Gene therapy

Gene therapy entered human medicine at 12:52 p.m. on September 14, 1990, when a four-year-old girl named Ashanti DeSilva received an infusion of her own cells—modified to carry a gene her body couldn't produce. The treatment took place at the NIH Clinical Center in Bethesda, Maryland, culminating decades of research into whether genetic diseases could be cured by adding the missing code.

The adjacent possible required three converging capabilities. Retroviral vectors could insert genes into human cells—scientists had discovered that retroviruses, which naturally integrate into chromosomes, could carry therapeutic payloads. Cell culture techniques allowed T cells to be extracted, modified, and reinfused. And sequencing technology had identified the specific genes responsible for diseases like adenosine deaminase (ADA) deficiency, the condition afflicting DeSilva.

Ashanti DeSilva was diagnosed at 26 months after an almost ceaseless series of infections. She suffered from ADA-SCID—severe combined immunodeficiency caused by a missing enzyme. Without treatment, children with this condition typically die from infections their immune systems cannot fight. W. French Anderson, R. Michael Blaese, and Kenneth Culver at NIH had spent five years developing a retroviral approach, finally gaining approval from the Recombinant DNA Advisory Committee in July 1990 and the FDA in September.

The protocol was grueling: draw blood, culture the T cells, infect them with retroviral vectors carrying functional ADA genes, then reinfuse the modified cells. DeSilva received 11 infusions over two years. The results were remarkable. A child who had spent her life isolated at home saw her T-cell count rise to normal levels within six months. She could attend school. She could have a childhood.

But the treatment wasn't a cure. DeSilva continued receiving enzyme replacement therapy alongside gene therapy, complicating interpretation of the results. Critics debated whether the inserted genes were truly responsible for her improvement. The regulatory path had been brutal—Anderson endured 20 hours of hostile public hearings across a dozen reviews by seven committees.

The cascade from this first trial was slower than hoped. In 1999, an 18-year-old named Jesse Gelsinger died during a gene therapy trial at the University of Pennsylvania, temporarily halting the field. But research continued. By 2017, the FDA approved Kymriah, a gene therapy for leukemia. By 2019, Zolgensma treated spinal muscular atrophy. CRISPR gene editing, emerging in 2012, opened new approaches that avoided some of retroviral therapy's risks.

Ashanti DeSilva lived. She earned a master's degree from Ohio State University and became a genetic counselor—professionally guiding others through the genetic conditions she had survived. Her case proved that human genes could be therapeutically modified. The technology that saved her life eventually enabled treatments for blindness, hemophilia, and sickle cell disease.

By 2026, gene therapy has become a recognized medical category, with dozens of approved treatments and hundreds in clinical trials. The four-year-old who received her modified cells in 1990 demonstrated that the code of life could be edited to heal.