Tree of Hope, Remain Strong (1946) by Frida Kahlo
First attempts in a new field of medicine rarely go according to plan. On September 14, 1990, Dr. William French Anderson and his team at the National Institute of Health (NIH) performed the first official gene therapy trial. The patient, a 4-year-old Ashanti deSilva, suffered from a rare genetic disease called adenosine deaminase (ADA) deficiency, a form of severe combined immune deficiency (SCID). Children with ADA-SCID rarely make it to adulthood; the lack of a functional immune system makes any illness potentially lethal. To make up for the deficiency of this crucial enzyme, Ashanti had been receiving ADA injections since she was two, but the effectiveness of this treatment usually declines fairly quickly, and by age four, she was no longer responding to it.
Ashanti’s parents, Raj and Van DeSilva, felt like they had run out of options for their daughter. They put all their hopes on this trial. Anderson and his team extracted white blood cells from Ashanti’s body, inserted a functional copy of the ADA gene into these cells using a retroviral vector, and then infused the genetically modified cells back into her body. Remarkably, this worked. Ashanti’s immune system function improved over the next few months; her T-cell count rose dramatically, and she no longer constantly fell sick. It was not a one-time cure — she still needed regular infusions every two months to maintain her health — but to her parents her recovery was nothing short of miraculous. Ashanti could begin living a normal life for the first time; going to school, for one, was no longer a life-threatening affair.
Thirty-five years since that first success, a very similar story swept the world. On May 15, 2025, Kyle Junior Muldoon — better known to the world as baby KJ — made headlines after the announcement that he had been successfully treated with the first personalized, CRISPR gene-editing therapy. Just nine months earlier, in August 2024, mere days after birth, KJ was diagnosed with carbamoyl phosphate synthetase 1 (CPS1) deficiency, an extremely rare and often fatal genetic disorder that prevents the body from breaking down ammonia. What followed was an extraordinary race to create a cure just for him: within days, his DNA was sequenced to find the specific mutations (two, in his case) in the CPS1 gene. Then, a cutting-edge base-editing therapy was designed tailored to these mutations. By months four and five, preclinical safety and efficacy testing was underway in mice and monkeys, and by month six, the FDA approved this single-patient product within a week of the application.
After receiving two infusions of his therapy — one in February 2025, and another a month or so later — he quickly began getting healthier. He could tolerate more protein, started gaining weight, needed fewer medications, and could achieve simple, regular baby activities, like sitting upright. On June 3rd, 2025, nine months after he was born, KJ was discharged from the Children’s Hospital of Philadelphia. His parents took him home for the first time.
Kyle Muldoon with his son, KJ. Credits:Chloe Dawson/Children's Hospital of Philadelphia
These two extraordinary stories, three and a half decades apart, share a lot in common: parents grasping onto the last thread of hope for their child, the magical idea of fixing previously untreatable afflictions at the very core, teams working urgently for months to develop a cure, and, ultimately, a chance for a child to live a regular life.
But there are also some key differences that reflect the progress the field of cell and gene therapy has gone through in that time: new technologies, updated regulations, better development speed, safety, and efficacy, and a broader number of target diseases. Ashanti’s trial took two years of rigorous reviews from application to approval; KJ’s took two weeks. Ashanti’s therapy used a retroviral vector to deliver the functional gene, a delivery mechanism that would later be culprit in accidentally inserting genes away from its target (a possibly devastating outcome known as insertional mutagenesis). KJ’s, on the other hand, used lipid nanoparticles — these incredibly minuscule fat-bubble suitcases — to transport mRNA, which is then translated into a base-editor protein that edits — as if correcting a spelling in a word processor — only the specific mutation. Ashanti’s therapy was ex vivo: cells were extracted and modified outside the body; KJ’s therapy was in vivo: his body performed the modifications itself. Ashanti’s therapy was not personalized; the same product was used for all ADA-SCID patients. KJ’s was personalized to his exact mutation.
KJ’s story was celebrated across the world. This incredibly rapid, precise, effective therapeutic future should, after all, imbue a grand sense of excitement. His triumph over impending death is an astonishing demonstration of what 21st century medicine can achieve when cutting-edge science, experienced and compassionate medical staff, and proactive regulators come together, driven with a sense of urgency. These “elite institutions with complementary superpowers” — as Fyodor Urnov, Scientific Director at the Innovative Genomics Institute at UC Berkeley and one of the key characters in the baby KJ success story puts it — gave a boy with almost no hope, and his family, the chance at a regular life.
And yet, this triumph reveals a troubling paradox. We now find ourselves at an inflection point where the science to perform such miracles, to cure rare and even ultra-rare genetic diseases — like spinal muscular atrophy (SMA), hemophilia A, even restoring vision — is not only advancing rapidly but is demonstrably here. Regulatory pathways, like with the rapid approval for baby KJ, have even evolved to support these breakthroughs. But, despite saving many lives, many therapies born from these advances don’t ever get commercialized, and if they do, many are unable to translate into sustainable businesses.
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