#401 ‒ How curiosity transforms medicine: extraordinary discoveries that changed modern healthcare

Full analysis

Peter Attia spends an hour tracing five landmark drug classes — statins, ACE inhibitors, PCR-based diagnostics, CRISPR gene editing, and GLP-1 drugs — back to their unexpected origins in jellyfish, fungi, snake venom, hot-spring microbes, salt-pond bacteria, and a Gila monster. The through-line is a policy argument: curiosity-driven basic science that looks medically irrelevant at the time is often the irreplaceable foundation of therapies that save millions of lives, and funding systems that demand near-term clinical payoff systematically miss it.

What was covered

• Green fluorescent protein (GFP): Osamu Shimomura spent 19 summers (1961–1988) cutting the bells off roughly 850,000 jellyfish at Friday Harbor, Washington to understand bioluminescence. The protein he isolated, GFP, sat mostly ignored for 30 years before Martin Chalfie (Columbia) and Roger Tsien (UCSD) turned it into the universal cellular labeling tool that now underpins drug development pipelines, cancer research, and neuroscience worldwide. Shimomura, Chalfi, and Tsien shared the 2008 Nobel Prize in Chemistry.

• Statins: In the late 1960s, Akira Endo at Sankyo reasoned that fungi — locked in chemical warfare with bacteria for hundreds of millions of years — must have already evolved a molecule that blocks the cholesterol synthesis enzyme HMG-CoA reductase. After screening more than 6,000 microbial strains over two years, his team found the hit in 1972: a mold growing on a rice sample from a grain shop in Kyoto. Merck then isolated a related compound, lovastatin, approved in the United States in 1987. Lovastatin begat simvastatin, pravastatin, atorvastatin, rosuvastatin — the entire statin class.

• ACE inhibitors: Brazilian pit viper venom, stockpiled at the Butantan Institute for public health reasons, led pharmacologist Mauricio Rocha e Silva to discover bradykinin in the late 1940s. His graduate student Sérgio Ferreira then found peptides in the venom (bradykinin-potentiating factors, BPFs) that preserved bradykinin by blocking its breakdown. Working in London with fellow postdoc Kevin Inge, Ferreira found that the same enzyme both destroyed bradykinin and converted angiotensin I to the vasoconstrictor angiotensin II — angiotensin-converting enzyme, ACE. Squibb chemists used the smallest active venom peptide as a structural template to design captopril, approved by the FDA in 1981 as the first oral ACE inhibitor. The class — captopril, enalapril, lisinopril, ramipril — and the related angiotensin-receptor blockers (losartan, valsartan) are now among the most widely prescribed drugs in existence, used for hypertension, heart failure, chronic kidney disease, and post-heart-attack care.

• PCR: In 1969, microbiologist Thomas Brock and undergraduate Hudson Freese published a paper characterizing Thermus aquaticus, a bacterium living in 88°C springs in Yellowstone. In 1983, biochemist Kary Mullis at Cetus conceived of polymerase chain reaction (PCR) — the technique for copying any DNA sequence exponentially — but the E. coli enzymes then in use fell apart at the high temperatures required each cycle. The Cetus team solved this by using the heat-stable TAQ polymerase from Brock's Yellowstone organism. Mullis won the 1993 Nobel Prize in Chemistry. Attia argues PCR is not just a drug but the enabling technology for essentially all of modern molecular biology: genetic testing, forensic analysis, cancer mutation panels, prenatal screening, vaccine development, genomics, and gene therapy.

• CRISPR: Spanish microbiologist Francisco Mojica, studying salt-flat archaea near Alicante in the late 1980s and throughout the 1990s, noticed clusters of short, regularly spaced palindromic repeats in their genomes. In 2003 he matched the spacer sequences against public databases and found they corresponded to fragments of bacteriophage DNA — evidence that bacteria maintain an adaptive immune memory of past viral infections. The paper was rejected by Nature, PNAS, Molecular Microbiology, and Nucleic Acids Research before appearing in the Journal of Molecular Evolution in February 2005. Danisco (the yogurt company) provided direct experimental confirmation in 2007 and identified Cas9. In 2012, Jennifer Doudna and Emmanuelle Charpentier demonstrated programmable genome editing; they shared the 2020 Nobel Prize in Chemistry. In December 2023 the FDA approved Casgevy, the first CRISPR-based therapy, for sickle cell disease. A phase 1b trial for familial hypercholesterolemia — a genetic disorder causing severely elevated LDL — has shown early promising results.

• GLP-1 receptor agonists: In the late 1980s, John Eng, a clinical endocrinologist at the Bronx VA, read that Gila monster venom caused dramatic pancreatic inflammation in bitten animals and that the lizard maintains stable blood sugar despite eating only three or four times a year. Working in Rosalyn Yalow's lab (Yalow won the Nobel for inventing the radioimmunoassay), Eng isolated a new peptide from the venom in 1993 — exendin-4 — which showed 53% amino acid similarity to human GLP-1 (glucagon-like peptide-1), the gut hormone that triggers insulin secretion after meals. Unlike native GLP-1, which is destroyed by the enzyme DPP-4 within about two minutes, exendin-4 resists DPP-4 and has a half-life of hours. The VA declined to patent it; Eng patented it himself. Eli Lilly and Amylin brought synthetic exendin-4 to market in 2005 as Byetta (exenatide), the first GLP-1 receptor agonist. Subsequent drugs — liraglutide, semaglutide, and tirzepatide (which adds GIP agonism) — are now reshaping treatment of type 2 diabetes, obesity, and, through cardiovascular outcomes data, atherosclerotic risk. Trials are ongoing in heart failure, kidney disease, sleep apnea, alcohol use disorder, and Alzheimer's disease.

Notable claims & predictions

• Peter Attia: "There is essentially no significant area of modern biology that isn't touched somewhere in its toolkit by a protein that came out of a jellyfish." (GFP is in active use in virtually every major biology and biomedical research lab in the world.)

• Peter Attia on statins: "The entire class of drugs that by any reasonable estimate has prevented millions of cardiovascular events and millions of premature deaths" traces to a mold on a piece of rice in a Kyoto grain shop.

• Peter Attia on ACE inhibitors: The renin-angiotensin-aldosterone system "is now one of the most heavily drugged pathways in all of medicine" and these drugs are "plausibly among the most consequential drug classes ever developed" — all tracing to Brazilian pit viper venom collected for public health, not drug discovery.

• Peter Attia on PCR: "Without that 1969 paper, modern biology as it exists today simply could not exist. There's no plausible alternative history in which we get to where we are without somebody somewhere going to look in the boiling water for life."

• Peter Attia on funding: Douglas Prasher, who cloned the GFP gene, "could not get NIH to fund him to continue. The system failed in exactly the way I'm describing." The argument: grant panels that demand near-term translational impact — asking 'what disease will this cure?' — would have defunded the origins of statins, ACE inhibitors, PCR, CRISPR, and GLP-1 drugs. "We are demonstrably terrible at predicting which one of them is going to change everything."

• Peter Attia on GLP-1 drugs: "These drugs are reshaping medicine in real time" — with ongoing trials in heart failure, kidney disease, sleep apnea, alcohol use disorder, and possibly Alzheimer's disease, though "we don't yet know how broad the indication space will turn out to be."

Fact check

The episode is a historical narrative rather than a collection of quantitative health claims, so most assertions are historical and well-documented.