In the past few years, we've learned that GLP-1 drugs don’t just help with diabetes or increase people’s feelings of fullness to help them lose weight. They have broad effects on substance abuse and behavior. They even seem to help with otherwise incurable illnesses, like Alzheimer's and schizophrenia. This month, a team of scientists studying 2 million patients in the Veterans Affairs medical system found that GLP-1s were associated with “a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders (clotting), cardiometabolic disorders (like strokes and heart attacks), infectious illnesses and several respiratory conditions.”

Today’s guest is a coauthor on the paper, Ziyad Al-Aly. He is a physician-scientist at Washington University in St. Louis. We talk about his new paper, the steps he took to make sure his findings were trustworthy, why GLP-1 drugs might work so well, what they’re teaching us about the brain and body, how they’re scrambling our sense of where volition begins and where free will ends, and what scientists should do next with the revelation that these drugs have effects that go far beyond obesity and diabetes.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Ziyad Al-Aly

Producer: Devon Baroldi

Links:

• Al-Aly et al. on the effectiveness and risks of GLP-1 drugs [link]

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Today, tech talk with an old friend of the pod, Kevin Roose of The New York Times, who is also host of the 'Hard Fork' podcast.

This is a show about everything. And it’s going to remain a show about everything because I’m a little bit interested in everything. But one cost of that purposeful lack of narrow focus is that sometimes you fail to communicate the gravity of the important things that are happening in the world.

And at the moment, I think some of the most important stories in the world are in tech—and more specifically, in the relationship between government and technology. A relationship that is closer now than it’s been in many decades.

We begin with TikTok—the most popular source of news for Gen Z in America and the most downloaded mobile app in the world in 2024. Last year a bipartisan bill signed by Joe Biden demanded that the parent company of TikTok, which is the Chinese firm ByteDance, sell its American business or else face a ban. Well, today, TikTok is legally banned in America, and also in broad use, because Donald Trump—the man who called for banning the app in 2020—saved it in 2025 by essentially declaring that he won’t uphold the law.

We then spend most of this episode talking about the crescendo of predictions from Silicon Valley that the AI frontier is nearing a breakthrough. In the past few weeks, members of OpenAI, Anthropic, and other frontier labs have claimed that they are less than three years away from building AI agents that are, to borrow their language, better than humans at everything. I ask Kevin how widespread these predictions are, whether we should believe them, what it would mean if they’re right, why they might wrong, what’s the biggest bottleneck still standing in their way, and why it’s so hard for the news media to report responsibly on a story like this, where we’re asked to take seriously the economy-shifting potential of a technology that we can’t actually report on because it doesn’t actually exist.

And then, because I’m also completely bewildered by the bonfires of corruption that are erupting in crypto-land, we close on crypto.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Kevin Roose

Producer: Devon Baroldi

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This is the first episode of a little experiment we’re trying this year, a podcast within a podcast on history that we’re calling, simply enough, 'Plain History.' There are, I am well aware, a great number of history podcasts out there. But one thing I want to do with this show is to pay special attention to how the past worked. In this episode, for example, we're using the assassination of an American president to consider the practice of medicine in the 19th century.

Our subject today is the bestseller 'Destiny of the Republic' by the historian Candice Millard, on the incredible life and absurd and tragic death of President James Garfield.

In the summer of 1876, the United States celebrated its 100th birthday at the U.S. Centennial Exhibition in Philadelphia. Of the millions of people who walked through the grounds, one was Garfield, who attended the centennial with his wife and six children. In four years' time, he would be elected president at a shocking and chaotic Republican convention. But at the time, he was a 44-year-old congressman known in Washington for being a rags-to-riches genius.

Garfield was a perfect match for the centennial grounds, which were themselves a gaudy showcase of genius. In Machinery Hall, visitors could pay for a machine to embroider their suspenders with their initials. They could gaze at one of the world’s first internal combustion engines, a technology that would in the next 50 years remake the world by powering a million cars, tractors, and tanks. They could see the first Remington typewriter and Edison telegraph system.

In the Main Exhibition Building, a little-known teacher for the deaf caused a riot with his science experiment. In one room, the teacher held up a little metal piece to his mouth and read Hamlet’s soliloquy into a transmitter. In a separate room, the emperor of Brazil, sitting with an iron box receiver pressed against his ear, heard each word—to be or not to be—reverberating against his eardrum. The teacher’s name was Alexander Graham Bell, and the instrument in question had three months earlier received a patent as the world’s first working telephone.

A few yards away, a scientist named Joseph Lister was having much less success trying to explain his theories of antisepsis to a crowd of skeptical American doctors. He claimed that the same tiny organisms that Pasteur said turned grape juice into wine also turned our wounds into infestations. Lister encouraged doctors to sterilize wounds and to treat their surgical instruments with carbolic acid. But American doctors laughed off these suggestions. Dr. Samuel Gross, the president of the Medical Congress and the most famous surgeon in America, said, “Little if any faith is placed by any enlightened or experienced surgeon on this side of the Atlantic in the so-called carbolic acid treatment of Professor Lister.” American surgeons instead believed in “open-air treatment,” which is exactly what it sounds like.

Here are three characters of a story: James Garfield, Alexander Graham Bell, and Lister’s theory of antisepsis. They were united at the 1876 centennial. They would be reunited again in five years, under much more gruesome circumstances, brought together by a medical horror show that would end with a dead president.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Candice Millard

Producer: Devon Baroldi

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Today's episode has been a long time coming. For years, more scientists and health influencers have claimed that even moderate drinking does serious damage to one's health. As someone who likes being healthy and also loves a glass of wine (or scotch), Derek really wanted to understand this issue more deeply. This week, he published a long article in The Atlantic about his research on the health effects of moderate drinking—meaning one or two drinks a night. In today's episode, he breaks down his research process and conclusions, sharing audio from his interview with Canadian health researcher Tim Stockwell, who is one of the most prominent skeptics of the supposed benefits of moderate drinking.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Tim Stockwell

Producer: Devon Baroldi

Links

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With so many confusing narratives unfolding around a fire that is still raging out of control, I wanted to talk to somebody I knew and trusted to get stories like this right. Robinson Meyer is the founder and editor of Heatmap News and a former staff writer at The Atlantic, where he covered climate news and related disasters. We talk about why this Los Angeles fire is so unusual, how it differs from most recent forest fires in California, the role of climate change, and what Los Angeles and other places can do to protect people from the inevitability of future disasters.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Robinson Meyer

Producer: Devon Baroldi

Links:

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My new feature for The Atlantic magazine is called "The Anti-Social Century." It's a long article that revolves around a simple point: Americans are now spending more time alone than ever. This surging solitude is changing our personalities, our politics, our culture, and our relationships. On this episode, University of Chicago psychologist Nick Epley joins the show to talk about why aloneness matters. We talk about his research on relationships and solitude, on why we need people in our lives, and why sometimes we disregard or misunderstand that need, and why "social fitness" is so critical to a good life.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Nick Epley

Producer: Devon Baroldi

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Happy new year! And what better way to celebrate the freshly torn calendar page than by welcoming one of Derek's favorite writers to the show to tell us what's in store for the 2025 economy. Michael Cembalest is the chairman of market and investment strategy for JPMorgan Asset Management, and the author of the truly spectacular newsletter, 'Eye on the Market.' Today, we start with stocks and describe the truly historic—and historically unprecedented—dominance of the so-called Mag-7 tech giants. Then, we draw the connection between Big Tech’s historic run and the surge of AI spending. After a discussion on the history and future of nuclear power in America, we do a pit stop on the European economy, where we evaluate the continent’s tradeoff between safety and growth, and move on to China to disentangle that economy’s slowdown. Finally, we connect it all back to a Trump agenda that is a fascinating brew of old-fashioned Reaganite deregulation, newfangled crypto enthusiasm, mid-19th century tariff obsession, mid-20th century industrialization policy, and ... a bunch of other ingredients that I think I’ll just let Michael tell you about.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Michael Cembalest

Producer: Devon Baroldi

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Our final episode of the year is also my favorite annual tradition: conversations with scientists about the most important and, often, just plain mind-blowing breakthroughs of the previous 12 months. Today we’re talking about "organ clocks" (we'll explain) and other key biotech advances of 2024 with Eric Topol, an American cardiologist and author who is also the founder and director of the Scripps Research Translational Institute. But first, Derek attempts a 'Plain English'-y summary of the most confusing thing he's ever covered—QUANTUM COMPUTING—with a major assist from theoretical computer scientist Scott Aaronson from the University of Texas at Austin.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guests: Scott Aaronson and Eric Topol

Producer: Devon Baroldi

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Why do Americans die younger than citizens of other rich countries? The most important reason is that life in America is inexcusably dangerous. The U.S. has more fatalities from gun violence, drug overdoses, and auto accidents than just about any other similarly rich nation, and its obesity rate is about 50 percent higher than the European average. Put this all together, and the U.S. is rightly considered a “rich death trap” for its young and middle-aged citizens.

That’s the bad news. Now here’s the good news. In the past 12 months, quietly and without much media fanfare, the government reported that drug deaths declined, murders declined, traffic fatalities declined, and the standard measure of obesity declined. This inside straight of good news has never happened before in the 21st century—and perhaps decades before that.

Today’s guest is Charles Fain Lehman. He’s a fellow at the Manhattan Institute whose expertise is unpacking complex trends in the most gruesome areas, like drugs, murder, and death, in America. Today, he explains why the U.S. seems to be experiencing a sort of mysterious health wave and whether we should expect it to last.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Charles Fain Lehman

Producer: Devon Baroldi

Link: https://www.theatlantic.com/ideas/archive/2024/12/violence-obesity-overdoses-health-covid/681079/

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So, here’s a scenario: It’s Monday. And you open up whatever calendar or planner or to-do list you use to organize the essential activities of the upcoming week. There’s a large project due Thursday. And an important meeting Wednesday. Your nine-to-five is chockablock with meetings, and your kid has a school function Tuesday, and there are holiday gifts to buy before Friday, and just when you’re pretty sure your week couldn’t possibly take one more featherweight of responsibilities, the HVAC unit sputters to a stop, requiring a call to the local heating and cooling guys, which obliterates four hours of Monday.

You can tell yourself that this week is cursed. Or you can tell yourself the truth: Feeling an imbalance between the time you have and the time you want to have isn’t really a curse at all. It’s a bit more like ... the definition of being alive. To see life clearly in this way is what I’ve come to think of as Oliver Burkeman brain. Oliver is the author of the books 'Four Thousand Weeks' and 'Meditations for Mortals.'

Today, in what's become a holiday tradition of sorts, we bring back Oliver to chat about doing more by doing less, the dubious benefits of scheduling, and the freedom that comes from accepting our limitations.

If you have questions, observations, or ideas for future episodes, email us at [email protected].

Host: Derek Thompson

Guest: Oliver Burkeman

Producer: Devon Baroldi

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