Quote · The Peter Attia Drive
#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcare
Where this was said
The discovery of CRISPR: from salt flats to gene editing and genetic medicine
At 45:30 · chapter starts 37:15
In the late 1980s, Francisco Mojica was doing his PhD at the University of Alicante, studying salt-tolerant archaea in the evaporative salt flats of Santa Pola on Spain's Mediterranean coast. His original project was scooped before publication, so he turned to a puzzling feature he kept noticing in the genome: clusters of short, regularly spaced palindromic repeats separated by unique spacer sequences. Nobody knew what they were. Mojica spent the entire 1990s and into the early 2000s trying to find out — with almost no institutional support and growing risk of being scooped. The breakthrough came in 2003 when he used the BLAST database to compare the spacer sequences against all sequenced genomes and found that they exactly matched DNA from bacteriophages — viruses that infect bacteria. [1] — Peter Attia "CRISPR paper rejected by 4 top journals: Francisco Mojica's landmark paper describing CRISPR as a bacterial adaptive immune system was reje…" 41:20 The spacers were memories. The repeats were the index of past infections. The organism had vaccinated itself against future phage attacks by storing fragments of the enemy's genome. This was an adaptive immune system in the simplest organisms in biology. Mojica's paper was rejected by Nature, PNAS, Molecular Microbiology, and Nucleic Acids Research before finally appearing in the Journal of Molecular Evolution in February 2005. From there the field accelerated rapidly: a 2007 Danisco paper validated CRISPR's immune function and identified Cas9; in 2012, Doudna, Charpentier, and Feng Zhang's group showed you could program the system with a custom guide RNA to cut DNA anywhere in any genome, and incorporate new sequences at the cut site. In December 2023, the FDA approved Casgevy, the first CRISPR-based therapy, for sickle cell disease. [2] — Peter Attia "First CRISPR therapy FDA approved Dec 2023: In December 2023, the FDA approved Casgevy, the first CRISPR-based therapy in clinical use, ind…" 44:10 Bacteria invented CRISPR 3 billion years ago. Mojica just noticed it.
Francisco Mojica's landmark paper describing CRISPR as a bacterial adaptive immune system was rejected by Nature, PNAS, Molecular Microbiology, and Nucleic Acids Research before finally being published in 2005.
In December 2023, the FDA approved Casgevy, the first CRISPR-based therapy in clinical use, indicated for sickle cell disease.
John Eng at the Bronx VA Medical Center ordered dried Gila monster venom out of curiosity about pancreatic biology. He found Exendin-4, a peptide with 53% similarity to human GLP-1, a half-life of hours instead of minutes, and resistance to DPP-4 degradation. The result, eventually, was the entire GLP-1 receptor agonist drug class.
