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Dwarkesh Podcast / episode intelligence

Evolution designed us to die fast; we can change that — Jacob Kimmel

21 Aug 2025 23 published claims 2 attributable people

Speakers in the public record

Claim mix

belief 9evaluation 6uncertainty 3commitment 2prediction 2preference 1

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Claim ledger

The useful parts, with receipts.

23 published records

02 / commitment

I imagine if we were to Rip Van Winkle ourselves into 2100 and wake up, the way we will be delivering these nucleic acid payloads is actually by engineering cells to do it, to perform this very ornate function.

“I imagine if we were to Rip Van Winkle ourselves into 2100 and wake up, the way we will be delivering these nucleic acid payloads is actually by engineering cells to do it, to perform this very ornate function.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

07 / belief

I think that's a pretty good signal that actually there's a lot of gradient to climb here and that potentially for us, the end-state products we're developing in 2100 are more like synthetic genes that have never existed, rather than just compositions of the natural set.

“I think that's a pretty good signal that actually there's a lot of gradient to climb here and that potentially for us, the end-state products we're developing in 2100 are more like synthetic genes that have never existed, rather than just compositions of the natural set.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

10 / belief

We don't actually use RL at the moment, so I don't want to overstate the level of sophistication we've got. But I think the general problem reduces down in a similar way.

“We don't actually use RL at the moment, so I don't want to overstate the level of sophistication we've got. But I think the general problem reduces down in a similar way.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

11 / belief

AKA, maybe intelligence is easier than we think, and there's a bunch of contingent reasons evolution didn't churn as hard on this variable as it could have.

“AKA, maybe intelligence is easier than we think, and there's a bunch of contingent reasons evolution didn't churn as hard on this variable as it could have.”
Speaker
Dwarkesh Patel
Publisher
Dwarkesh Podcast

12 / belief

We also know that with very targeted edits, other groups have done this, folks like Luke Gilbert now at the Arc Institute, who I think of as one of the great unsung scientists of our time, have been able to make a targeted edit in a single locus and then show that you can actually make cells divide 400-plus times over multiple years in an incubator in the lab.

“We also know that with very targeted edits, other groups have done this, folks like Luke Gilbert now at the Arc Institute, who I think of as one of the great unsung scientists of our time, have been able to make a targeted edit in a single locus and then show that you can actually make cells divide 400-plus times over multiple years in an incubator in the lab.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

13 / uncertainty

I'm not sure how to understand this claim that we know how to engage with the right hook, we just don't know what that hook is supposed to do in the body. I don't know if that's the way you describe it.

“I'm not sure how to understand this claim that we know how to engage with the right hook, we just don't know what that hook is supposed to do in the body. I don't know if that's the way you describe it.”
Speaker
Dwarkesh Patel
Publisher
Dwarkesh Podcast

14 / prediction

This year you spend $100 million training a model, next year $1 billion, the year after that, $10 billion. But it's one general purpose model, unlike, “We made money on this drug and now we're going to use that money to invest in 10 different drugs in 10 different bespoke ways.

“This year you spend $100 million training a model, next year $1 billion, the year after that, $10 billion. But it's one general purpose model, unlike, “We made money on this drug and now we're going to use that money to invest in 10 different drugs in 10 different bespoke ways.”
Speaker
Dwarkesh Patel
Publisher
Dwarkesh Podcast

15 / evaluation

Because mutations are going to be random and they're inherently small changes at the level of sequence at a given time, evolution needs a substrate where, in order to function effectively, these small changes can give you relatively large changes in phenotype.

“Because mutations are going to be random and they're inherently small changes at the level of sequence at a given time, evolution needs a substrate where, in order to function effectively, these small changes can give you relatively large changes in phenotype.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

16 / evaluation

If you just look at the rank-ordered list of what are the most frequently expressed genes in the genome by the count of how many mRNAs are in the cell, transcription factors are near the bottom. That means you don't actually need to get that many copies of a transcription factor into a cell in order to have benefits.

“If you just look at the rank-ordered list of what are the most frequently expressed genes in the genome by the count of how many mRNAs are in the cell, transcription factors are near the bottom. That means you don't actually need to get that many copies of a transcription factor into a cell in order to have benefits.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

17 / evaluation

I would say–I don't have formal way of explaining this–if you were to write out a list of well-known targets that many, many folks would agree are the correct genes to go after and to try and inhibit or activate in order to treat a given set of diseases—and the only reason we don't have medicines is that we can't figure out a trick in order to be able to drug them—it's a fairly small list.

“I would say–I don't have formal way of explaining this–if you were to write out a list of well-known targets that many, many folks would agree are the correct genes to go after and to try and inhibit or activate in order to treat a given set of diseases—and the only reason we don't have medicines is that we can't figure out a trick in order to be able to drug them—it's a fairly small list.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

18 / evaluation

We're still differentiated because we do everything in human cells with the right number of chromosomes, whereas it's very common to do things in cancer cell lines which have 200 chromosomes.

“We're still differentiated because we do everything in human cells with the right number of chromosomes, whereas it's very common to do things in cancer cell lines which have 200 chromosomes.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

19 / evaluation

If you take a selfish gene view of the world—that really this is the genome optimizing for the genome's propagation, it's not trying to optimize for any one individual—then actually optimizing for longevity is a pretty tricky problem because you have this nasty regularization term.

“If you take a selfish gene view of the world—that really this is the genome optimizing for the genome's propagation, it's not trying to optimize for any one individual—then actually optimizing for longevity is a pretty tricky problem because you have this nasty regularization term.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

20 / commitment

For instance, I have dedicated my career now to working on epigenetics and trying to change which genes cells use because I think that explains a lot of it.

“For instance, I have dedicated my career now to working on epigenetics and trying to change which genes cells use because I think that explains a lot of it.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

21 / evaluation

If these cells were not growing and they were not proliferating like mad, you probably would never be able to detect that you had actually found anything successful. It's only because success is easy to measure once you have it and—even being successful in very rare cases, one in a million—amplifies and you can detect it, that this was amenable to his particular approach.

“If these cells were not growing and they were not proliferating like mad, you probably would never be able to detect that you had actually found anything successful. It's only because success is easy to measure once you have it and—even being successful in very rare cases, one in a million—amplifies and you can detect it, that this was amenable to his particular approach.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

22 / prediction

Helping prevent you from ever having to access the intensive healthcare system, something like an inpatient hospital visit, if you can prevent even just a couple of those visits over a long period of someone's life with a medicine like an incretin mimetic, like a reprogramming medicine that keeps your liver, your immune system younger, on net that actually starts to drive healthcare spend down because you're shifting some of that burden from the administration system to the pharmaceutical system.

“Helping prevent you from ever having to access the intensive healthcare system, something like an inpatient hospital visit, if you can prevent even just a couple of those visits over a long period of someone's life with a medicine like an incretin mimetic, like a reprogramming medicine that keeps your liver, your immune system younger, on net that actually starts to drive healthcare spend down because you're shifting some of that burden from the administration system to the pharmaceutical system.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast

23 / preference

” We only work on a few cell types at NewLimit because those are some of the only cell types today with which we believe we can get really effective delivery of medicines.

“” We only work on a few cell types at NewLimit because those are some of the only cell types today with which we believe we can get really effective delivery of medicines.”
Speaker
Jacob Kimmel
Publisher
Dwarkesh Podcast
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