In February 2025 doctors at the Children’s Hospital of Philadelphia used gene editing to treat a child with carbamoyl phosphate synthetase 1 deficiency, a disorder that lets ammonia build up in the blood. This episode traces the tool back to 1987, when Yoshizumi Ishino’s team in Japan found strange repeating palindromic DNA in E. coli. In 1993 Dick van Soolingen used the repeats to tell tuberculosis strains apart, and Francisco Mojica found them in salt loving archaea and 20 species of microbes. In 2001 Mojica and Ruud Jansen named them CRISPR.

In 2005 three groups found that the spacers between the repeats matched viral DNA, suggesting bacteria had an adaptive immune system, and all three papers were first rejected. Rodolphe Barrangou proved it with yogurt bacteria. The episode explains how Cas1 and Cas2 file new spacers at the front of the array and how the PAM sequence keeps the system from cutting itself. In 2012 Emmanuelle Charpentier and Jennifer Doudna fused two RNAs into a single guide, work that won the 2020 Nobel Prize in Chemistry.

• Why a palindromic DNA sequence folds into a hairpin
• Cas9’s blunt cut versus the staggered sticky ends of Cas12a
• How Cas13’s collateral cutting powers the SHERLOCK diagnostic test
• The 2015 embryo experiments using tripronuclear zygotes that could never develop
• A 2026 shift to Cas12a enzymes guided by sturdier DNA instead of fragile RNA