Building mirror life could wipe out everything on Earth. Life as we know it is built on left-handed amino acids, encoded by RNA and DNA made from right-handed sugars. Because all organisms share a common evolutionary origin, this molecular handedness is universal. In theory, we could synthesize life using right-handed amino acids—a mirror version of biology. But such life would be incompatible with all existing ecosystems. It could outcompete and destroy everything. Worse, with future technology, someone could engineer mirror-life bioweapons—bacteria immune to all our natural defenses. George Church, the godfather of synthetic biology and co-author of the mirror life paper, came on the podcast. His answer about how we might prevent a mirror-life disaster? Well, let's say it doesn't inspire much confidence.

Found one!

It's quite possible that the median Chinese voter is more reactionary and less liberal than members of the Chinese government. Arthur Kroeber explains how the government actually spends a lot of its time tempering nationalist voices in the blogosphere rather than signal boosting militaristic calls to action. Full episode with Arthur Kroeber out now!

The Roman Empire collapsed because of the bubonic plague. 60%+ death rates in many regions. Was there any way the Roman Empire could have *avoided* collapse? Full episode with Kyle Harper (@Oklahomaharper) on the shocking role of disease and climate in human history out tomorrow!

When Dylan Patel came on the podcast last fall, he suggested China could centralize compute to leap ahead in the AI race. Arthur Kroeber doesn't think this is a possibility. The Chinese tech giants (Alibaba, Huawei, ByteDance, Xaiomi) have proved their merit through success on the market, and have earned enough leverage in the government to prevent such a centralized move from happening.

How can we understand the power of ideology? Stephen Kotkin offers up NYC Mayor Zohran Mamdani as an example: “So there's this young kid who's really adept at social media who just looks like he won the primary for a Democratic candidate for mayor in New York City. And one of the things he wants to do is freeze rents because he wants more affordable housing. So he's a complete idiot in terms of facts. The way to get more affordable housing is to build more housing. If supply massively increases and it exceeds demand, the price has to go down. It's proven again and again and again. And what rent control does or freezing of rent, it inhibits the building of new housing. Because who's going to build new housing when you can't make money off of it? Rent control is what produces the lack of affordable housing in the first place. So he sees what's the problem as the solution now. Now, is he a fool? No, he's a really bright guy. He's very well educated.”

The complexity of the Roman financial system is comparable in some ways to Europe in the 17th and 18th centuries. So why didn't this catalyze an industrial revolution? Full Episode with Kyle Harper out now!

"Maybe in the future, my AI girlfriend is on the other side of the screen or something." Mark Zuckerberg responds to Dwarkesh's fears of getting reward-hacked by AR.

Ending factory farming isn't about making everyone vegetarian. The animal welfare movement made the same mistake as early environmentalists - turning a systems problem into a personal virtue test. No major social reform succeeded by first converting millions to change their habits. They changed the defaults - subsidies, procurement, regulations. You could have more impact on animal welfare while eating a burger than a vegan who believes they are doing their part. Full episode with Lewis Bollard out now!

Colossal didn't make an exact copy of a dire wolf — they made "dire wolf 2.0", an attempt to edit the minimum number of genes to capture the phenotypes that made dire wolves distinct from gray wolves. George Church, the co-founder, explains their approach: "In a way, these are more interesting than can we make a perfect copy of something, right? It's can we make, what's the minimum things we have to do to make it completely functionally?" There are millions of genetic differences between mammoths and elephants. But there are millions of differences between two elephants of the same species. In some cases, one gene can be the difference between two species. There is no single genetic marker separating species from each other. Most genes don't matter for ecosystem function. Colossus isn't recreating extinct species — they're discovering the minimum genetic changes needed to resurrect ecological roles. So, is a cold-adapted elephant that shapes the Arctic tundra functionally a mammoth?

Why has the U.S. remained so dominant for so long? Kenneth Rogoff says it’s not just policy — it’s also a string of lucky breaks. “China made a big mistake sticking to the dollar. Europe should’ve delayed bringing Greece into the Euro. We’ve been fortunate — sometimes by our rivals’ blunders.”

During the Cold War, we had the red telephone to prevent nuclear catastrophe. But with AI, the threat is decentralized, unpredictable — more than three-dimensional. It's like asking: how do you build a red phone for the Industrial Revolution?” From the latest episode with Arthur Kroeber is a leading researcher on Chinese tech and macro, and author of "China's Economy: What Everyone Needs to Know."

Arthur Kroeber explains how a breakdown in exchanges —students, journalists, and consulates—has created an asymmetric and potentially dangerous information gap between the US and China. "At any given moment over the last 15, 20 years, there have been north of 300,000 Chinese students in the United States. We're struggling to get to 1,000 U.S. students in China." The full interview with Arthur is out now!

Lewis Bollard explains Richard Dawkins' counterintuitive theory: intelligence might actually protect us from the worst of suffering. "Less intelligent animals might feel pain and fear more acutely than more intelligent animals. And that's because they can't rationalize it. They can't tell a story around it... It is just unmitigated pain. And they don't know when it's going to end."

In some parts of the Roman Empire, up to 40% of the population was enslaved. So why weren't there more slave rebellions? Kyle Harper explains the cruel and elaborate methods of slave repression in the late Roman world. Full episode out tomorrow.

When an industry optimizes for one metric, it often breaks everything else. In factory farming, this creates compounding suffering. Lewis Bollard explains how trying to solve pig boredom opens a spiral of unintended consequences. “At each step, there is a new solution that can’t solve the fundamental underlying parts of the problem. And sometimes just makes it worse.”

European equities (IEUR) are up 20%+ in 2025, far outpacing the S&P 500’s 3.8% gain. Does a potential U.S. lead in AGI justify a centralized bet on America, or is it time to rebalance? Ken Rogoff, former chief economist of the IMF, makes the case for global investment diversification—despite decades of U.S. dominance: "Europe seems to be under pressure to remilitarize. Remilitarizing would actually be good for the euro. It would be good for technology in Europe... My instinct is that these things have some regression to mean"

"Export-led economies can’t rig the global system — they have to compete. Not just on price, but by raising their game. Japan, Korea, Taiwan, China — all did it. China backed big bets (like solar), stuck with them, and outpaced us. We gave up after Solyndra." Full episode with Arthur Kroeber out now!

Novel cures for disease and aging are often cited by AI company leaders as the primary motivation for developing AGI. But George Church thinks we can achieve these benefits by using ML to solve narrow scientific questions. He thinks AGI could be a catastrophe of our own making, and it's foolish to take that risk when we can get the benefits we want in a more controlled, direct way.

“Prion diseases, fungal diseases — we don’t have nearly the same infrastructure or biomedical research for those as we do for bacterial or viral diseases.” Kyle Harper, author of Plagues Upon the Earth, on the overlooked threats that could drive the next pandemic. Full episode out now.

Everyone thought the internet would bring freedom to China. The CCP saw something else: the holy grail of surveillance. “This has bedeviled every Chinese administration for thousands of years. Now we have a panopticon because everyone is online. And if [China] controls the online universe, then [they] see everything.” Full episode with Arthur Kroeber out now.

fixed it ❤️

"Aristotle develops a theory of natural slavery that actually some people deserve to be slaves by their very nature." Kyle Harper on how the ideologies driving American and Roman slavery differ.

We’re terrible at preparing for rare but devastating risks. It took decades for people to wear seatbelts because a 1 percent chance of fatal injury felt low. The same blind spot is why almost no one talks about genetic counseling. George Church puts it this way: “Only 3 percent of children are severely affected by genetic diseases. 97 percent odds of winning — at the horse races or at the casino, you’d take them. Yeah, 97 percent of winning, good, you know? But when a child’s future is at risk, I think that’s not the right solution.”

Casey Handmer argues that investment in natural gas is doomed, even if there were no near-term geopolitical or financial risks from an AI bubble or China invading Taiwan. The fundamental problem: gas turbines need 20 years to pay back, but solar and batteries have already won on price. You're financing infrastructure that's economically obsolete before it's even built.

Casey Handmer argues AI pricing is so elastic that Anthropic could raise subscription prices 10x to fund new gas turbines. If that’s true, why is solar still the future? “The learning rate for natural gas is nowhere near as steep as solar… there are very few manufactured products easier to make than solar panels.”

Why Mark Zuckerberg doesn't believe in a fast AI takeoff despite saying AI will be writing most code in 12-18 months.

A series of volcanic eruptions caused a cold snap, which contributed to massive population decline in Rome. "We did not know this 20 years ago when I started graduate school." Full episode with Kyle Harper out now!

Evals don't give a full picture of how useful models are. Historian Kyle Harper gives a fist hand account of how Deep Research helps him and where it falls short.

Ruthlessly optimizing efficiency created the factory farming problem. But in some cases, efficiency gains from tech can have a positive impact on animal welfare. Here Lewis Bollard describes how in-ovo sexing "went from 10 years ago just being a vague idea to today, it's already a third of the European egg industry."

"When Trump came into office, he inherited approximately 100 working-level dialogues between the US and China. He got rid of all of them. 100%. He then replaced them with one, which are the trade talks he had in his first term." Arthur Kroeber on why US-China communications are at a new low, and how the effects could be disastrous.

"Different suites of cognitive abilities are favored in different environments." Evolutionary biologist Joseph Henrich explains why "general intelligence" is nonsensical — and why the skills that matter in an AI future will look very different from today.

The shift from foraging to farming was one of the most monumental changes in human history. It was also one of the most damaging. Episode with Kyle Harper out now! @Oklahomaharper

The U.S. meat lobby spends around $45M per election cycle. Far from tech or finance money. And yet, no meaningful animal welfare bill gets through without them stopping it. Part of the answer to their success is that they are never fighting alone. Agriculture, insurance, and feed suppliers all have a stake in protecting factory farming and close ranks when it is threatened. The bigger advantage is narrative. They draw on the American archetype of the hardworking mom and pop farmers. In reality, 99% of these operations are industrial, not pastoral. It is the “children’s book rule” of politics: never mess with cops, doctors, or farmers.

What would a classicist hope to find among the Herculaneum scrolls decoded by @natfriedman's Vesuvius Challenge? For historian Kyle Harper, Greek mathematics after Euclid tops the list.

Transcript: dwarkesh.com/p/kyle-harper Youtube: piped.video/QFzgSmN8Ng8 Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/5Lh…

this is Kenneth Rogoff, the former chief economist of the IMF piped.video/watch?v=P2b4TjQa…

How does Mark Zuckerberg think AGI can be monetized? "Not everyone is going to want a software engineer But if you do, that's something you're probably going to be willing to pay hundreds of thousands of dollars for."

The largest meat producers exploit climate rhetoric as cover for avoiding reforms. One of the biggest knows from its own surveys that consumers care more about animal welfare than climate. So when asked to adopt higher-welfare breeds or give animals more room, meat producers argue this would raise the carbon footprint.

Is there any upside to budget cuts to NIH and NSF? Here's George Church's answer. In addition to being a tenured professor with a lab at Harvard, George has co-founded and advises over 100 biotech companies – it's hard to think of another person with more insight into both how private and public money funds scientific progress.

There's no good reason to build a Jurassic Park for Wooly Mammoths. Kyle Harper, author of The Last Animal (release date TBD), on why de-extinction efforts are misguided.

"Sometime in the next 12 to 18 months, we'll reach the point that most code is written by AI. And I don't mean autocomplete." Full episode with Mark Zuckerberg out now!

Transcript: dwarkesh.com/p/mark-zuckerbe… Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/7Br… YouTube: piped.video/watch?v=rYXeQbTu…

Mark Zuckerberg on why Meta decided to donate the Trump Administration: "I've been pretty public with some of my frustrations with the previous administration, how they basically did not engage with us or the business community more broadly."

thank you!

Mark Zuckerberg says AI will replace mid-level software engineers in 12-18 months, but what does he think comes next? "More people, in general, spend less time working and more time on entertainment and culture. I think that is almost certainly going to continue as this goes on." Full episode out now!

Soviets in the 70s hoped tech could save their broken system without reform. It didn't work. Now China’s trying the same — betting that AI and surveillance can replace reform. “Maybe if we invest heavily in tech, we don't have to do the hard choices of deep and fundamental structural change.” The full 13-min clip where Kotkin expands on the problem of political legitimacy is linked below.

Full Episode: piped.video/watch?v=rYXeQbTu… Transcript: dwarkesh.com/p/mark-zuckerbe… Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/7Br…

What could Rome have done to catalyze exponential productivity gains? Kyle Harper, author of The Fate of Rome, says there are 3 essential things: Full episode with @Oklahomaharper out now!

Full Episode: piped.video/watch?v=rYXeQbTu… Transcript: dwarkesh.com/p/mark-zuckerbe… Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/7Br…

Transcript: dwarkesh.com/p/kyle-harper Youtube: piped.video/QFzgSmN8Ng8 Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/5Lh…

Transcript: dwarkesh.com/p/kyle-harper Youtube: piped.video/QFzgSmN8Ng8 Apple Podcasts: podcasts.apple.com/us/podcas… Spotify: open.spotify.com/episode/5Lh…