Why AI Is 'Not Particularly Good' at Curing Disease (Plus: The Next GLP-1 Boom and Why America Hates Big Pharma)

One way to tell the story of human history is to watch how we die. At the scale of millennia, the most deadly disease was likely smallpox. Some scientists estimate that it killed billions of people before its cure was summoned from a barn animal. In the 1790s, a British physician named Edward Jenner took material from a cow infected with cowpox and used it to inoculate a young boy. Since that fortunate but deeply unethical science experiment, vaccination—the word coming from the Latin for cow, vacca—has spared hundreds of millions of people from an early death. By the early 1900s, in rich countries like the US where smallpox was on the wane, another killer emerged as the apex predator of humanity: bacterial infection. According to the best records we have, almost all of the top causes of death in the late 19th century were bacterial, whether it was gunky stuff in your lungs or bugs in your gut. But thanks to the accidental discovery of penicillin in the 1920s, and a heroic effort by the United States to scale up the drug during World War II, bacterial infections have plummeted. Today the top causes of death in the U.S. are not poxes or bacteria. They are heart disease, cancer, stroke, and Alzheimer’s. While we have made some progress against this new class of villain—statins for our hearts, immunotherapy for cancer—they are still killing us with remarkable frequency. There is an idea in progress studies called the burden of knowledge. Sometimes it looks like progress in a field like medical science is slowing down, not because we’re getting dumber over time, but ironically because we’re getting smarter. Every time we solve a problem in medicine, it’s like plucking a fruit from a tree. If you pick all the low-hanging fruit, what you’re left with is the taller challenge. One of the tallest challenges for medicine in the last few decades has been dealing with the complications of obesity. Americans who overeat are at a higher risk of a number of illnesses and discomforts: inflammation, cancer, knee pain, sleep apnea. But for a long time, we didn’t have a reliable technology to help people eat less in an environment of food abundance. Science needed new fruits to pluck. But first we needed a taller ladder. That ladder is the GLP-1 drug revolution, which shows no signs of slowing down. In December 2025, Eli Lilly, the most valuable pharmaceutical company in the world, released results for a late-stage trial of retatrutide, its next-generation GLP-1 drug. Unlike initial drugs in this class, retatrutide targets not one hormone (like Ozempic) or two (like Zepbound) but three. The weight-loss effects were historic: Patients lost an average of 29 percent of their body weight over roughly 68 weeks and saw huge improvements in knee pain. The anticipation of retatrutide borders on the rapturous: In a recent podcast interview, the scientist and health influencer Andrew Huberman called retatrutide the protein that will “change everything.” But this is a strange moment for the pharmaceutical industry. In Gallup surveys, Americans rate the drug industry less positively than every other business sector. On the right, the “Make America Healthy Again” movement has gained traction with a broad suspicion of therapies and health authorities, along with a taste for alternative, “do your own research” medicine. Meanwhile, AI boosters often excuse the technology’s downsides by reminding doubters that it will one day “cure cancer.” But I’ve never heard a particularly detailed explanation of how that might even happen. To understand more about the GLP-1 drug revolution, the promise (or over-promise) of AI in medicine, and the roots of public distrust of pharma, I recently spoke to Dave Ricks, the chief executive of Eli Lilly. The following transcript has been edited for clarity, brevity, and the goal of making both speakers sound a bit smarter1. Derek Thompson: Eli Lilly is the largest pharmaceutical company in the world, mostly because of your GLP-1 drugs. Twenty years ago, Lilly helped launch the first approved GLP-1 drug. I’d like you to tell that story from wherever you’d like to start: 2005, the 1970s, the dawn of man. How did this drug category get kicked off? David Ricks: The real first scientific breakthrough that happened was in the early 1970s. There were several papers that looked at something called “the incretin effect.” Incretins are a class of hormones or proteins that your gut excretes, like GLP-1. They noticed that if you ingested food orally versus intravenously, your gut signaled to the rest of your body that you’d eaten something [and released insulin to reduce blood sugar]. But if you took the same food intravenously, blood glucose would spike and stay up. The hypothesis was that some protein in the gut was signaling to the body that you’d eaten. The first protein we identified was actually GIP, which is now the backbone of tirzepatide or Zepbound, our best-selling drug. The companies that worked on this in the 1970s and 1980s included Eli Lilly and Novo Nordisk, the maker of Ozempic. You could ask, “Well, why in the ‘70s didn’t you just make this drug then if you knew about this?” The answer is that peptide chemistry wasn’t very mature. If you give humans native GLP-1 or GIP, they both have a half-life in your body of seven or eight minutes. So it wouldn’t be a very convenient drug. You’d have to walk around with an IV bag all day. A key breakthrough came from the Gila monster study in the late 1980s. John Eng, a doctor in the Bronx, was interested in why certain animals didn’t need to eat very often. He identified that Gila monsters have a mimic of the human peptide GLP-1 that the lizard uses [to stay full]. The Gila monster protein could go about 8 to 10 hours. So you could make a twice-a-day shot. That barely cleared the hurdle of good enough to be a drug. We made it into a drug along with a partner, Amylin, which launched it in 2006. Thompson: Your story stopped in 2006 with the first version of this drug, which was used for type-2 diabetes. How long did it take Lilly to recognize that what had begun as a type-2 diabetes drug was in fact an incredibly powerful weight loss drug? Ricks: When you look on the cover of our annual report from that year, there’s a patient, Maria, and she’s talking about her experience with Byetta, the brand name for exenatide, and she says, “It’s controlling her blood sugar and that her friends notice she’s losing some weight.” There it was like sitting there in April 2007, when we put out that annual report. We were doing studies. But we had a problem. The problem was the side effects associated with GLP-1 drugs are what we call peak to trough, the difference between the highest amount of drug and the lowest. Twice a day dosing [was causing] a lot of GI distress. You’ve about nausea, diarrhea, vomiting. The more we push the dose up, the more we ran into these things with that particular drug. We stopped because it was very unpleasant to take, and the weight loss effects were there but more modest. What started the weight loss part was our ability to get dosing levels up. The incretin system—GLP-1, GIP, and coming soon glucagon—is being boosted in people with regular levels. People aren’t deficient necessarily in these hormones, like GLP-1. We’re boosting them to a super-normal level and it suppresses appetite and kicks up metabolism. To do that, you need to get to higher levels. We produced a once weekly GLP-1 in 2014 called Trulicity. Anyone who was in the diabetes world would know that. Very few people in the lay media would remember that drug, although it was our best-selling drug at one time. With a trick of protein engineering, we made that drug last a week, and people lost more weight. Our competitor, Novo Nordisk, then did a similar trick and made a weekly that launched in 2017 called Ozempic. That only got so famous when they took the chance to study that at an even higher dose in people who had obesity but not dia…