interview does not include a count of how many people have received Casgevy or Lyfgenia, or a price for either ^[22]. The neglect argument rests on the pre-2023 treatment record and on Davies's own judgement.

He said he found it ironic that CRISPR "should find its first clinical success treating patients with a disease that, many would argue, has been underfunded and forgotten by large sections of the medical and pharma communities" ^[9]. The book's impetus, by his account, came partly from John Evans, CEO of Beam Therapeutics, who described sickle cell in a GEN interview about five years ago as "the most famous genetic mutation in the world" ^[10].

Victoria Gray, treated in 2019, discussed her therapy and recovery in a series of interviews on National Public Radio ^[7]. By going public she "literally inspired other warriors to enroll in the CRISPR trial", Davies said ^[15]; Vertex sponsored it ^[8]. Enrollment in the trial that produced the first clinical success thus depended in part on one participant's willingness to talk, in a population Davies describes as almost exclusively persons of color and as subject to discrimination in the medical system on both sides of the Atlantic ^[18]. Davies said he is "thrilled that she's healthy" and that she now works as a patient advocate ^[16]. He interviewed her in her local church in Mississippi ^[17].