Dr. George Church on Dwarkesh Patel: Why Aging Is Curable

1. 0:00 – 7:37

   Aging solved by 2050

   1. GCGeorge Church0:00

      This seems like the sort of thing that could wipe out all competing life if we properly weaponize. The thing that's alarming to people like me is that biotechnology enables smaller and smaller efforts, harder and harder to detect. If we handle that properly, then we're probably gonna have almost perfect health. Why, why, why wouldn't we? You know, evolution might incorporate a few base pair changes in a million years. Now we can make billions of changes in an afternoon. All the materials that we use in mechanical and electrical engineering should be made better by biotechnologies. We might even finally get a room temperature superconductor that way.

   2. DPDwarkesh Patel0:43

      Today, I have the pleasure of interviewing George Church. I don't know how to introduce you. It would be... Honestly, this is not even an exaggeration. It would honestly be easier to list out the, um, the major breakthroughs in biology over the last few decades that you haven't been involved in. From the Human Genome Project to CRISPR, age reversal to de-extinction. So, um, you weren't exactly an easy prep. (laughs)

   3. GCGeorge Church1:04

      (laughs) Sorry.

   4. DPDwarkesh Patel1:05

      Uh, okay, so let's start here. By what year would it be the case that if you make it to that year, technology will keep, i- in bio, will keep progressing to such an extent that your lifespan will increase by-

   5. GCGeorge Church1:16

      Oh, wow.

   6. DPDwarkesh Patel1:16

      ... a year every year or more?

   7. GCGeorge Church1:18

      Right. Escape velocity is sometimes what it's called-

   8. DPDwarkesh Patel1:20

      Right.

   9. GCGeorge Church1:20

      ... for aging. Um, different people have estimates and all of those estimates are, including mine, are gonna be, uh, taken with a big grain of salt.

   10. DPDwarkesh Patel1:30

       Sure.

   11. GCGeorge Church1:30

       I think that looking at how, mainly looking at the exponentials-

   12. DPDwarkesh Patel1:35

       Mm-hmm.

   13. GCGeorge Church1:36

       ... in biotechnology and the progress that's been made in understanding, not just understanding the causes of aging, but seeing real examples where you can reverse subsets of the aging phenotype. You know, so, you're getting close to all of aging. Um, in other words, you're seeing e- instead of just saying, "Oh, I'm gonna fix the damage in this collagen, uh, in this tendon, in this limb," you're saying, "Oh, I'm gonna change a lot of things that, that are, that are common to age-related diseases, and I'm gonna get more than one at a time." I think looking at those two phenomena, the exponentials in biotechnologies and the, the breakthrough in general, uh, aging, um, not just observa- not just analysis, but synthesis and, and therapies, and a lot of these therapies are now making into clinical trials, I would not... wouldn't be surprised if 2050 would be a point, if we can make it to that point, uh, 25 years. Most of the people listening to this have a good chance of making it 25 years. And the thing is, it's not gonna be some s-

   14. DPDwarkesh Patel2:46

       Mm-hmm.

   15. GCGeorge Church2:46

       ... sudden point where you're gonna be, you know, so sick 25 years from now that it's, like, hit or miss. It's more likely that, that you're going to be healthier 25 years-

   16. DPDwarkesh Patel2:56

       Yeah.

   17. GCGeorge Church2:56

       ... from now than you thought you were going to be. There may be some, probably not some law of physics, but some economic or complexity issue that we don't know about that, that becomes a brick wall. I doubt it, seriously, but we'll have to see.

   18. DPDwarkesh Patel3:14

       Mm-hmm. Given the number of things you would have to solve to, uh, get... give us a lifespan of humpback whales, is there-

   19. GCGeorge Church3:20

       Bowhead, bowhead whales. Yeah.

   20. DPDwarkesh Patel3:22

       Sorry, yeah.

   21. GCGeorge Church3:22

       200 years. Yeah.

   22. DPDwarkesh Patel3:23

       Is there any hope for doing that from somatic gene therapy alone or would that have to be germline gene therapy?

   23. GCGeorge Church3:29

       Probably there's a, a lot of forces pushing it towards somatic. Um, for one, there's eight billion-

   24. DPDwarkesh Patel3:36

       Right.

   25. GCGeorge Church3:36

       ... people that have missed the, the germline opportunity.

   26. DPDwarkesh Patel3:39

       Yeah.

   27. GCGeorge Church3:39

       That is to say, doesn't apply to us, uh, the two of us and everybody listening to this. A- and, you know, you have to be very cautious when you say something's impossible. It's, it's safe to say it's impossible to do it this second, but you don't know what's gonna happen tomorrow or in the next decade or something. So I, I, I think there's a lot that could be done. In particular, since aging is a fairly cellular phenomenon, with proteins going through the blood and other factors going through the blood that... signaling and so forth, uh, you could imagine that if you replaced, let's say, every cell in the body, every nucleus in the body, left the... you know-

   28. DPDwarkesh Patel4:19

       Mm-hmm.

   29. GCGeorge Church4:20

       ... um, they would su- it would suddenly be young again, right? With- without going all the way back to the embryo and forward again. And there's various other things that are just short of that. If you, if you replace the cells, um, well, they, you know, they'll fit into that niche. They might displace the old cells. You know, that, that's within, certainly within the realm of modern synthetic biology, is to, is to... for cells to take over niches. I think the hardest part is brain, but even there, you know, there's some evidence that, that if you bring... even though the brain doesn't really use stem cells that much, you could artificially bring in stem cells and they could artificially fit into a circuit and learn the, the circuit and then displace the old ones in some way.

   30. DPDwarkesh Patel5:09

       Ship of Theseus kind of thing in the brain?
2. 7:37 – 19:50

   Finding the master switch for any trait

   1. DPDwarkesh Patel7:37

      You're one of the co-founders of Colossus, which recently announced that they de-extincted a dire wolf-

   2. GCGeorge Church7:42

      Yeah.

   3. DPDwarkesh Patel7:42

      ... and now you're working on the woolly mammoth.

   4. GCGeorge Church7:44

      Yeah.

   5. DPDwarkesh Patel7:44

      Do you really think we're gonna bring back, like, a woolly mammoth or... H- h- how... 'Cause like the difference between an elephant and a woolly mammoth might be like a million base pairs.

   6. GCGeorge Church7:51

      Yeah.

   7. DPDwarkesh Patel7:52

      So h- how do you think about what is the k- How do we think about the kind of thing we're actually bringing back?

   8. GCGeorge Church7:56

      Yeah. Well, so, so I think, uh, I think people get worked up about, you know, whether we, whether we are trying to bring back or have already or will ever bring back a new species. Um, and, and I think of it... If you think of it rather than as a natural thing that we're trying to do, but as a, as synthetic biology with goals that have potential societal... And people also get worked up as to whether this could possibly benefit society in any way. You know, can we really, um, you know, fix an environment, uh, to suit humans or fix the global carbon to suit humans? And the answer is we don't know, but it's worth a try, isn't it? Because it's, could be very cost-effective. Um, and the other thing, the other aspect of it is there's a whole discipline within synthetic biology of asking, "What's the minimum?" Right? And so people often phrase it into, "What's the maximum?" You know, like, "What, what can we do?" And I'm interested in both, but, you know, it's like, oh yes, there's, uh, millions of difference between, um, mammoths and elephants. There are millions of difference between elephant one and elephant two, within, within Asian elephants and between Asians and African. But not all of those are definitive in terms of what we would normally call them, you know, uh, you know, how we would normally classify them, h- what their functionality would be in an ecosystem, right? And so, so there's this exercise that people do, and, and, and we've done it, for example, with developmental biology. What's the minimum number of transfusion factors it takes to make a neuron from a, uh, pluripotent stem cell, right?

   9. DPDwarkesh Patel9:36

      Mm-hmm.

   10. GCGeorge Church9:37

       What's the minimum number of base pairs it takes to make something that will replicate-

   11. DPDwarkesh Patel9:41

       Mm-hmm.

   12. GCGeorge Church9:41

       ... to something that, uh, you know, was done in mycoplasma originally.

   13. DPDwarkesh Patel9:46

       Yeah.

   14. GCGeorge Church9:46

       Um, and these are, these... 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 or even functionally in a particular category, right?

   15. DPDwarkesh Patel10:01

       Mm-hmm.

   16. GCGeorge Church10:02

       How do we make it bigger? Could we learn the rules for how to make things bigger? Um, how to make things replicate faster, how to, you know, how to use new materials, et cetera. So I think with the dire wolf, we clearly didn't make an exact copy of the dire wolf, but the diff- but it helped illustrate, kind of educated people around the world, the, that what is the difference between a wolf, a gray wolf and a dire wolf, right? Because, you know, dire wolves, they're, they're big. Maybe they have particular coloration, you know, you know, the heads, head components tend to be bigger than the, than the leg components. Um, and so how many, how many genes do you need to do that? Maybe this was dire wolf, you know, 2.0, and we're gonna go for, go for 3.0 in, in, in successive approximation. And we might wanna develop the technology for making exact copy of something, because then we can... especially being able to make 100 variations on an exact copy, because then you, then there won't be any argument about whether you could make a dire wolf. It's a matter of whether... what, what should you make and what would be most beneficial for the species that you're making, for the environment it lives in, and for humans.

   17. DPDwarkesh Patel11:17

       Does this teach us something interesting about... If phenotypes which you think require... are downstream for many genes are in fact modifiable by very few changes, basically, could we do this to other species or to other things we might care about, like intelligence, where you might think like, "Oh, there's, there must be thousands of genes that are relevant," but-

   18. GCGeorge Church11:34

       Right.

   19. DPDwarkesh Patel11:34

       ... there's like, uh, 20 edits you need to make really to, uh, be, be in a totally different ballgame?

   20. GCGeorge Church11:38

       Yeah, I think it's a, it's... You're hitting on a very interesting, uh, question, and it's related to, you know, what's the minimum? So for example, y- you almost, uh, said it, which was, you know, for... Take a, a very multigenic trait-

   21. DPDwarkesh Patel11:53

       Right.

   22. GCGeorge Church11:53

       ... in humans, like height, is something that's, it's probably the most, uh, well-studied one, simply because no matter what gene you're s- no matter what medical condition you're studying, you collect information on height and weight and things like that. Anyway, they tracked it down to on the order of 10,000 genes.... of which we have 20,000 protein-

   23. DPDwarkesh Patel12:15

       Yeah.

   24. GCGeorge Church12:15

       ... coding genes and some of them are RNA coding genes, and they each have a tiny influence on, on height. Um, but if you take, uh, growth hormone, somato-, uh, tropin, uh, that you have extreme examples where you'll get extremely low, s- small stature and extremely high stature due to that one alone.

   25. DPDwarkesh Patel12:40

       Mm-hmm.

   26. GCGeorge Church12:40

       And in fact, it's used clinically as well-

   27. DPDwarkesh Patel12:43

       Mm-hmm.

   28. GCGeorge Church12:43

       ... uh, in, for seven different, uh, uh, medical, um, treatments. So, so that's a perfect example of how, how much we can minimize something, sometimes called reductionism.

   29. DPDwarkesh Patel12:56

       Yeah.

   30. GCGeorge Church12:56

       Reductionism isn't all bad. Um, sometimes it helps us bring a product into medicine, sometimes it helps us understand or build a tool chest or a, uh, uh, module that we can use-
3. 19:50 – 30:40

   Weaponized mirror life

   1. DPDwarkesh Patel19:50

      back to George. Can I ask you some questions about biodefense?

   2. GCGeorge Church19:52

      Yeah.

   3. DPDwarkesh Patel19:53

      Uh, 'cause some of the stuff you guys work on or, you know, quite responsibly choose not to work on-

   4. GCGeorge Church19:57

      Yeah.

   5. DPDwarkesh Patel19:57

      ... can keep one up at night. Mirror life-

   6. GCGeorge Church19:59

      Yes.

   7. DPDwarkesh Patel20:00

      Given the fact that it's, like, physically possible, why, why doesn't it just happen at some point? Like, some day s- it'll get cheap enough-

   8. GCGeorge Church20:07

      Yeah.

   9. DPDwarkesh Patel20:07

      ... or somebody will care about it en- enough that somebody just does it. What's the equilibrium here?

   10. GCGeorge Church20:11

       Right. You know, I was a co-author on a paper that, uh, that warned about the dangers of mirror life, uh, just like, you know, I, I wrote a paper long ago about the dangers of, of having the synthetic capabilities we have for making synthetic viruses, and, and to some extent of having new genetic codes. They, they, they have in c- a few things in common, but the thing about the, the advance that we were recognizing in our Science paper that was warning about mirror life is that we not only had to calculate what the possibility of error-prone, you know, escape or something like that. We don't want anything to escape that we made in the lab unless there's a general societal consensus it's a good thing. Um, and so far, there aren't too many examples of that. Um, but... Aren't any examples of that. Um, but mirror life, uh, if it could be weaponized, then it, it... We took it to a whole nother level of concern and the, and the concern was that if we got it to a certain point, it would be easy to weaponize it. And again, there's, there's practical considerations that may be the m- Most people who would consider weaponizing mirror life would probably be satisfied with weaponizing viruses that already exist, that are already pathogens.

   11. DPDwarkesh Patel21:31

       Yeah.

   12. GCGeorge Church21:32

       Um, and they wouldn't want to destroy themselves and their family and, and their legacy and everything like that. But all it takes is one, you know? One group, probably, or one person. But your question is, isn't it, is it inevitable? Uh, I don't know. Uh, could... Might be. It's quite possible it's already here. In other words, we, we already have mirror life in, in our, in our solar system or maybe even on our planet, um, it just hasn't been weaponized, right? And so it, it's just like what we were saying in the Science paper, is this seems like the sort of thing that could wipe out all competing life if it were properly weaponized, but there are probably a few things like that. Um, and what we really need to do is reduce the, the motivation to do that. Maybe increase our preparedness-

   13. DPDwarkesh Patel22:27

       Yeah.

   14. GCGeorge Church22:27

       ... for a variety of existential threats, some of which will be natural, some of which will be, you know, one disgruntled person who has-

   15. DPDwarkesh Patel22:36

       Yeah.

   16. GCGeorge Church22:37

       ... essentially too much power because, you know, over history of humanity, the amount of things that a single person can do has grown s- very significantly.

   17. DPDwarkesh Patel22:49

       Mm-hmm.

   18. GCGeorge Church22:49

       I mean, it used to be when you had your bare hands, there was kind of a limit to what one person could do. A large number of people could team up and get a, let's say, a mammoth-

   19. DPDwarkesh Patel22:57

       Yeah.

   20. GCGeorge Church22:57

       ... or something like that, but, you know, but today, one person with the, with the right connections, um, or, or with right access to technology, you know, could, could blow up a city, right?

   21. DPDwarkesh Patel23:09

       Right.

   22. GCGeorge Church23:09

       And that's a huge im- in- increase in capability, and I think we may want, wanna start dialing that back a little bit somehow.

   23. DPDwarkesh Patel23:18

       And then what does that look like in terms of not just mirror life but synthetic biology in general? Y- uh, you know, maybe we're at an elevated period of, uh, the ratio to offense and defense, but how do we get to an end state where even if there's lots of people running around with bad motivations, that somehow there's defenses built up that we would still survive, that we're robust against that kind of thing? Or is, is such an equilibrium possible, or will offense always be privileged in, in this, in this game?

   24. GCGeorge Church23:50

       Often, offense awfully does have an advantage, but so far, we haven't... You know, we, we made it through, um, the Cold War without blowing up-

   25. DPDwarkesh Patel24:01

       Yeah.

   26. GCGeorge Church24:01

       ... any, any, any hydrogen bombs, as far as I know, uh, accidentally on or in- intentionally on enemies. Um, uh, we did do, did two atomic bombs, uh, but, uh, a lot of that is based on the difficulty of building-

   27. DPDwarkesh Patel24:21

       Yeah.

   28. GCGeorge Church24:21

       ... hydrogen or atomic bombs. The thing that's alarming to people like me, uh, is that biotechnology-... enables smaller and smaller efforts-

   29. DPDwarkesh Patel24:33

       Yeah.

   30. GCGeorge Church24:33

       ... harder and harder to detect, harder and more and more subtle to the stochastic variation between people.
4. 30:40 – 50:26

   Why hasn’t sequencing/synthesis led to biotech revolution?

   1. GCGeorge Church30:40

   2. DPDwarkesh Patel30:40

      Over the last couple of decades, we've had a million-fold decrease in the cost of sequencing DNA, th- thousand-fold in synthesis. We have gene editing tools like CRISPR, massive, uh, parallel experiments through multiplex techniques that have come about. And of, of course, much of this work has been, um, led by your lab. Despite all of this, why is it the case that we don't have some huge industrial revolution, some huge burst of new drugs or some, uh, cures for Alzheimer's and cancer that have already come about? When you look at other trends in other fields, right, like, we have Moore's law, and here's my iPhone. Uh, why don't we have something like that in biology yet?

   3. GCGeorge Church31:17

      Yes, so we have something that's about the same speed, a little bit faster than Moore's law in biology. It's more recent, is one aspect of it. So we had... But we had, we could kind of stand on the shoulders of the electronics giants to, to go a little bit faster to catch up. Um, I would say we do. I mean, we have the biotech industry, which, uh, has used that, uh, exponential curve to, to get better. It's also possible we're close to the big payoff, uh, is the other aspect-

   4. DPDwarkesh Patel31:52

      Mm-hmm.

   5. GCGeorge Church31:52

      ... or the beginning of the big payoff. Um, you know, right now, we have miraculous things like, um, cures for rare diseases. We have vaccines. Uh, we have, you know, a trillion dollars probably of, of various biotech-related things if you go far enough apart. Uh, but we're kind of on the verge of really, um, combining electronics and biology more thoroughly and AI and biotech. Uh, and, and I think that's, uh... Uh, it seems like we're on the same track as, as Moore's law, if not better.

   6. DPDwarkesh Patel32:31

      Mm-hmm. What, what, what exactly are we on the verge of? What, what does 2040 look like?

   7. GCGeorge Church32:35

      Well, 2040, we're talking about only 15 years, uh, which is, you know, like one and a ha- you know, maybe two cycles of FDA approval.

   8. DPDwarkesh Patel32:46

      (laughs)

   9. GCGeorge Church32:47

      Um...

   10. DPDwarkesh Patel32:48

       2040 is post-AGI. (laughs) It's a long time.

   11. GCGeorge Church32:50

       Well, I hope it's not-

   12. DPDwarkesh Patel32:51

       (laughs)

   13. GCGeorge Church32:51

       ... post-AGI. I, I, I've, I think we're r- rushing a little bit to get to AGI, and there's lots of cool things we can do with just-

   14. DPDwarkesh Patel32:58

       Mm-hmm.

   15. GCGeorge Church32:59

       ... super AI. Um, but we need to be very cautious. I think that, that AGI... Well, anyway, we could, we could get into that.

   16. DPDwarkesh Patel33:07

       I have a question for you there, yeah.

   17. GCGeorge Church33:08

       But, but, uh, you know, I, I think that we were, we are shortening the, the, the time of getting medical products approved, uh, in a, in, still in a safe way. Uh, so I think, but that's not gonna completely change the, the exponential. It will, you know, might re- reduce it from 10 years down to... One year is our record so far for, say, uh, COVID vaccines, so maybe that'll be 10 times shorter. Maybe that, that will multiply out a little bit. Uh, I, but I think the big thing is that all our, our designs will become better, so there'll be fewer, fewer failures. The cost per, per drug will, will, will drop. There'll be things that we didn't classically consider drugs or instruments, um, kind of cer- some sort of hybrid thing. But again, I don't think that'll be completely shocking, but, but it just, it's just gonna be so much of it, you know? It's just, it's gonna be lots of diversity of, of solutions.

   18. DPDwarkesh Patel34:08

       How much more are we talking? Is it, y- are we gonna have 10X the amount of drugs, 100X?

   19. GCGeorge Church34:12

       I'm not even sure it's gonna make sense, but bet- yeah, 100X would not be completely surprising. Um, combinations of drugs will be important when you're using them intelligently. There'll be a lot, lot more, um... Some, some drugs will affect everything. So for example, you have age-related drug that could-

   20. DPDwarkesh Patel34:30

       Right.

   21. GCGeorge Church34:30

       ... that could impact every disease and it could... Um, I'm not sure the number is gonna matter so much as the, the quality and the impact and inter- intersection and, and, and, uh, and software that helps, uh, physicians and, and other, and regular citizens make decisions, yeah.

   22. DPDwarkesh Patel34:47

       Mm-hmm. A- and what specifically is changing that's enabling this? Is it just existing cost curves continuing, or is it some new technique or tool that will come about?

   23. GCGeorge Church34:55

       Well, the, the, the cost curves are affected by new tools. I mean, it's- it's not just some automatic thing.

   24. DPDwarkesh Patel35:00

       Mm-hmm.

   25. GCGeorge Church35:00

       Uh, there was a, a big dos- discontinuity between, um, Sanger sequencing and nanopores and fluorescent next-gen sequencing. That was... And so, you know, I think, uh, sometimes it's a merger of two things. So clearly, AI merging with protein design caused a step function. These step functions get smoothed out into a kind of a smooth exponential, but there, there, there are lots of them. Uh, next, the next set will probably be, yeah, a merger of AI with other aspects of biology, like developmental biology, um, merger of developmental biology with, with, um, you know, manufacturing and, uh, you know, conquering developmental biology. In other words, actually knowing how to make any arbitrary shape given, um, you know, DNA as the, as the-

   26. DPDwarkesh Patel35:54

       Mm-hmm.

   27. GCGeorge Church35:54

       ... programming material. Uh, I think that would be a big thing, uh, having just more materials in general. All the materials we use in mechanical and electrical engineering should be, uh, made better by, uh, biotechnologies.

   28. DPDwarkesh Patel36:11

       Wh- why, why is that?

   29. GCGeorge Church36:12

       Uh, why is that? Well, it's, uh, that electronics is... You know, Moore's law, I wouldn't say is stopping, but it's, it's kind of the, the, what we would call the one nanometer-

   30. DPDwarkesh Patel36:26

       Yeah.
5. 50:26 – 1:00:35

   Impact of AGI on biology research progress

   1. DPDwarkesh Patel50:26

      are you more excited about AI which thinks in protein space or the capsid space or, like, just, you know, it's like predicting some biological or DNA sequences, um, or are you more optimistic about just LMs trained on language wh- which can, like, write in English and tell you, "Here's the experiment you should run" in English? Which of those two approaches, or is there some combination that when you think about-

   2. GCGeorge Church50:50

      I, uh-

   3. DPDwarkesh Patel50:50

      ... AI and bio is more promising?

   4. GCGeorge Church50:52

      I- I'm much more excited about, uh, scientific AI than I am about language AI.

   5. DPDwarkesh Patel50:59

      Mm-hmm.

   6. GCGeorge Church50:59

      I think languages were in pretty good shape already, and what worries me is that to get to the next level of language, um, requires AGI or ASI.

   7. DPDwarkesh Patel51:13

      Yeah.

   8. GCGeorge Church51:13

      So A- a- and, you know, artificial super intelligence.

   9. DPDwarkesh Patel51:16

      Right.

   10. GCGeorge Church51:16

       And that's very dangerous. I don't think we have quite figured out how to... and there's a lot of safety organizations and a lot of safety rules and so forth. And I think what typically happens when there's an intense competition is those safety rules get-

   11. DPDwarkesh Patel51:30

       Yeah.

   12. GCGeorge Church51:30

       ... undermined and pushed aside. But even if they weren't, I do- just don't think we, I don't think we understand our own ethics well enough to educate-

   13. DPDwarkesh Patel51:39

       Yeah.

   14. GCGeorge Church51:39

       ... a completely foreign, uh, type of intelligence. I mean, we barely know how to pass it on to the next generation of humans. Um, so I think we need time to sort that out. And there's no rush. This is a completely artificial emergency. This is not like COVID-19 where we actually, millions of people were dying if we delayed of the science. This is something where if- if there ever is a crisis, it's 'cause we created it. It's not because we're trying to solve it.

   15. DPDwarkesh Patel52:07

       Yeah.

   16. GCGeorge Church52:08

       Right? And so I think we need to go very slowly on AGI and ASI and- and double down on slightly narrower scientific, uh, goals. Um, that's... and- and even now we need to be very cautious about, we need to have kind of an international consensus on what constitutes safe AI.

   17. DPDwarkesh Patel52:30

       I- I suppose we d- did build safe super intelligence. Um, how much would that, uh, speed up bio progress? Is it just, like, there's a- there's a million George Churches on data, in data centers-

   18. GCGeorge Church52:41

       Yeah.

   19. DPDwarkesh Patel52:41

       ... just, like, thinking all the time. Is it- is it a 10X speed up?

   20. GCGeorge Church52:43

       I think it would, I think it would slow it down.

   21. DPDwarkesh Patel52:45

       (laughs)

   22. GCGeorge Church52:45

       I think, I think it would eliminate it because, like-

   23. DPDwarkesh Patel52:47

       (laughs)

   24. GCGeorge Church52:48

       ... it w- the first thing it would conclude is biology is not in- not relevant to me 'cause I'm not made out of biology.

   25. DPDwarkesh Patel52:52

       Ar- I mean, suppose you get the, get- get them to care about it. They're just, like, copies of you.

   26. GCGeorge Church52:56

       Well, I don't know. That sounds a little bit

   27. NANarrator52:56

       (laughs)

   28. DPDwarkesh Patel52:56

       There's a million copies of you in a data center. What- what- how- like, how much faster is the bio progress?

   29. GCGeorge Church52:59

       (sighs)

   30. DPDwarkesh Patel53:00

       But they can't, like, run experiments directly. They're just in data centers. They can- they can just say stuff and think stuff.
6. 1:00:35 – 1:05:09

   Biobots that use the best of biological and human engineering

   1. DPDwarkesh Patel1:00:35

      Going back to the engineering stuff, often people will argue that, look, you, you have this existence proof that E, E. coli can multiply every, or d- duplicate every 30 minutes. Insects can duplicate really fast as well. Um, but then with our ability to manufacture stuff with human engineering, you know, we can do things that no an- um, nothing in biology can do, like radio communication or-

   2. GCGeorge Church1:00:57

      Right.

   3. DPDwarkesh Patel1:00:57

      ... uh, fission power or jet engines, right? So, um, like how plausible to you is the idea that we could have biobots, which are, you know, like can duplicate at the speed of insects and there could be trillions of them running around-

   4. GCGeorge Church1:01:09

      Yeah.

   5. DPDwarkesh Patel1:01:09

      ... but they, they also can have access to jet engines and radio communication and so forth? I- i- are those two things compatible?

   6. GCGeorge Church1:01:16

      Well, I mean, uh, certain things seem incompatible, uh, like the temperatures of a fission reactor-... isn't obviously compatible. But, but in, uh, but the, the possibility that once we, uh, that, that a biological system can make other things, you know, for example, it, it can, uh, you know, it can make a nest. A bird can make a nest, okay? And you consider the whole nest as part of the, the replication cycle of the bird. Um, so you can say biological thing that replicates at 30-minute doubling time could make a nuclear reactor, as that would be its nest.

   7. DPDwarkesh Patel1:01:56

      Mm-hmm.

   8. GCGeorge Church1:01:56

      Um, but you need to e- you know, expand its range of, of materials. Uh, we... in a, in a certain sense, we do this already. Humans are (laughs) a biological thing that replicates not in 30 minutes, but in, you know, 20 years or, or less. Um, and is that fundamentally limiting us? You know, probably is, uh, but, but yeah, it's, it's amazing to think about. What if you could take, you know, a cornfield or a nuclear reactor and suddenly, 30 minutes later, you got two of them, right? And then four of them and eight of them.

   9. DPDwarkesh Patel1:02:32

      Right.

   10. GCGeorge Church1:02:32

       Yeah. I mean, that's, that's quite an interesting, um, concept. But, uh, I mean, I, I think what we should start with... I teach a course called How to Grow Almost Anything.

   11. DPDwarkesh Patel1:02:42

       Mm.

   12. GCGeorge Church1:02:42

       That's, that, uh... and I work with Neil Gershenfeld who... at MIT, who had a... has a course called How to Make Almost Anything. And we're trying to meet in the middle where we can in, you know, his, um, uh, you know, mechanical, electrical engineering will meet with our biological. And in fact, neither of us can make or, or grow almost everything because there's all kinds of little gaps and things that are very hard to make in a, in a small lab, because there are things all over the world that depend on, you know, multibillion-dollar fabs to, to make things. Um, but yeah, we're eating away at it. I think that we might eventually be... you know, maybe a smaller baby step than making a nuclear reactor is making a, a phone. You, you know, you said radio communication.

   13. DPDwarkesh Patel1:03:27

       Right.

   14. GCGeorge Church1:03:28

       We should make a bio-lab. It should be a small challenge goal for the synthetic biology community, maybe iGEM or something, make, uh, you know, bacteria, make, uh, a radio. Now, actually, Joe Davis is a, is a, uh, uh, uh, artist that's been affiliated with my lab, and before that, Alex Rich's lab, and, uh, and he did make a bacterial radio, but it was kind of more on the art end than on the science end. But, uh, I think that would be a good, um, good goal.

   15. DPDwarkesh Patel1:03:58

       What would it take to do wh- whole genome engineering to such a level that for even a phenotype which doesn't exist in the existing pool of human variation, you could manifest it because your understanding is so high that you can... like for example, if I wanted wings. (laughs)

   16. GCGeorge Church1:04:17

       Yeah. Right.

   17. DPDwarkesh Patel1:04:17

       Is the bottleneck our understanding? Is, is the bottleneck our ability to make that many changes to my, to my genome?

   18. GCGeorge Church1:04:24

       So part of this has to do with just learning the rules of developmental biology, like I said.

   19. DPDwarkesh Patel1:04:28

       Mm-hmm.

   20. GCGeorge Church1:04:28

       We can determine morphology at sort of the molecular level now.

   21. DPDwarkesh Patel1:04:32

       Yeah.

   22. GCGeorge Church1:04:32

       Proteins and nucleic acids. Determining a develop-... at the cellular, multicellular level, there's a lot more things you can do a l- and a lot faster, um, but we don't know the language yet. So we gotta... that, um... I think we're on the cusp of getting the tools to do that, like the transcription factor-

   23. DPDwarkesh Patel1:04:50

       Mm-hmm.

   24. GCGeorge Church1:04:50

       ... I was talking about earlier, you know, harnessing, uh, migration, dif-... you know, um, gradients of, of factor... you know, diffusion factors, um, uh, you know, chemotaxis and so forth.

   25. DPDwarkesh Patel1:05:04

       Mm-hmm.

   26. GCGeorge Church1:05:04

       So I, I th-... that's one thing we need, but w- there's, there's a bunch of things we

7. 1:05:09 – 1:09:57

   Odds of life in universe

   1. GCGeorge Church1:05:09

      need, really.

   2. DPDwarkesh Patel1:05:10

      What discovery in biology, so n- not in astronomy or some other field, in biology, would, um, make you convinced that life on Earth is the only life in the galaxy? And c- conversely, what, what might convince you that, no, it must have arisen independently thousands of times in this galaxy?

   3. GCGeorge Church1:05:28

      Oh, I see what you're getting at. Right. I mean, so astronomy might be we, we would detect-

   4. DPDwarkesh Patel1:05:33

      That's right.

   5. GCGeorge Church1:05:33

      ... uh, you know, radio signals-

   6. DPDwarkesh Patel1:05:36

      Yeah.

   7. GCGeorge Church1:05:37

      ... or light signals that-

   8. DPDwarkesh Patel1:05:38

      Right.

   9. GCGeorge Church1:05:38

      ... um, but biology, what you would... the, the, the kind of evidence would be that you show in a laboratory using prebiotic, uh, conditions-

   10. DPDwarkesh Patel1:05:50

       Yeah.

   11. GCGeorge Church1:05:50

       ... a really simple way to get life.

   12. DPDwarkesh Patel1:05:52

       Yeah.

   13. GCGeorge Church1:05:53

       Right? Or, I mean, it's a harder proof to prove that given... because we don't know what-

   14. DPDwarkesh Patel1:05:59

       Right.

   15. GCGeorge Church1:05:59

       ... all the possible prebiotic, biotic conditions. Um, uh, and probably the number of it was vast.

   16. DPDwarkesh Patel1:06:07

       Yeah.

   17. GCGeorge Church1:06:07

       I mean, you have 10 to the 20th liters of water and, you know, at, at various different salinities-

   18. DPDwarkesh Patel1:06:14

       Right.

   19. GCGeorge Church1:06:14

       ... and drying up on the ocean and the sun and the lightning and all this stuff. But yes, if you... I think if you showed kind of reconstructed in the lab a very simple pathway from inorganics-

   20. DPDwarkesh Patel1:06:26

       Mm-hmm.

   21. GCGeorge Church1:06:27

       ... cyanide derivatives and reduced, uh, compounds all the way up to, you know, some cellular replicating structure, I think that might, um, that might lead us to believe that at least life exists.

   22. DPDwarkesh Patel1:06:44

       Yeah.

   23. GCGeorge Church1:06:44

       Now, that- there are other parts of the Drake equation that might kick in-

   24. DPDwarkesh Patel1:06:48

       Right.

   25. GCGeorge Church1:06:48

       ... which is maybe it's hard to get intelligent life-

   26. DPDwarkesh Patel1:06:50

       Right.

   27. GCGeorge Church1:06:51

       ... because intelligence isn't necessarily in your best interest. And if you get intelligent life, it's hard to maintain that without societal collapse or without robotics taking over and then killing themselves. Right? And that's hard to do experiments. But I think, to your question, I think an experiment that showed, you know, maybe multiple different ways of getting to a living system from, from nonliving systems spontaneously would be interesting. Uh, again, I'm not sure it would... it'd be very hard to prove the negative.

   28. DPDwarkesh Patel1:07:22

       Mm-hmm. Eh, eh, so I'm curious, between intelligent life and some sort of primordial RNA thing-

   29. GCGeorge Church1:07:28

       Yeah.

   30. DPDwarkesh Patel1:07:30

       What is the step at which, if there is any, where you say there's a less than 50% chance something like at this level exists elsewhere in the Milky Way?
8. 1:09:57 – 1:13:55

   Is DNA the ultimate data storage?

   1. GCGeorge Church1:09:57

      it.

   2. DPDwarkesh Patel1:09:57

      Mm.

   3. GCGeorge Church1:09:57

      Uh...

   4. DPDwarkesh Patel1:09:58

      If in a thousand years we're still using DNA and RNA and proteins for top-end manufacturing, the- the frontiers of engineering, how surprised would you be? Would- would you think, like, "Oh, that makes sense. Evolution designed these systems for billions of years?" Or would you think, like, "Oh, it's surprising that these ended up being the systems, the- whatever evolution found just happened to be the best way to manufacture or-"

   5. GCGeorge Church1:10:18

      Yeah.

   6. DPDwarkesh Patel1:10:18

      "... to store information or..."

   7. GCGeorge Church1:10:20

      Yeah. I don't think I'd be surprised either way.

   8. DPDwarkesh Patel1:10:23

      Mm-hmm.

   9. GCGeorge Church1:10:23

      Um, I can imagine it going either way. I- I can imagine making truly amazing materials using proteins as the catalysts, or maybe in some cases as a scaffold as well as catalysts. Uh, I think one- one thing that's probably already happening, so we don't have to go a thousand years out, is the number of amino acids is going up. It's going up radically from 20. I think pretty soon we'll have a system where we can have 33 and 34 new non-standard amino acids being used simultaneously with all the standard ones in a E. coli cell.

   10. DPDwarkesh Patel1:10:57

       Mm.

   11. GCGeorge Church1:10:57

       So 34 plus 20 is a lot bigger than 20. I don't think we necessarily need more- m- more than four nucleic acid components.

   12. DPDwarkesh Patel1:11:10

       Mm-hmm.

   13. GCGeorge Church1:11:10

       Uh, I mean, you... Certainly there are plenty of modified ones. There, there's a- a bunch of- of, uh, alternative base pairs, some of which don't even involve hydrogen bonds. So we could- we could have more. But I think the main thing is this information storage and whether it's bits, you know, it's, you know, digital, uh, binary is just zeros and ones. That works pretty well for-

   14. DPDwarkesh Patel1:11:33

       Right.

   15. GCGeorge Church1:11:34

       ... 99% of- of what we do electronically. So having four is better than two maybe.

   16. DPDwarkesh Patel1:11:39

       Right.

   17. GCGeorge Church1:11:40

       But do we really need six? You know, I don't know. So- so yeah, I wouldn't be surprised if we had... Uh, another possibility is that we change the backbone of DNA. So maybe keep the ACGT, but, uh, make it out of peptides now.

   18. DPDwarkesh Patel1:11:55

       Mm.

   19. GCGeorge Church1:11:56

       Um, a little bit smaller, uh, a little bit more compatible. I don't know. Um, or- or maybe that'll just be a- just a slight, you know, it could be part of the new amino acid collection.

   20. DPDwarkesh Patel1:12:10

       Mm-hmm.

   21. GCGeorge Church1:12:11

       Um, and- and there'll be more. I mean, th- these are just things that- that my primitive 21st century brain is coming up with. A thousand years from now, it'll- it'll be a whole new millennium.

   22. DPDwarkesh Patel1:12:21

       So i- it makes sense why evolution wouldn't have discovered, like, radio technology, right? But things like m- m- uh, more than, um, 20 amino acids or these different bases so that you can have store more than two bits per base pair, or, for example, the cod- uh, codon remapping scheme-

   23. GCGeorge Church1:12:38

       Mm-hmm.

   24. DPDwarkesh Patel1:12:38

       ... this redundancy, which it seems like based on your work, you can... there- there was this extra information you could have used for other things.

   25. GCGeorge Church1:12:45

       Yeah.

   26. DPDwarkesh Patel1:12:45

       So is there some explanation for why four billion years of evolution didn't already give living organisms these capabilities?

   27. GCGeorge Church1:12:53

       I think that, uh, evolution has a tendency to go with what works and the investment in making a whole new base pair, um, would have been high. Um, and- and we haven't even articulated what- what that, uh, what the return on investment would be, um, what do you get from that. We- we have made systems, uh, f- like Floyd-Royersberg and others, that where you have rep- replication and transcription and translation with this, with a sec- with a new base pair, but it hasn't been clearly articulated what that gets you, um, uh, even in technological society. So in technology, you can- you can jump to things that... where all the intermediates aren't-... you know, incrementally useful. With evolution is, as far as we know, generally limited to you have to justify-

   28. DPDwarkesh Patel1:13:45

       Mm-hmm.

   29. GCGeorge Church1:13:46

       ... uh, every change uh, uh, a- it's like some bureaucracies is-

   30. DPDwarkesh Patel1:13:49

       (laughs)
9. 1:13:55 – 1:22:23

   Curing rare diseases with genetic counseling

   1. GCGeorge Church1:13:55

   2. DPDwarkesh Patel1:13:55

      Mm. What is one, um... So we- we've talked about many th- many different technologies you worked on or are working on right now-

   3. GCGeorge Church1:14:02

      Mm-hmm.

   4. DPDwarkesh Patel1:14:02

      ... um, uh, from gene editing to de-extinction, to age reversal. What is, um, what is an under-hyped, uh, technology in your research portfolio which you think more people should be talking about but g- gets glossed over?

   5. GCGeorge Church1:14:16

      It's, it's hard to say because soon as you say it, it becomes hyped. (laughs)

   6. DPDwarkesh Patel1:14:21

      (laughs)

   7. GCGeorge Church1:14:21

      And so, if I've ever been asked this question before, it's too late. But, um, you know, I would say one thing I think is very ripe and it's very well understood in a certain sense, but is nevertheless ignored, it's kind of like the, the, the previous example I would have chosen was when making genes out of arrays. Arrays are typically used for analytic, you know, um, quantitating RNAs or something like that, so the original Affymetrix type of arrays. Um, but we turned them into gene arrays. And, and just people weren't using it. Uh, it was in nature. It was, uh, it was hidden in plain sight. Um, but anyway, it was, it was somehow under-hyped. Uh, what I would say is genetic counseling is under-hyped. It is, um, clearly competitive with gene therapy in a certain sense. I mean, clearly not for people that are already born but for people in the, in the future, not, not even distant future, in the next couple of years, um, we've got a chance of diagnosing them or diagnosing the potential parents and, and dodging, uh... And it's, and this has been in practice since 1985 in Doria-Sharim.

   8. DPDwarkesh Patel1:15:36

      Mm.

   9. GCGeorge Church1:15:37

      Perfectly reasonable community response to it, um, eliminated or greatly reduced all sorts of very, very serious inherited diseases. Um, it's sometimes dis- you know, depending on how it's presented, it's dismissed as eugenics. I think it's rarely th- have I heard Doria-Sharim described that way, and rightly so. What they're doing is standard medicine, you know. Whether you, you know, cure these kids as soon as they are newborns or whether you, uh, counsel the parents so the same disease is, is missing, um... The, the, the problem with eugenics was that it was forced, the government forced it on people. It wasn't that it enabled people to make a choice.

   10. DPDwarkesh Patel1:16:23

       Right.

   11. GCGeorge Church1:16:23

       It's that it removed the choice-

   12. DPDwarkesh Patel1:16:25

       Right.

   13. GCGeorge Church1:16:25

       ... from the people. That was what was wrong. And that's the confusion someone said... But I don't think that's the explanation for why this is under-hyped. I think it's people when they're dating, they're not thinking about reproduction necessarily. And when they're thinking about reproduction, they're not, you know, they're, they're not necessarily thinking about serious genetic diseases because they're rare. I think it's our, uh, difficulty with dealing with rare things.

   14. DPDwarkesh Patel1:16:51

       Mm.

   15. GCGeorge Church1:16:51

       It's like there was great resistance to seat belts, um, because less than 1% of people died in automobile accidents or even got hurt. Um, great resistance to stopping smoking. Really, uh, it's hard even for us to imagine how great the resistance was for seat belts and smoking. Um, and, but eventually, we got, we got over it. I think this is a similar thing, which is that only 3% of children are severely affected by genetic diseases. And they feel like, "Well, I'm not that unlu- you know, I'm, I'm, I'm in the 97%" Right? You know, 97% if those were your odds of winning, you know-

   16. DPDwarkesh Patel1:17:30

       Right.

   17. GCGeorge Church1:17:30

       ... at the horse races or at, or at the casino, you'd take 'em. Yeah, 90%, 70% of winning, good, you know. But with, with, you, you know, when a children's, uh, when a child's future is at risk, I think that's, uh, it's not the right-

   18. DPDwarkesh Patel1:17:44

       Yeah.

   19. GCGeorge Church1:17:45

       ... solution. And, uh, uh, the other thing is I think it's, has to do with the trolley problem. It's like, if you don't influence it, it's not your fault. But actually, everything is your fault, you know. Not doing something is a decision, right?

   20. DPDwarkesh Patel1:17:57

       Right.

   21. GCGeorge Church1:17:58

       And so I, I think it's like, "If I just don't do anything and they come out damaged, well, it's not my fault." But-

   22. DPDwarkesh Patel1:18:04

       Yeah.

   23. GCGeorge Church1:18:04

       ... it is, yeah.

   24. DPDwarkesh Patel1:18:05

       Uh, David, David Reich was talking about how in India especially because of the long running history of caste and-

   25. GCGeorge Church1:18:12

       Yeah.

   26. DPDwarkesh Patel1:18:12

       ... um, endogamous coupling that there have been these small cell populations that have high amounts of recessive diseases. And so-

   27. GCGeorge Church1:18:18

       Yeah.

   28. DPDwarkesh Patel1:18:18

       ... like, there it's especially, uh, valuable intervention.

   29. GCGeorge Church1:18:21

       I, I think that's a... Yeah, I, I know what you're saying and, and what David is saying, but I think it's a dangerous dichotomy.

   30. DPDwarkesh Patel1:18:27

       Mm-hmm.
10. 1:22:23 – 1:25:26

    NIH & NSF budget cuts

    1. DPDwarkesh Patel1:22:23

       All right. Some, uh, some final questions to close us off. If, um, 20 years from now, i- if there's some scenario in which we all look back and say, "You know what? I think on net it was a good thing that the NSF and the NIH and all these, uh, budgets were blown off and got doged and so forth." I'm not saying you think this is likely, but suppose there ends up being a positive story told in retrospect, what might it be? Would it have to... would maybe we come up with a different funding structure, basically, like, yeah, what, what is the best case scenario, uh, if this, uh, post-war system of basic research is upended?

    2. GCGeorge Church1:23:00

       Uh, foof. Um, I, I have to preface this by, by, you know, say- when scientists explore, answer a question and explore possibilities, it doesn't mean they're advocating it.

    3. DPDwarkesh Patel1:23:13

       Mm-hmm.

    4. GCGeorge Church1:23:13

       Y- I've... in the past, people have asked me off-the-wall questions about Neanderthals, for example, and then it was described as if I was enthusiastic about it. So, not enthusiastic about NIH and NSF budgets being cut. Um, you could say, well, it make, it forces us to think more seriously about philanthropy and industrial sponsored-research. That could be a positive thing. Um, it could be that that makes us listen more carefully to what society actually needs rather than doing basic research. I'm a big proponent of basic research, but also maybe I'm more than average connecting the basic research to societal needs from the get-go. It doesn't-

    5. DPDwarkesh Patel1:23:58

       Yeah.

    6. GCGeorge Church1:23:58

       I don't think it actually interferes with basic research to think and act on societal needs at the same time. So that would be... that could be a positive. It could be that it, it creates a, uh, another nation state that now is the dominant force, you know, like China could now become-

    7. DPDwarkesh Patel1:24:16

       Right.

    8. GCGeorge Church1:24:16

       ... the next empire after-

    9. DPDwarkesh Patel1:24:18

       This is a positive story? (laughs)

    10. GCGeorge Church1:24:19

        ... U- U- US, yeah. Well, it could be for China, right?

    11. DPDwarkesh Patel1:24:22

        (laughs)

    12. GCGeorge Church1:24:22

        I mean, you didn't specify who it's a positive story for. You know, the, the US would displace Britain, which would displace, you know, Spain and Portugal.

    13. DPDwarkesh Patel1:24:30

        Right.

    14. GCGeorge Church1:24:30

        You know, it, it keeps, keeps moving. Um, fresh blood is sometimes a good thing. Again, I preface this by saying-

    15. DPDwarkesh Patel1:24:37

        (laughs)

    16. GCGeorge Church1:24:37

        ... I'm not advocating this. Um, what else could go well? You know, there's just certain things that we, the society is fairly good at doing collectively that we're not good at doing individually.

    17. DPDwarkesh Patel1:24:51

        Mm-hmm.

    18. GCGeorge Church1:24:51

        You know, building roads, schools, and science are examples of that. Doesn't mean we couldn't learn how to do that, you know, it c- you know, uh, you know, to some extent when you build a gated community, a lot of that is done with private funding. It's possible we could figure out how to build roads and schools and just about everything. It, it means we're gonna run into some kind of hyper-capitalism.

    19. DPDwarkesh Patel1:25:18

        Mm-hmm.

    20. GCGeorge Church1:25:19

        That might mean, you know, there's all kinds of pathologies that come along with that, that-

11. 1:25:26 – 1:26:32

    How one lab spawned 100 biotech companies

    1. DPDwarkesh Patel1:25:26

       Wh- what is it about the nature of your work, maybe biology more generally, that makes it possible for one lab to be behind so many advancements? I don't think there's an analogous thing in computer science, um, which is a field I'm more familiar with, where you could go to one lab and, uh-

    2. GCGeorge Church1:25:44

       One academic lab, yeah.

    3. DPDwarkesh Patel1:25:45

       Yeah. Sorry, one academic lab, and then 100 different companies have been formed out of it, including the ones that are most exciting and, uh, doing a bunch of groundbreaking work. So, is it something about the nature of your...... um, academic lab? Is it something about the nature of biology research? Uh, wha- wha- what explains this pattern?

    4. GCGeorge Church1:26:03

       Well, f- first of all, thank you for being so (laughs) generous in your evaluation, which may be, um, taken with a grain of salt. But, uh, I, I think that what it is being in the right place at the right time, so, um, Boston is a unique culture. Um, it attracts some of the best and brightest students and post-docs automatically. It, it has a, it, it is a dense enough, you know ... There, there's, sometimes people wanna spread the wealth out evenly all over the universe-

Episode duration: 1:34:28