Jacob Kimmel thinks he can find the transcription factors to reverse aging. We do a deep dive on why this might be plausible and why evolution hasn’t optimized for longevity. We also talk about why drug discovery has been getting exponentially harder, and what a new platform for biological understanding to speed up progress would look like. As a bonus, we get into the nitty gritty of gene delivery and Jacob’s controversial takes on CAR-T cells. For full disclosure, I am an angel investor in NewLimit. This did not impact my decision to interview Jacob, nor the questions I asked him.

𝐄𝐏𝐈𝐒𝐎𝐃𝐄 𝐋𝐈𝐍𝐊𝐒

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𝐒𝐏𝐎𝐍𝐒𝐎𝐑𝐒

* Hudson River Trading uses deep learning to tackle one of the world's most complex systems: global capital allocation. They have a massive in-house GPU cluster, and they’re constantly adding new racks of B200s to ensure their researchers are never constrained by compute. Explore opportunities at hudsonrivertrading.com/dwarkesh\

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𝐓𝐈𝐌𝐄𝐒𝐓𝐀𝐌𝐏𝐒

(00:00:00) – Three reasons evolution didn’t optimize for longevity

(00:12:07) – Why didn't humans evolve their own antibiotics?

(00:25:26) – De-aging cells via epigenetic reprogramming

(00:44:43) – Viral vectors and other delivery mechanisms

(01:06:22) – Synthetic transcription factors

(01:09:31) – Can virtual cells break Eroom’s Law?

(01:31:32) – Economic models for pharma

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How will we feed the 100s of GWs of extra energy demand that AI will create over the coming decade? On this episode, Casey Handmer (Caltech PhD, former NASA JPL, founder & CEO of Terraform Industries) walks me through how we can pull it off, and why he thinks a major part of this energy singularity will be powered by solar. His views are contrarian, but he came armed to defend them.

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TIMESTAMPS

(00:00:00) – Why doesn’t China win by default?

(00:08:28) – Why hyperscalers choose natural gas over solar

(00:18:01) – Solar's astonishing learning rates

(00:27:02) – How to build 50,000 acre solar-powered data centers

(00:40:24) – Environmental regulations blocking clean energy

(00:44:04) – Batteries replacing the grid

(00:49:14) – GDP is broken, AGI's true value must be measured in total energy use

(00:58:45) – Silicon wafers in space with one mind each

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A deep dive with Lewis Bollard, who leads Open Philanthropy’s strategy for Farmed Animal Welfare, on the surprising economics of the meat industry.

Why is factory farming so efficient? How can we make the lives of the 23+ billion animals living on factory farms more bearable? How far off are the moonshots (e.g., brainless chickens, cultivated meats, etc.) to end this mass suffering? And why does the meat industry have such a surprising amount of political influence?

For decades, innovation in the meat industry has actually made the conditions for animals worse. Can the next few decades of tech reverse this pattern?

Watch on YouTube; listen on Apple Podcasts or Spotify.

Donation match fundraiser

The welfare of animals on factory farms is so systemically neglected that just $1 can help avert 10 years of animal suffering.

After learning more about the outsized opportunities to help, I decided to give $250,000 as a donation match to farmkind.giving/dwarkesh. FarmKind directs your contributions to the most effective charities in this area.

Please consider contributing, even if it’s a small amount. Together, we can double each other's impact and give a total of $500,000.

Bluntly, there are some listeners who are in a position to give much more. Given how neglected this topic is, one such person could singlehandedly change the game for 10s of billions of animals. If you’re considering donating $50k or more, please reach out directly to Lewis and his team by emailing [email protected].

Timestamps

(00:00:00) – The astonishing efficiency of factory farming

(00:07:18) – It was a mistake making this about diet

(00:09:54) – Tech that’s sparing 100s of millions of animals/year

(00:16:16) – Brainless chickens and higher welfare breeds

(00:28:21) – $1 can prevent 10 years of animal suffering

(00:37:26) – Situation in China and the developing world

(00:41:41) – How the meat lobby got a lock on Congress

(00:53:23) – Business structure of the meat industry

(00:57:42) – Corporate campaigns are underrated

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After my last lecture series with Sarah Paine ended, I still had so many questions. I knew we’d only scratched the surface of Sarah’s scholarship, so I immediately invited her back for another series: she graciously agreed, and we’ll be releasing the results online over the coming weeks and months!

This first lecture is focused on the balance of power in East Asia at the turn of the 20th century. Specifically, how did Japan (population 47M) defeat China (400M) and Russia (130M) to become Asia's dominant power?

For me, the most interesting thing was that Japan's surprise attack on Port Arthur at the beginning of the Russo-Japanese War (1904) helps us understand why Japan might have thought Pearl Harbor would work.

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* Hudson River Trading is one of the world's top quantitative trading firms. Responsible for around 15% of all U.S. equities trading volume, HRT powers their trades with cutting-edge deep learning models. Their in-house AI team does fundamental ML research and then applies it to some of the most competitive markets in the world. If you’re interested in joining them, you can learn more at hudsonrivertrading.com/dwarkesh.

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Timestamps

(00:00:00) – Japan’s Meiji reforms

(00:14:44) – Trans-Siberian railway & Japan’s 3-year window for empire

(00:29:58) – The most important battle in the Russo-Japanese war

(00:48:38) – China’s implosion: imperialism, civil wars, and opium

(00:59:31) – Was Russia on track to dominate Asia?

(01:14:20) – Pearl Harbor (1941) vs surprise attack of Port Arthur (1904)

(01:34:03) – Why big countries still lose wars

(01:46:56) – Grand strategy for small countries

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The Stephen Kotkin episode. Kotkin is arguably the world’s foremost expert on Joseph Stalin and has written a massive 2-volume biography on him (with a 3rd volume in the works).

No other individual had more of a profound impact on the 20th century than Stalin. He held the power of life and death over every single person across 11 time zones, and he killed tens of millions of people, utterly consumed by an ideology aimed at building paradise on Earth.

And, he was one half of the biggest and most consequential military confrontation in history (even if Hitler didn’t prove to be his match).

Watch on YouTube; listen on Apple Podcasts or Spotify.

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* Lighthouse is THE fastest immigration solution for the technology industry. All they need is your resume or LinkedIn profile to tell you which visas you’re most eligible for, and they’ll send you this eligibility document for free, no commitment required. Get started today at https://www.lighthousehq.com/ref/Dwarkesh.

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Timestamps

(00:00:00) – Was the tsarist regime the lesser of 2 evils?

(00:23:45) – The peasants brought Lenin to power, then he enslaved them

(00:37:38) – Why did so many go along with enforced famine and the Great Terror?

(01:02:26) – Today’s leftist civil war

(01:13:01) – Doesn’t CCP deserve credit for China's growth?

(01:35:13) – Why didn't somebody just kill Stalin?

(01:52:45) – Overcoming the pathologies of communism with tech: USSR vs China

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I’ve had a lot of discussions on my podcast where we haggle out timelines to AGI. Some guests think it’s 20 years away - others 2 years.

Here’s an audio version of where my thoughts stand as of June 2025. If you want to read the original post, you can check it out here.

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George Church is the godfather of modern synthetic biology and has been involved with basically every major biotech breakthrough in the last few decades.

Professor Church thinks that these improvements (e.g., orders of magnitude decrease in sequencing & synthesis costs, precise gene editing tools like CRISPR, AlphaFold-type AIs, & the ability to conduct massively parallel multiplex experiments) have put us on the verge of some massive payoffs: de-aging, de-extinction, biobots that combine the best of human and natural engineering, and (unfortunately) weaponized mirror life.

Watch on YouTube; listen on Apple Podcasts or Spotify.

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* WorkOS Radar ensures your product is ready for AI agents. Radar is an anti-fraud solution that categorizes different types of automated traffic, blocking harmful bots while allowing helpful agents. Future-proof your roadmap today at workos.com/radar.

* Scale is building the infrastructure for smarter, safer AI. In addition to their Data Foundry, they recently released Scale Evaluation, a tool that diagnoses model limitations. Learn how Scale can help you push the frontier at scale.com/dwarkesh.

* Gemini 2.5 Pro was invaluable during our prep for this episode: it perfectly explained complex biology and helped us understand the most important papers. Gemini’s recently improved structure and style also made using it surprisingly enjoyable. Start building with it today at https://aistudio.google.com

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Timestamps

(0:00:00) – Aging solved by 2050

(0:07:37) – Finding the master switch for any trait

(0:19:50) – Weaponized mirror life

(0:30:40) – Why hasn’t sequencing/synthesis led to biotech revolution?

(0:50:26) – Impact of AGI on biology research progress

(1:00:35) – Biobots that use the best of biological and human engineering

(1:05:09) – Odds of life in universe

(1:09:57) – Is DNA the ultimate data storage?

(1:13:55) – Curing rare diseases with genetic counseling

(1:22:23) – NIH & NSF budget cuts

(1:25:26) – How one lab spawned 100 biotech companies

Get full access to Dwarkesh Podcast at www.dwarkesh.com/subscribe

Arthur Kroeber is a leading researcher on Chinese tech and macro, a founding partner at Gavekal Dragonomics, and author of "China's Economy: What Everyone Needs to Know." It's the most useful, detailed resource I've found of how China actually works.

On this episode, we discuss how China achieved high-tech manufacturing dominance, and where they'll go from here. By Arthur’s account, the Chinese government is like a giant VC fund: they decide on key priorities and then spend hundreds of billions of dollars subsidizing ruthless competition at the local level. They are willing to lose huge amounts of money for a few of their bets to pay off: at China’s scale, effectiveness matters more than efficiency.

There's also a growing bipartisan consensus that we need to combat China's rise. This doesn’t make much sense to me. China is a big, powerful country at the frontier in many fields, and its economy is intricately tied in with our own. Being instinctively adversarial is both unsustainable and risky. Arthur and I discuss how we can create a productive, mutually beneficial version of this relationship.

Watch on YouTube; listen on Apple Podcasts or Spotify.

Sponsors

* Scale is building the infrastructure for smarter, safer AI. In addition to their Data Foundry, they recently released Scale Evaluation, a tool that diagnoses model limitations. Learn how Scale can help you push the frontier at scale.com/dwarkesh.

* WorkOS Radar ensures your product’s free trials go to actual users. Radar uses 80+ signals to distinguish malicious bots from real people, eliminating costly free-tier abuse. See why companies like Cursor, Perplexity, and OpenAI use Radar by visiting workos.com/radar.

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To sponsor a future episode, visit dwarkesh.com/advertise.

Timestamps

(00:00:00) – We should reconcile with China

(00:21:21) – BYD, Tesla, & Chinese EV industry

(00:36:05) – Will China have a Japan-style financial crisis?

(00:44:39) – Local debt situation is manageable

(00:57:28) – If CCP is so competent, why isn’t China richer?

(01:05:08) – How China keeps tech under control

(01:33:45) – Does China win AI?

(01:43:34) – Communication with China key for AI safety

(02:10:08) – What foreigners get wrong about China

(02:17:32) – China-US relationship future

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Ken Rogoff is the former chief economist of the IMF, a professor of Economics at Harvard, and author of the newly released Our Dollar, Your Problem and This Time is Different.

On this episode, Ken predicts that, within the next decade, the US will have a debt-induced inflation crisis, but not a Japan-type financial crisis (the latter is much worse, and can make a country poorer for generations).

Ken also explains how China is trapped: in order to solve their current problems, they’ll keep leaning on financial repression and state-directed investment, which only makes their situation worse.

We also discuss the erosion of dollar dominance, why there will be a rebalancing toward foreign equities, how AGI will impact the deficit and interest rate, and much more!

Watch on YouTube; listen on Apple Podcasts or Spotify.

Sponsors

* WorkOS gives your product all the features that enterprise customers need, without derailing your roadmap. Skip months of engineering effort and start selling to enterprises today at workos.com.

* Scale is building the infrastructure for smarter, safer AI. In addition to their Data Foundry, they recently released Scale Evaluation, a tool that diagnoses model limitations. Learn how Scale can help you push the frontier at scale.com/dwarkesh.

* Gemini Live API lets you have natural, real-time, interactions with Gemini. You can talk to it like you were talking to another person, stream video to show it your surroundings, and share screen to give it context. Try it now by clicking the “Stream” tab on ai.dev.

To sponsor a future episode, visit dwarkesh.com/advertise.

Timestamps

(00:00:00) – China is stagnating

(00:25:46) – How the US broke Japan's economy

(00:37:06) – America's inflation crisis is coming

(01:02:20) – Will AGI solve the US deficit?

(01:07:11) – Why interest rates will go up

(01:10:55) – US equities will underperform

(01:22:24) – The erosion of dollar dominance

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I’ve had a lot of discussions on my podcast where we haggle out timelines to AGI. Some guests think it’s 20 years away - others 2 years. Here’s where my thoughts stand as of June 2025.

Get full access to Dwarkesh Podcast at www.dwarkesh.com/subscribe