Biophysics w/ Raghuveer Parthasarathy

In this episode of Talk Nerdy, Cara is joined by University of Oregon Biophysicist Dr. Raghuveer Parthasarathy to talk about his new book, "So Simple a Beginning: How Four Physical Principles Shape Our Living World." They discuss how the principles of self-assembly, regulatory circuits, predictable randomness, and scaling underpin all of life on Earth. Follow Raghuveer: @RParthasarathy7

• READ A TRANSCRIPT OF THE SHOW, PROVIDED BY ZENCASTR!

  Descriptio00:00.00

  talknerdy

  Well Raghuveer, Thank you so much for joining me today I am looking forward to talking all about your new book. So simple a beginning. But before we dive into it I have to just say upfront I realize when looking at your bio.

  00:03.25

  Raghuveer

  Thanks! Thanks! A lot for having me.

  00:18.30

  talknerdy

  That you since you're at the University Of Oregon you actually live in Eugene which is where one of my very best friends lives and I've been seeing all this snow on her Instagram and I'm super jealous.

  00:22.94

  Raghuveer

  Um, our need is that. Ah, it is very unusual. We get typically something between like zero and two days of snow a year so when it does know it's it's quite an event and you it paralyzes the city of course as well. So it's oh yes, exactly you know.

  00:36.36

  talknerdy

  Yeah, of course yeah, it's like like the rain down here in l a which has been incessant for the past two weeks but we need it? Um, but yeah, you guys had a legit white Christmas what? Ah what a rare treat.

  00:48.16

  Raghuveer

  It is yeah and it's well it reminds me I actually spent 5 years in Chicago that's where I went to to graduate school and it reminds me that snow is really beautiful but I really really dislike being cold. so so yeah sort of conflicting thoughts in my mind about.

  01:00.46

  talknerdy

  Ah, same? Ah, but you're still pretty far North I mean Pacific Northwest It gets pretty cold I mean for somebody who doesn't like the cold you picked a spot where you're going to be dealing with it.

  01:06.90

  Raghuveer

  But all of that.

  01:10.96

  Raghuveer

  Well be well cold. My threshold is freezing Basically like if it's above freezing I'm I'm okay and I actually don't mind like sort of clouds and drizzle and stuff like that. So yeah that that's okay with me. But.

  01:18.28

  talknerdy

  I see.

  01:27.40

  Raghuveer

  Once it gets to yeah below freezing I just feel like it's just seeps into all my bones and like there's no glove That's ever been invented that keeps my fingers warm and.

  01:30.59

  talknerdy

  Ah, for real. It's so painful and of course I'm living here in l a it's like 55 out today and I'm like oh god it's too cold. You definitely adapt. It's so funny depending on where you live I mean the fact that you spent 5 years in Chicago.

  01:37.38

  Raghuveer

  Oh you say? yeah, that's true. Yeah. Oh yeah, I mean there were some days I would be just you know, walking around downtown going somewhere else and like that I just I would sit there wondering like who put a city here like what what were they thinking I grew up actually well not too far from you mostly in San Diego so yeah Southern California

  01:49.26

  talknerdy

  Talk about cold wind.

  01:57.17

  talknerdy

  So so where did you grow up.

  02:07.97

  talknerdy

  Mm.

  02:09.00

  Raghuveer

  I was born in India but my parents moved to the us when I was about a year old I lived in Minnesota a little bit but it was a small child but from like third grade through seventh sorry third grade through high school Southern California yeah

  02:18.87

  talknerdy

  Oh cool. So this might be kind of a an ignorant question but I'm curious if you moved here when you were 1 did you have to go through the full or or have you or did you decide to go through the full naturalization process.

  02:29.95

  Raghuveer

  Oh um, yeah I did become a naturalized citizen when I was I forget if it was 12 or 14 but it was just before I was just young enough that I didn't have to take the test but I did have to you know fill out the forms and and go through the ceremony which was quite nice. So I still remember that.

  02:40.60

  talknerdy

  Ah, yeah, oh cool. So there's still a ceremony for Kiddos but they don't have to do quite as much homework. That's good to know? Yeah, ah, that's good to know.

  02:49.79

  Raghuveer

  Correct Yeah, or at least that was the case you knew when I did it which was a wild gun outfit. Yeah yeah, so yeah.

  02:58.12

  talknerdy

  So you know growing up in Southern California were you always? um, like a physics nerd is this something that came to you were you like a science kid or is it something that came to you later in life.

  03:04.69

  Raghuveer

  Yeah, so that's an interesting question and and it's It's also an interesting one that even relates to to my book and the things I work on now because you know so I work on this this field of biophysics which is kind of like this intersection or or mashup between physics and biology and. Everybody comes to that from kind of different ways and for me like when I was a kid I was definitely interested in in like math and science and I was actually interested in in physics more than than anything else and so when I went to college which is.

  03:34.22

  talknerdy

  E.

  03:40.40

  Raghuveer

  You see Berkeley My my default plan. Yeah I started out intendeding to be a physics major and I did major in physics but I couldn't stand biology I was alright maybe couldn't stand as perhaps too strong but I had no interest in biology and I I didn't mesh with what I thought I liked sort of about all I was. Interested in physics I was interested in math I was interested in in Astronomy also and actually started out college. Oh yeah, oh interesting. Yeah well well like I was saying. Yeah.

  04:01.43

  talknerdy

  Ah, you were my equal and opposite I was like all bio all the time like please don't make me take another physics course.

  04:15.41

  Raghuveer

  Biophysics just where I'm at now people come at it from all kinds of different routes which is actually one of the things that makes it a fun field. But yeah I had this real love of the the kind of ability of physics to sort of predict things and say things about about the the natural world.

  04:16.29

  talknerdy

  Yeah, yeah.

  04:33.25

  Raghuveer

  And especially to do it like quantitatively and kind of exactly and and stuff like that and I also I was interested in astronomy too and I started as a double major in physics and astronomy and um I actually ended up dropping the astronomy major not because I found it uninteresting but. Actually ended up being involved in this wonderful project to build like an undergraduate project to build a radio telescope so a bunch of us put just tons of time to this and built this this working radio telescope on the roof of one of the buildings at Berkeley and.

  04:59.40

  talknerdy

  Ooh.

  05:07.64

  Raghuveer

  Pointed it up at the galaxy and you could measure how fast the the galaxy was rotating and stuff like that and it was it was It was a lot of work but it was really extremely rewarding but I became more and more fascinated by the fact that you could build this thing. That can detect these little weak little radio waves that are so weak that you know the total sum The total of all the power in them that's hitting the entire surface of the Earth is less than that of one hundred wattlight bulp but you can build something that detects that and I thought you know that's really cool.

  05:38.30

  talknerdy

  Wow.

  05:44.21

  Raghuveer

  That's actually even cooler than the Hydrogen. We're pointing the telescope at so I kind of moved more and more towards kind of the more tangible end of physics and that took me I'll skip over a lot of the intermediate steps but it took me to but. Even things that are you know, really tangible that you can sit there and you poke your arm and see how squishy you are and like what are the physical properties of like living things and so that's been a fun journey.

  06:07.30

  talknerdy

  I Love that and so you really came to the biophysics through the how does stuff work. What are the sort of subcomponents. How do we detect them but in doing so did you discover? um, an interest or a love for biology or is it still kind of like.

  06:13.77

  Raghuveer

  Yeah.

  06:21.53

  Raghuveer

  Oh very much. Yeah, no, no, no, no no I mean I now I Just absolutely adore biology. Um, and I have to say you know I think this is something that is also maybe mirrored in people with the opposite experiences of mine I Really love biology.

  06:24.92

  talknerdy

  Corner.

  06:40.34

  Raghuveer

  I'm not terribly fond of the way. It's taught often. Um, so and I think people often say the same kind of thing about physics and and yeah, think there's a lot that that can be done on on both realms. Um, but ah yeah I adore biology and I should say even throughout like even when I was in high school and things.

  06:40.99

  talknerdy

  Oh yeah, sure sure.

  06:58.92

  Raghuveer

  Wasn't fond of biology as a subject but I love being outside and sort of nature and those sorts of things and now I find biology itself just utterly fascinating but 1 of the things that I find kind of most amazing about it is that it has all these just wonderful phenomena and. Creatures and substances and activities and all of that. But it turns out that it it is actually possible to like say precise things about it and quantitative things about it and that actually helps us like understand it and even illuminate how remarkable some of these things are so you know now.

  07:23.33

  talknerdy

  E.

  07:33.57

  Raghuveer

  Is very much I think kind of a biophysical perspective. You don't sort of see these things as like opposite in how we can can tackle them. But as as very sort of complimentary or or conjoined.

  07:43.52

  talknerdy

  It is interesting. How for many people I think many scientists especially who develop a passion for a subject or for a construct they enter it through a certain discipline and very often that discipline really serves as a window to another discipline.

  07:56.96

  Raghuveer

  Is it? yeah.

  08:03.50

  talknerdy

  That maybe felt untouchable I had a very similar experience because my background was psychology and philosophy and that's how I found biology was through neuroscience. So I came at it from a like a behavior and I want to describe Behavior and oh my gosh look at all the cool things that are happening at the network level and the cellular level and then of course my um.

  08:10.52

  Raghuveer

  Um, ah I mean is it.

  08:22.91

  talknerdy

  My professor through my ah through my master's which was in neuroscience um was a biophysicist. He was a neurophysicist um and actually a physiologist and so I learned a lot of physics through that but it was all very related to nerve cell transmission and um.

  08:27.78

  Raghuveer

  And.

  08:37.95

  Raghuveer

  Yeah, listen.

  08:40.97

  talknerdy

  It was cool. It was really cool to like see a whole side of this subject that like I never got in you know intro to physics class.

  08:45.41

  Raghuveer

  Right? Yeah and it is really true that yeah, especially you know having a background in 1 thing and kind of using that as a stepping stone to another I think really gives you maybe a better appreciation for both of them.

  08:58.50

  talknerdy

  Yeah, yeah, yeah for sure and and of course you're in this field. That's so multidisciplinary like you have to really consider um it from all angles and I feel. Like to some extent.. It's very hard to stay siloed in the sciences in the modern world because almost nothing is Siloed anymore were basic science. Yeah.

  09:19.98

  Raghuveer

  That's true. Yeah I mean there there are people who do it good but ah but I don't know why? yeah.

  09:25.95

  talknerdy

  But right like like we know so much now and there's still obviously so much more to know, but we so we know so much about the natural world that you can't really speak of a phenomenon without speaking of the chemistry the physics the biology like all of the different components.

  09:43.43

  Raghuveer

  Yes, yeah.

  09:44.12

  talknerdy

  Of that phenomenon and so so okay, you you take a book that is so not simple and describe it from this sort of ah foundational point of simplicity right? So simple a beginning How 4 physical principles shape our living world. So of course even The. Cover image is this idea of this like a branching you know, increasing in complexity sort of um, ah phenomenon because we can go down to to basic principles and you do in the book you you focus on 4 specific ones that sort of are foundational. But.

  10:16.50

  Raghuveer

  Is it.

  10:23.61

  talknerdy

  So much complexity so much almost in seemingly ostensibly inscrutable but of course isscrutable complexity comes from these four basic principles. So talk to me about that like like how do you I mean really, it's like how do you even determine.

  10:32.66

  Raghuveer

  Yes, yeah, yeah, yes.

  10:43.13

  talknerdy

  What is the fundamental without getting too fundamental. You know it's like it's it's like frogs all the way down like how do you? How do you split.

  10:44.58

  Raghuveer

  Right? Well I think that this yeah well I think this this really comes to the notion of what do we mean by by principles and this is something that that I am I think kind of most happy about with the book and that really took a lot of time thinking you know what? what are the kind of themes that.

  10:52.62

  talknerdy

  M.

  11:04.17

  Raghuveer

  Make sensible that that allows to make sense of a lot of this complexity and so one of them so I can I'll illustrate what there but but 1 of them which is I think very kind of visceral and very powerful is this idea that nature not just living things but this is really you know. Predominant in in the living world makes use of this idea of self-assembly and that is just this notion that you know the instructions for how something is put together are kind of encoded in the thing themselves so to be concrete with the.

  11:25.89

  talknerdy

  E.

  11:35.63

  talknerdy

  In.

  11:41.72

  Raghuveer

  With a non-biological example this is why I actually have like an introduction that you know maybe like so simple. It seems like obvious to people but it's it's worth thinking about you blow a soap bubble and you know we've all done this. It's lots of fun. You can go home and do it in your kitchen again. But you know you blow a soap bubble and you get this nice spherical. Um, spherical shape and you can ask yourself? Well, you know why is it? Why is it a sphere and you know we all know that nobody had to sit there and like you know poke at the soap bubble and turn it into a sphere. You didn't do anything like that. It just turned itself into a sphere and that's because you know it.

  12:15.85

  talknerdy

  So no.

  12:20.90

  Raghuveer

  Is made up of a liquid and it turns out that liquids you know all the molecules in a liquid they like to be next to one another so they don't like to be at a surface so they try to just make the smallest surface that they can and the shape with the smallest surface for some amount of volume is a sphere.

  12:34.85

  talknerdy

  Right.

  12:36.66

  Raghuveer

  So we can say that that soap bubble just assembles itself into this spherical shape so that that notion is a really really general and continuing with soap bubbles. There's something else you can try at home and it's it's ah you know, but challenging to do this as a podcast because you know.

  12:54.55

  talknerdy

  Ah, yeah.

  12:55.24

  Raghuveer

  Have illustrations of this in the book put you you you can't even see me waving my and the hands of the form of illustrations. But if you if you go to your kitchen take some dish so blow some soap bubbles and and you get them to to set on a pick piece of wax paper or some like what surface or something like that and you have like 4 soap bubbles that are touching. What you'll find is that there's a very particular arrangement that they make you'll never get them. Um with their kind of borders making an X so they're all kind of coming together at like 4 corners that you'll never ever find that instead you'll get something where the junction looks kind of like ah like an h with twisted arms.

  13:25.25

  talknerdy

  E.

  13:32.76

  talknerdy

  Okay, right right.

  13:32.81

  Raghuveer

  Sorry with h with bent arms. So something where 2 were touching each other and then you have 2 kind of on the side and there again nothing had to you didn't have to make that shape. That's just what force soap pobbles will do so what some people have noticed now going to living things if you look at the cells in the flies. Retina.

  13:42.58

  talknerdy

  He.

  13:52.24

  Raghuveer

  So if I you know you have these compound eyes you have these photoreeptor cells in each of those compound units and they're these groups of 4 cells and you look at them under the microscope and what they look like is that exact same pattern that four soap bubbles make so the arrangement of cells.

  14:06.20

  talknerdy

  Oh interesting.

  14:11.75

  Raghuveer

  Looks very much like what 4 soap bubbles would make the same angles the same you know 2 things contacting each other and 2 things to the side. So what a couple of researchers did is you know they made that observation like many others have and they looked at mutant flies that instead of 4 have like 3 or 5 or 6 or or whatever of these photoreceptor cells. And it turns out make exactly the same arrangement as 3 or 5 or 6 or whatever soap bubbles make so what it tells you or at least what it strongly suggests to you is that the fly doesn't have to sit there and have a gene that positions every cell in its every photo receptor cell in each compound eye.

  14:34.70

  talknerdy

  E.

  14:49.24

  Raghuveer

  Can make these and rely on kind of physical forces. The same things that are pulling soap bubbles into particular arrangements to put the eye cells in the arrangement that they need to be in.

  14:57.46

  talknerdy

  Right? So the idea here is that it's just simply the most conserved or maybe a better way to put it the least or sorry the most efficient way for the cells to arrange themselves right.

  15:07.83

  Raghuveer

  That's a way to think about it. Yeah, the most kind of efficient or energetically favorable or the thing that physical forces would make if you just let them do their thing.

  15:15.57

  talknerdy

  Right? It just it like you don't have to put anything extra into the system to get it there. It's like the least least amount of energy required.

  15:20.15

  Raghuveer

  Exactly exactly exactly and nature does this all the time. So like the the boundaries of your cells. You have a cell membrane. So this beautiful. It's amazing. Essentially 2 moleculele thick layer of.

  15:29.69

  talknerdy

  M.

  15:37.30

  Raghuveer

  Stuff That's mostly made up with these molecules called lipids that have a ah part. That's they're much very much like soap molecules part of them likes water part of them doesn't so this is exactly yes Yes, so these membranes they're absolutely crucial if your membranes disappeared you would you know you would die in an instant you know they're They're definitely important things.

  15:43.58

  talknerdy

  Right? They're phosphol lipids right.

  15:52.40

  talknerdy

  Right.

  15:56.71

  Raghuveer

  You might ask yourself? Okay, what what protein sits there and makes makes a membrane or what Gene encodes the shape of a membrane and the answer is there is not all your cell has to do is exactly yeah the cell just makes the lipids and.

  16:03.60

  talknerdy

  Right? Because the little the lipids just stick to each other. Yeah.

  16:12.25

  Raghuveer

  Lipids if you just take a bunch of lipids and toss them into water they will form themselves into a membrane shape just because that's the shape that takes the parts that don't like water and hides them away from the water and sort of the interior part of this membrane. It takes the parts that like water and oh yeah, exactly? Yeah yeah, yeah, yeah, so.

  16:15.60

  talknerdy

  Yeah.

  16:22.52

  talknerdy

  Yeah, everybody's seen it when they make a really fatty broth. There's literally like a skin that forms on top. That's what that is yeah.

  16:32.90

  Raghuveer

  So this notion that life just really loves to make use of self-assembly that you don't have to specify you know the biochemical reaction or the the specific location of of all these things you can make the stuff and the stuff encodes its own instructions.

  16:36.74

  talknerdy

  E.

  16:50.81

  Raghuveer

  That's a theme that just makes so many things make sense.

  16:52.54

  talknerdy

  Yeah, yeah, okay so and self-assembly is something that it seems like I mean tell me if I'm wrong I've been doing sicom now for probably coming up on 15 years and covering you know all different fields and when you see um, ah.

  17:11.50

  Raghuveer

  Yes.

  17:12.70

  talknerdy

  Material science articles um dropping it seems like there's always a real push for self like self-assembly within material science like how do we get certain materials to um, do this on their own. Yeah.

  17:21.14

  Raghuveer

  Oh definitely definitely so yes and actually it's it's neat that you brought that up because that actually more directly. It was my path to biophysics. Um I actually did my Ph D work I had a little bit of sort of a biophysical side project but the bulk of what I got my Ph D in.

  17:29.43

  talknerdy

  Right? right? okay.

  17:39.75

  Raghuveer

  Like the University Of Chicago Chicago was actually something non-biological it was getting like gold nanocrystals to to making kind of electrical devices out of little gold nanoparticles and the key to it was getting them to assemble themselves so we would coat them with particular things and they would.

  17:48.62

  talknerdy

  Right.

  17:57.50

  Raghuveer

  Just from physical forces. You'd get this kind of beautiful hexagonal lattice of particles and then if you messed it up, you'd get bad lattices and stuff like that and we'd looked at you know we looked at yeah yeah, our electrical current wouldn't flow through in the same way stuff like that. So I found that like just made really fascinating.

  18:03.98

  talknerdy

  Yeah, yeah, and then they wouldn't be as strong or yeah, functional right. Oh yeah.

  18:16.26

  Raghuveer

  And once we kind of figured out what to do you know the technique was yeah we we put the right coating on. We had our nanoparticles in Liquid we put that on a chip we went out got some coffee came back and it had assembled itself into this this beautiful.

  18:28.80

  talknerdy

  Ah I love that oh that's so and of course we see this all the time with like actual crystals with different minerals and stuff the way that they just sort of quote grow. Um, even though they're not alive which is very cool and and self-organize and.

  18:34.33

  Raghuveer

  Um, oh of course? Yes, yes, yeah, yeah, yeah, right? Yeah right.

  18:45.29

  talknerdy

  I remember even you know my own experience when I was doing like I said back? Um, back in my master's like way back when um I was doing ah work in a ah cell culture laboratory and we were we were working with what we called Monolayer nerve cell networks so we would.

  18:59.37

  Raghuveer

  Is it nothing.

  19:02.82

  talknerdy

  I Would do this very complicated thing where I had to take these like ah these mice that weren't yet born and take their brains out and and remove the individual portions of the brains and separate the cells out so that they were just individual cells and you know using all these different solutions and stuff put them on these little plates and they would just.

  19:10.75

  Raghuveer

  Um, different.

  19:22.31

  Raghuveer

  Yeah.

  19:22.78

  talknerdy

  Grow into nerve cell Networks They would just grow into these flat networks on their own and of course there we do have a lot of coding involved right? There's the trophic factors and the tropic factors and all the things that are released that tell the neurites to grow in whatever direction they grow but in a way that also is a.

  19:30.18

  Raghuveer

  Everything.

  19:42.69

  Raghuveer

  Oh very much. Yes, yes, and that's something that I also touch on in the book. It's great that you brought up that specific example because you know you can think about kind of simple things like nanostructus and then actually from there in my own career I Went to.

  19:42.75

  talknerdy

  Form of self-assembly.

  20:01.26

  talknerdy

  Li.

  20:01.90

  Raghuveer

  Studying membranes in fact and this kind of you know one step up in kind of sophistication example of self-assembly that brought me to like actual living things. But then you know one of the the currently just super exciting topics in kind of Science biotechnology is building what are called like organoids.

  20:19.58

  talknerdy

  Yes, oh my gosh I Thought oh yeah I just covered a story recently about this one organoid that was built that had eye spots. Did you see that and they just naturally they just spontaneously developed like they didn't plan for that.

  20:20.80

  Raghuveer

  So getting? Yeah so I have a chapter on that. Yeah, exactly and it's it's oh but doesnt oh yeah, yeah, yeah, yeah, yeah, and right and there's a similar. Um. I organoid thing where cells that form into what would be is there sorry cells that make up what is normally like the optic cup that has this kind of concave shape you know in in our 3 DPetri dish also adopt like a curved Shape. So I mean it's so.

  20:46.78

  talknerdy

  Ah, so cool.

  20:55.61

  Raghuveer

  This is very much kind of an open question and sort of ongoing. But yeah, what aspects of things like organ formation are sort of the the necessary complex biochemistry and what parts are okay, the cells responding to particular cues have particular properties and then because of that they assemble themselves into particular forms.

  21:13.44

  talknerdy

  Yeah.

  21:15.14

  Raghuveer

  And we don't know in a deep sense or in a thorough sense the answer to that. But it's it's becoming really clear that it really is a mix of those 2 things there is um, yeah, there is some complicated biochemistry and stuff but there really is self-assembly even at these higher levels of organization of like whole organs.

  21:28.50

  talknerdy

  I Mean there must be it it it sort of really does throw this massive paradigm shift into the view of Developmental Biology I Think so often people look at um, ah.

  21:39.30

  Raghuveer

  Yes.

  21:45.46

  talknerdy

  Ah, genetic abnormalities or developmental abnormalities and they focus on look at what went wrong look at what went wrong, but very often I think the real question is look at all this stuff that went right in spite of the fact that this went wrong like this 1 thing misaligned or miscalculated or miscoded or whatever but everything else.

  21:54.64

  Raghuveer

  Um, yeah, yeah.

  22:04.16

  talknerdy

  In a very resilient way built up around it as if that thing wasn't wrong and that happens a lot.

  22:06.60

  Raghuveer

  Right? Yeah, yeah, and you know we've had hints of this for a very long time. There are these you know classic studies of early development of biology about ah probably been over one hundred years old where people did things like taking cells. From like an early stage like so starfish embryo or sea ocean embryo or things like that and you know if you took a particular subset of cells you could regenerate the entire organism from just a piece of it or you could you know move things around from one part to another and depending on the timing and things like that.

  22:36.60

  talknerdy

  E.

  22:44.67

  Raghuveer

  Would have things that could actually yeah grow up into into the correct thing just based on the kind of structural cues from their neighborhood.

  22:51.10

  talknerdy

  Yeah I did that when I was I remember um in middle school I think if we were in eighth grade my partner and I Ashley Reid shout out. We did a um science fair project and like we won you know something like second place at state or regionals or something. Um.

  22:56.62

  Raghuveer

  And ah.

  23:05.96

  Raghuveer

  Wow.

  23:09.61

  talknerdy

  And ah yeah, it was with flatworms Planaria because you can legit cut them in half and they just reassemble which is a really cool. Um, so yeah, we would teach them a maze and then we'd cut them in half and see if both halves knew the maze. Um and it was a really cool experiment to see. Um.

  23:11.10

  Raghuveer

  Um, ah yeah.

  23:27.40

  talknerdy

  Like a fun thing that you know very young curious scientists could do but ah, there's a million ways that you could look at that data and um make some pretty interesting inferences and really have some of these more philosophical conversations about what that means.

  23:39.84

  Raghuveer

  Yes, yeah, yeah, yeah, yeah, very much. Um, it's interesting also like I mean the the philosophical side of it comes up in like a lot of different ways in like contemporary things you know, related to ethics and stuff like that. But even in a lot of these these older things. 1 of these pioneers. Ah, it's a story I put into chapter on on development in here. But um, I'm very bad with remembering names I have to even look back at what I wrote. But yeah.

  24:04.46

  talknerdy

  E. Same same same? Yeah, always.

  24:13.97

  Raghuveer

  So you know one of these people. Ah Hans Tresch who is a german biologist working in italy he realized yeah you could take um you know a cell from a early stage sear and embryo move it from its normal position to a different 1 and despite that shuffling the sea urchin would develop like normally yeah, it's it's as if the transported cell you know knew its new environment and acted accordingly became you know the mouth instead of the whatever else and he was so freaked out by this.

  24:40.16

  talknerdy

  Yeah, ah man.

  24:45.56

  Raghuveer

  That he actually abandoned the study of developmental biology and became a philosophy professor because he felt you know there's no way we can make sense of this. You know it's telling us that you know we should give up and yeah, thankfully other people did not give up and.

  25:01.00

  talknerdy

  That's amazing.

  25:01.83

  Raghuveer

  And the field of development of biology did not come to a dead end but it was you know, even at the time it was really kind of clear that this is this these are deep things this notion of like self-assembly and like what can and can't it give you and so on right.

  25:11.80

  talknerdy

  Yeah, and of course it's it's it's one of 4 that you I don't want to say arbitrarily because it's not arbitrary like you really dug deep into sort of your own I guess your own taxonomy of this. Um.

  25:20.50

  Raghuveer

  Yeah, my yeah it is fair to say it's not like a canonical set of 4 I like it's it's my set of 4 but it's but it and you know you probably get different different lists from different biophysicists. But yeah.

  25:28.14

  talknerdy

  Yeah. Well and to be fair even Canon is um as as I've spoken about often on the show and and I think more specifically when I had Lulu Miller on the show to talk about her amazing book. Why fish don't exist. Um the idea of yeah, it's it's.

  25:48.13

  Raghuveer

  I've heard of that It's on my on my list. Yeah.

  25:50.33

  talknerdy

  Ah, it's incredible, but it really grapples with the idea of you know Taxonomy categorization that even canon even things that we think of as being like almost law. It's still constructed. These are still ideas that human beings are grappling with observations and trying to to.

  25:53.20

  Raghuveer

  So.

  25:58.49

  Raghuveer

  Um, yeah, yeah.

  26:09.63

  talknerdy

  Categorize these observations and so there's always still going to be some amount of bias whether it's generational bias whether it's you know it's like this very sort of structure of you know cuny and like structure of scientific revolutions like there's always going to be something built into it and so your 4 categories.

  26:21.58

  Raghuveer

  Um, in this pivot.

  26:27.56

  talknerdy

  Are probably I mean ah objectively obviously they are meaningful but also deeply meaningful to you because of the work that you've done and and how you have sort of um, developed your own relationship with biophysics. Um, yeah.

  26:42.17

  Raghuveer

  Yeah, yeah, yeah.

  26:45.97

  talknerdy

  So so self-assembly one that I think makes a lot of sense to me sort of intuitively. Although it probably is a very complicated thing if it's the first time you've heard of it but 1 that doesn't make that much sense to me intuitively is um the idea of regulatory circuits. Yeah, this one I think I need a little more help with.

  26:53.17

  Raghuveer

  Bright pink. Ah, good. Yeah yeah, yeah, this this might be the most kind of abstract of them. But yeah, so here I think a good way to start out thinking about this is is um. These days you know everybody even if they can't really define. It. Everybody's sort of genes. They know that you know genes in some sense are these you know pieces of information that that are carried along in our by our Dna. Yeah, even if they can't sort of precisely say what's there, but there's this this kind of remarkable thing that first of all.

  27:26.55

  talknerdy

  E.

  27:33.75

  Raghuveer

  You really don't have that many genes you have depending on how you look at at you know Twenty Thousand Ish genes so that's 20000 kind of instructions that a cell like 1 of your cells houses it at its disposal like 20000 different proteins. It can make.

  27:44.96

  talknerdy

  Yeah, it's actually it's ah it's a big number. But when you think about how complex we are as species. It's.

  27:49.82

  Raghuveer

  Exactly? Yeah, yeah, it is a big number. But yeah, when you you put it very well when you think about all the different things that you do you know from digestion to immune responses to vision to hearing all you know 20000 is not that big. What's more.

  28:01.46

  talknerdy

  Yeah.

  28:05.41

  Raghuveer

  Your skin cell like you know one of your skin cells has exactly the same genes exactly the same genome as one of your neurons and it's the same genome. That's also in you know one of your muscle cells and so on but clearly these are doing different things so that in itself tells us you know there's some higher level of complexity here and.

  28:10.33

  talknerdy

  Right.

  28:24.80

  Raghuveer

  What a lot of that is is basically turning particular genes on and off at different times and also in response to other things so to be a bit more concrete with that. Let's imagine and this is sort of 1 of the the classic examples you are a bacterium and you're swimming around. And you want to eat sugars and the sugar and so you have a gene that encodes for a protein that digests that sugar. So that's great if you turn on that gene you get that protein you can digest that sugar. But. It costs energy to make that protein. You don't want to be doing if there's no sugar around. So what do you do? Well one very common tactic is you have something that blocks that gene from being turned on. But that thing that blocks the gene from being turned on can also bind. That sugar and if it's bound to that sugar. It's not going to block the gene. So if he find the sugar exactly there's a signal and there's this kind of circuit if I if I find the sugar I stop blocking the gene I turn on that gene and I make more of the proteins that will digest that sugar. So it's kind of.

  29:20.54

  talknerdy

  Right? So now there's a signal. Yeah yeah.

  29:32.88

  talknerdy

  I see so you're seeing this as as almost like an electrical circuit this sort of biological circuit. Okay, okay.

  29:37.87

  Raghuveer

  Exactly? Yeah, yeah, yeah, exactly exactly and it and it's not.. It's not even that I guess I've way to put it. It's actually you can be a pretty exact analogy Even so you know you have these things that can regulate whether like genes are turned on and off. And what's more they can do actually the same sorts of operations that like electrical circuits do so inside your computer and yeah or little logic gates. Actually yeah yeah, because you know in your computer you have something that is you know turning on a voltage if this signal is on and that one is off so you have this you know.

  29:59.41

  talknerdy

  Right? So they're like little resistors or little capacitors. Yeah yeah, okay.

  30:12.57

  talknerdy

  E.

  30:14.73

  Raghuveer

  Language of ones and zeros and circuitry that says. Okay, if this is a one and that's a 1 make that a 0 or if that's a 0 and that's a 1 make that a one you know all these these combinations of and and or and stuff like that that all together can like kind of synthesize different inputs and make different decisions. Well it turns out this.

  30:18.43

  talknerdy

  Name.

  30:33.22

  Raghuveer

  Kind of circuitry of am I turning on Genes and turning off Genes can do the same things you can have things where if I have sugar a and sugar B then I'm going to turn on this sugar digesting protein. But if I have sugar a and sugar B isn't there then I won't.

  30:42.43

  talknerdy

  Right? right? right? because I can like metabolize that one way easier and I don't need this whole Murka truth more I Love that.

  30:50.90

  Raghuveer

  Oh exactly, exactly exactly? Yeah so you can make kind of preferences and decisions you can make you can do basically computing and even the simplest bacterium. It turns out does this which is really cool and which like it also points out a way that complexity is generated from simplicity.

  30:56.86

  talknerdy

  Yeah, right right.

  31:09.89

  Raghuveer

  Just like your computer doesn't need. You know there's not like a thousand different types of transistor. It just needs 1 type but with lots of connections between them that can make these kind of regulatory calculations. You can get a lot more out of the machines you have by doing these combinations of of things.

  31:24.66

  talknerdy

  Yeah, which again sort of like goes back to this idea of like what is the most efficient like what is the least amount of energy that I need to use to be able to like do this biological process.

  31:31.20

  Raghuveer

  Right? right.

  31:37.59

  Raghuveer

  Yeah, that's a good way of thinking about it because yeah, yeah, because now if you flip that R and say okay if I didn't have these circuits. What would my genome have to look like how massive would it have to be to I know Yeah, there would be room for the rest of me there would be like yeah.

  31:44.72

  talknerdy

  Yeah, it'd be like the constitution with like a million amendments added to it's like oh gosh exactly? yeah's and this also goes to goes to I mean the thing that sort of comes up for me in my weird brain that has a lot of weird connections is that.

  31:56.64

  Raghuveer

  And yeah.

  32:04.40

  talknerdy

  Is this never ending like debate or discussion that you always hear about nature versus nurture and it's like it's both like this is such an example of it's both. You have these genetic instructions that only go into effect if and when you are have you encounter something in your environment.

  32:08.62

  Raghuveer

  Oh right right here? yeah.

  32:19.29

  Raghuveer

  Exactly So both things exactly exactly? Yeah yeah.

  32:23.55

  talknerdy

  Yeah, yeah, and and that's everything from the type of personality you'll develop as an adult to the way that a bacterium metabolizes the sugar.

  32:28.70

  Raghuveer

  And event. Yeah and you have like feedback through all these and like you know you can put yourself in 1 kind of state of a circuit and just stay there stably until you get a signal to go into like another state and this relates to things like memory and and stuff.

  32:44.64

  talknerdy

  Yeah, totally it. It really does have a lot of explanatory value across multiple constructs everywhere from like the complexity of the sort of.

  32:46.39

  Raghuveer

  And as well. Yeah.

  32:57.47

  talknerdy

  Human or Mammalian brain. But even down to like these very basic ah Metabolic kind of processes. Yeah.

  32:57.64

  Raghuveer

  Right? right? Yeah India so this one is again one that kind of cascades across scales like you know it's relevant to kind of how bacteria or even other single cells work. But also you know broader things like organs and.

  33:15.30

  talknerdy

  Yeah, yeah, which is funny because oh no, no, you go ahead? Sorry I'll make it out.

  33:17.32

  Raghuveer

  What we get some one of the coolest circuits is you can do timer oh sorry, good. Okay, 1 of the coolest things is that you can almost anything you can think of making as an electrical circuit you can make as a biological circuit and in many cases nature does like you can have things where like 1 gene affects another affects another. In like a rhythmic sort of cycle so you can make ah a clock something that you know rhythmically expresses itself and people have built these artificially for various biotechnological purposes. So you can have something that like glows green periodically every minute or something but then your your like nature makes used to this as well. So.

  33:38.14

  talknerdy

  E e.

  33:54.10

  Raghuveer

  Things like the regularity of like the spacing of your vertebrae are actually because of irregularity and time of a clock that was going on when you inert when when you were an early embryo that was like synchronizing certain activities happening with like periods of growth.

  34:07.92

  talknerdy

  Oh yeah, yeah, it's funny. You mentioned that people might like it code or like develop. Ah you know something that glows like every minute or whatever and like the first thing I thought of was the little dyno ah flagellets that I have in my office these little like algae that actually glow.

  34:22.10

  Raghuveer

  Um, ah oh yeah, yeah yeah.

  34:27.46

  talknerdy

  Um, you know they buy a luminesque but only at night and and and when you first get your shipment. They say you know make sure it's in a room that gets plenty of light but also goes dark at night because they need to resync back to their clocks like you can't just always have them in the dark they'll.

  34:39.29

  Raghuveer

  Exactly yeah.

  34:44.46

  talknerdy

  Die They'll lose their capacity or if they're always in the light. They'll never glow. But if there's a cycle they will readapt to it which of course you know we all know as the Circadian cycle that we that we know love and and sometimes don't love so much. Yeah, and of course there's so many examples of that throughout.

  34:51.63

  Raghuveer

  Um, exactly? Yeah yeah, right? exactly.

  35:03.94

  talknerdy

  Um, throughout like all of biodiversity. Not just in terms of you know Circadian types of intrinsic clocks but ah pacemaker cells and you know just like there's so many examples which is how cool.

  35:11.79

  Raghuveer

  Of course, yes, right? Yeah, yeah, yeah, there's even you know example spanning Organ Spanning organisms like there are these ah fireflies that will like synchronize together and all like flash at the same time. Just beautiful videos of this.

  35:25.28

  talknerdy

  Ah, that's so cool. Yeah, the like all all that sort of really neat like um, hive mind research like looking at kind of bees and cooperative movement and and communication with bees and looking at like murmurations of birds and insects and things it's like.

  35:29.21

  Raghuveer

  Yeah I think they're then in Malaysia or something like that. Yeah.

  35:40.94

  Raghuveer

  Right isn't.

  35:44.69

  talknerdy

  Super fascinating and and must be fundamentally important and interesting to people who study biophysics and material science. Yeah.

  35:49.80

  Raghuveer

  Yes, yeah, yeah, and and that's been that area of like kind of flocks. And yeah, these kind of collective ensembles of organisms is one. That's really taken off in the last kind of 10 years or so especially because like tools for observing these have gotten so much like.

  35:55.46

  talknerdy

  M.

  36:07.64

  Raghuveer

  Better and cheaper. You have like arrays of cameras that you know, watch your starlings flying around and and it's really beautiful exactly. Yeah yeah, yeah.

  36:11.28

  talknerdy

  Yeah, oh I love it. Yeah, there's like a lot of kind of big data in Citizen science that can be cool and so it's it's interesting because you mentioned with regards to regulatory circuits. But I think it also applies to self-assembly that it's something that kind of happens across.

  36:27.97

  Raghuveer

  Yes, oh yes, Yep yeah yes, yeah so um, short answer is yes.

  36:29.10

  talknerdy

  Scale and it's funny that you say that because one of your um, one of your 4 principles is scaling but before we get to scaling is predictable randomness. The third also something that occurs across scales. Okay.

  36:46.57

  Raghuveer

  But the the kind of most important manifestation of it is really microscopic so here well sort of first of all in in a broad sense. What I mean by this theme is that there are a lot of things in the living world that are random and nature actually makes use of that randomness and the fact that.

  36:49.60

  talknerdy

  Okay.

  37:06.90

  Raghuveer

  Something can be random but still have kind of well-defined properties on average. So the kind of most um, most important and maybe even most fundamental manifestation of this is something called brownie in motion which a lot of people think have seen in like high school but basically what it is is if you look in a microscope.

  37:09.70

  talknerdy

  Okay, yeah.

  37:18.94

  talknerdy

  Oh yeah, yeah.

  37:25.65

  Raghuveer

  Just a little specks of dust or something like that like in water you'll find that they're always jiggling around and this it turns out is something you can just you know again, go to just a little tabletop microscope and see that stuff is never still. It's jiggling around but it turns out it's one of the like deepest phenomena in the universe. It's really amazing. Um, and it was actually something discovered by a biologist a botanist Robert Brown in in the nineteenth century who realized yeah he he was looking at actually these little specks inside of pollen grains and found that they were jiggling around and he did these beautifully careful experiments that established that this was not because of anything to do with life. But just because that's what stuff did that fundamentally things bounce around. Yeah exactly and the smaller something is the more relative to the size that it's bouncing around and so big stuff. You know you don't see your yet exactly.

  38:03.50

  talknerdy

  Right? Things bounce around if there's if there's space to do it. They'll bounce around.

  38:13.67

  talknerdy

  Right? And this is this is fundamental to diffusion osmosis. It's fundamental to how drugs work It's fundamental to everything.

  38:22.49

  Raghuveer

  Exactly exactly and so nature because this is just everywhere You can't You can't get away from it nor do you actually really want to get away from it. So There's all sorts of things where nature takes something puts it nearby where it needs to go and then relies on this random. Um, chaotic motion to do the rest like neurotransmitters. Yeah.

  38:40.64

  talknerdy

  Right? to just let them bind like eventually something will fall into a spot that it fits in.

  38:45.59

  Raghuveer

  Exactly exactly so like you know, right now in each of us. You know we have these chemical synapses that are sending signals between like neurons in our brain you have like 1 neuron and then a little gap with fluid and then another neuron and that first neuron just releases some neurotransmitters into that little gap and they have to get to the to the. The other neuron and you know you might think there's some little ferry system or cables or whatever that do it. But no, they're just there in that space. They'll jiggle around and you know randomly at some point some of them will get to the other one and that's that's the signal so you again, don't have to like hardwire everything or or.

  39:08.10

  talknerdy

  Yeah.

  39:18.62

  talknerdy

  Yep.

  39:23.30

  Raghuveer

  Have a little machine that exactly puts everything in its Space. You can rely on these random behaviors and the fact that you know if you know how big little particles are and what the spaces they need to go Across. You can predict on average how long it'll take a signal to get across and that's a perfectly good. Perfectly Good average. Yeah.

  39:44.32

  talknerdy

  You're right? But it's always a prediction and this is I mean just just as like another example to be clear because this is something that always makes me crazy when there's a bit of a lack of understanding about this. This is why drugs have side effects because when you swallow.

  39:55.35

  Raghuveer

  Um, oh yeah, yeah yeah.

  40:00.14

  talknerdy

  Medicine and these little molecules go all through the body. However, the route of administration allows them if they go into the bloodstream if they you know there's different routes but wherever that medicine ends up. It's going to bind to whatever it binds to and sometimes it's the target and sometimes it's not what we were going for which is why sometimes.

  40:12.16

  Raghuveer

  Yeah, yeah.

  40:19.99

  talknerdy

  You know, especially I think of things like Chemotherapy um because I work I work as a therapist in a cancer center. So I see this a lot and very often. Ah, one of the biggest um concerns that I'll hear from patients as they change drugs is they'll say I'm not as sick on this drug or this drug doesn't make me feel as bad. Maybe it's not working.

  40:23.38

  Raghuveer

  Yeah.

  40:35.49

  Raghuveer

  A is is it.

  40:37.86

  talknerdy

  And it's like just because it has fewer side effects doesn't mean it's action. Its activity is lessened but we're so used to thinking that way. We think that the side effects are something that happen downstream to the to the mechanism of action. But that's not what a drug is a drug just binds where it's going to bind.

  40:43.63

  Raghuveer

  Yeah.

  40:49.38

  Raghuveer

  Right? Yeah, yeah, well and I think even more broadly people Somehow we are. We do a poor job educating people about randomness in general.

  40:55.39

  talknerdy

  Because it's just moving around.

  41:03.60

  talknerdy

  Um, yes when everything is right? I mean this is this is what stoke.

  41:05.77

  Raghuveer

  Like there's a real resistance to believing that randomness exists. Ah yeah, yeah, yeah, yeah, yeah, exactly yeah, exactly exactly and just realizing you can have ah you know.

  41:13.70

  talknerdy

  Like the stocat the principle of stochasticity like I Love this word stochastic. It's that everything is random but maybe kind of predictable but also random. Yeah.

  41:23.88

  Raghuveer

  Exactly the same conditions and just you know variation in in what the output is that's a real eye opener to a lot of people I teach a lot of like science. Yeah classes for non-science majors and which is a lot of fun but that's one of the things that really takes of work and is really kind of a revelation to a lot of people.

  41:28.53

  talknerdy

  Yeah, yeah, this idea too that mm. Um I think for for me. Um it a lot of this came to fruition not from my science training but from my statistics training that when I Really yeah, started to grapple with cognitive biases around things like just.

  41:51.70

  Raghuveer

  Um, ah, interesting.

  41:58.71

  talknerdy

  Straight up probability and flipping a coin that if just because I got heads 3 times in a row. It has no effect on what happens next but we we as you know psychological creatures want to think that these things are all.

  42:04.28

  Raghuveer

  Um, ah.

  42:13.28

  Raghuveer

  Name it.

  42:13.76

  talknerdy

  Related to 1 another that. Oh I you know I'm going to break a streak. It's why gambling you know works right? It's why people drop so much money in vegas um, but the more that you really grapple with I think probability I I believe that the better your sort of appreciation for scale.

  42:28.87

  Raghuveer

  Right.

  42:30.66

  talknerdy

  For randomness for the sort of what actually truly is connected and what's not like just the difference between drawing a card with replacement or not right if I'm going to draw a card out of a deck 10 times in a row but the card is not replaced in the deck. It's going to complete.

  42:41.30

  Raghuveer

  Right? right.

  42:48.22

  Raghuveer

  Very different. Yeah.

  42:49.16

  talknerdy

  Completely change my odds? Yeah and I don't know I also love poker and so maybe that's why all this stuff kind of speaks to me but I do think that sort of oh oh hell yes, that's actually another book that I've recently had not recently now but Maria Konnikova come on the show to talk about.

  42:53.62

  Raghuveer

  Ah I see I should that probably gave you better better handle on statistics than a lot of things. Yeah oh I read that? Yes, yes, the confidence game you mean.

  43:08.86

  talknerdy

  It's so good right? and these these fundamental. Yes, the confidence game and oh actually no she've done another one since the confidence game confidence game is also great. Yeah, that's the one that she wrote pre-trump but like a lot of it's about trump right isn't the confidence game. The one about um, ah or maybe this is her poker one.

  43:13.50

  Raghuveer

  Yes, yeah I wrote the album hope Oh no.

  43:23.20

  Raghuveer

  Ah, it's been awasis right.

  43:27.13

  talknerdy

  No, the confidence game is the one about con artists. Yeah yeah, which is so good. Yeah, that was like the book that put her on the map but she also did a recent book. So I mean long story short I'm not going to let Maria's episode co-opt our episode but she she decided to for a book learn how to play poker and then she ended up like winning a.

  43:28.13

  Raghuveer

  Exactly to a common artist. Yeah.

  43:36.47

  Raghuveer

  Ah.

  43:46.10

  talknerdy

  At the world's series because she's so freaking good and so she wrote um, a book called the biggest bluff and it's literally all about these fundamental poker principles and and chaos theory and stochasticity and like how they sort of explain a lot of first principles which I think is really cool and.

  43:49.91

  Raghuveer

  I think.

  44:01.77

  Raghuveer

  Right.

  44:04.58

  talknerdy

  Speaks a little bit to even this I mean I don't think she really goes there much in the book with like biology but that this kind of biological. Um, ah predictability is all a function of probability because of randomness.

  44:15.84

  Raghuveer

  Yeah, yes, and I mean the other place this comes up That's you know, extremely important just for like current society is an under thing understanding things like genetic diseases and so I spent a while a while on this this in the book. You know we have you know there are various disorders that are.

  44:26.92

  talknerdy

  Right.

  44:35.83

  Raghuveer

  Really, you know the fault of 1 gene like cystic fibrosis or something like that. But then there's a lot of things. A lot of traits both good and bad and and ah even some things as kind of innocuous as like height that are that seem to be the manifestation of like thousands of different genes.

  44:36.93

  talknerdy

  M.

  44:51.56

  talknerdy

  Right.

  44:55.30

  Raghuveer

  And so there's I mean you can almost think of them as like thousands of coin flips and you have some kind of random ensemble of these and some kind of average probability that they that they give you you know for a particular height or something like that. But there's a variation around that and so. Understanding. You know what can and can't you do with these sorts of things really does require having a ah decent grasp of you know what does randomness mean and yeah, what can we say and not say.

  45:23.59

  talknerdy

  You're so you're so right and I think for anybody who's like engaged in a consumer um, genetic testing product which you know you can. We could have a whole separate conversation about the ethics of you know, sending sending off your entire genome to ah.

  45:35.13

  Raghuveer

  Music system.

  45:40.97

  talknerdy

  Corporation. Um, and then like it and then them coding it for you but but ah, there's something cool about like I remember doing 23 in me and early on in the days like the sort of readouts were a little bit more crude but now there's just there's so much education built into the platform and and 1 of the things that I think is so cool is that you know each.

  45:46.85

  Raghuveer

  Um, is it.

  45:56.19

  Raghuveer

  Yeah, and.

  46:01.20

  talknerdy

  Trait that they're describing is a prediction they describe it as a prediction and what I love is when they get it wrong because it really shows you like my 23 and me says I should likely be blonde which blows my mind. So my genes are are basically if you just read my genes.

  46:01.50

  Raghuveer

  Right? You know? Yeah yeah.

  46:11.85

  Raghuveer

  Ah.

  46:18.20

  talknerdy

  My genotype not my phenotype but my genotype it's saying probably maybe she'll be blonde and my phenotype's like black hair. You know it's like there's no way and I love that because it goes to show that this is a probabilistic calculation.

  46:22.38

  Raghuveer

  Yeah, yeah.

  46:28.28

  Raghuveer

  Exactly? Yeah, yeah, and I think having this information is great I'm I'm actually quite optimistic about what we can do with that and so on but like yeah I think you know if if 1 you know if if somebody went into this thinking? Oh it's predicting I'm going to be blonde.

  46:34.69

  talknerdy

  In here.

  46:45.80

  talknerdy

  Right? And that's where it gets dangerous when it says yeah like these you have these markers for this disease that doesn't mean you're going to get it but you might have a higher likelihood and and then it becomes a risk benefit calculation very often like what I.

  46:45.91

  Raghuveer

  That that means there's a hundred percent chance I'll be blonde. You know that's the thing we have to educate against. Yeah yeah, right? exactly.

  47:02.35

  talknerdy

  Do with my patients like I work with a lot of patients in end of life or in recurrent situations where they're really grappling with the extension of life using Modern medicine and quality of life and sort of it's a complex algorithm that we have to determine and I think it's the same thing with genetic um, counseling right? This idea that.

  47:10.83

  Raghuveer

  Yeah, right.

  47:19.60

  Raghuveer

  Exactly? Yeah yeah.

  47:22.70

  talknerdy

  If the disease is more severe and if the likelihood is is higher then the calculation becomes different than if the disease is less severe and the likelihood is lower. Yeah interesting. So so give me another example then of of the way that predictable randomness I mean we talked about brownie in motion. So like.

  47:28.64

  Raghuveer

  Exactly Yes, Yes, yeah.

  47:41.59

  talknerdy

  Basic atoms you know or small molecules are like buzzing around everywhere and then you know it it continues but as things get larger right? Like you said it's It's a little bit less obvious but are there examples of like macro scales of this.

  47:54.53

  Raghuveer

  Oh that's a good question I mean Macro Scales um almost more by analogy like things like having like we were just talking about like multiple genes that are all contributing ah a small amount to one phenotype essentially giving you ah, a sort of predictable randomness too.

  48:01.76

  talknerdy

  E.

  48:07.13

  talknerdy

  Right.

  48:14.34

  Raghuveer

  To an overall trade and things like that that is where I see more of the how that theme manifests itself at at the larger scales I mean it is true that you you know I should point out you know in other context like turbulence in the ocean waters. You know how whales feed and swim and stuff like that affects things and.

  48:14.89

  talknerdy

  Right? Yeah, yeah, that makes sense.

  48:32.20

  Raghuveer

  There's you know, randomness associated with large scale fluid flows and stuff like that. So there is you know that sort of thing. Also yeah.

  48:33.46

  talknerdy

  Oh you're right? and even cosmologically probably there's I mean I bet you cosmologists often have to kind of calculate in a a error bars on you know this supernova or these two you know things colliding or whatever because.

  48:47.20

  Raghuveer

  Um, of course. Yeah, yeah, yeah, yeah.

  48:52.18

  talknerdy

  Because of that it's like well it's predictive and it could do this and it could do that. It's um, you know, but based on if it does this then it'll determine whether it does the next thing I Love it I Love it So good. Okay, so so the last one of course that you mentioned is is.

  48:58.91

  Raghuveer

  Right? exactly? So yeah, yeah, yeah, definitely.

  49:09.38

  Raghuveer

  Um, yeah.

  49:10.54

  talknerdy

  Scaling and I think scaling is it's sort of its its own animal in a way like its own beast because it it applies to the first 3 and then some so so give give us a little lowdown on scaling.

  49:19.50

  Raghuveer

  Yes, yeah, so what we mean here is just the idea that um thing like the the importance of different physical forces can be different at different sizes and this seems um.

  49:31.49

  talknerdy

  E.

  49:36.38

  Raghuveer

  Kind of obvious but it's 1 where again if you kind of think about it. It makes a lot of things make sense like for example, you know you look at an elephant and it has really thick bones and it's not just that it has thick bones. Um, you know if you could Compar like an elephant and a cat. It's not that the elephant is for up near.

  49:55.10

  talknerdy

  Right? m.

  49:55.73

  Raghuveer

  10 times taller and its bones are 10 times wider. It's 10 times taller and its bones are 20 times wider that's disproportionately thick bones and we could see things like this all over the place that that things you know property seem to depend on size and so you can ask. Okay, why is that and so it's because the this idea that different. Forces scale differently. So like coming to to the elephant. You know what's the elephant leg trying to do. It's keeping the elephant up so we have like gravity pulling the elephant down and that force of gravity depends on the the mass of the elephant like the total volume of elephantness that you have and. Um, so that depends on this volume of the elephant. But how strong a bone is depends on its area like the cross-sectional area and this isn't just particular but to bones this is sort of the thing that's true about beams whether they're concrete beams or or whatever yeah scaffolding a general 4.

  50:45.84

  talknerdy

  Okay, so like scaffolding in general requires okay all right.

  50:52.30

  Raghuveer

  I mean there's different ways. Things can fail. But at least if you're squishing something kind of Lengthwise. It depends on the area there so you can imagine let's suppose you you took an animal and you made it twice as wide twice as deep twice as tall you would make it 8 times as massive so 2 times 2 times 2 but its legs like its area would be just 4 times bigger and so if you just kept everything proportional like the size of its legs being the same proportionality to its body as as would normally be the case. It would be getting more massive and have more of a force of gravity than the.

  51:14.19

  talknerdy

  E.

  51:31.60

  Raghuveer

  Force of its bones could withstand so your animal would collapse exactly? Yeah, so just just this basic thing that like gravity depends on the mass of an object and the bone strength depends on the area.

  51:31.88

  talknerdy

  Oh yeah, it would be recipe for osteoporosis. It's just like terrible.

  51:48.13

  Raghuveer

  That automatically tells you that bigger animals are going to have to have disproportionately thick bones to keep up with that extra mass and so that it turns out is what animals do bigger. Oh so that's right? So that's a beautiful question. So the answer is sometimes.

  51:52.18

  talknerdy

  Right? And do they scale predictably like I know it's not linear but is it like logarithmic. Okay, all right.

  52:07.52

  Raghuveer

  If you look at particular families of animals and I I give things like Attelopes and willdo be some these so-called bovids as an example in the book. They actually do scale with the proportionality that makes their bones keep up with their mass. So it turns out that.

  52:20.39

  talknerdy

  Okay, and that sort of makes sense from an evolutionary perspective because they've yeah yeah.

  52:24.99

  Raghuveer

  Exactly they have similar kind of lifestyles and behaviors. The antelope runs along the willerby sp runs runs along the little tiny dick dick runs along. They're doing similar things so they they they scale their bones to make this to make these physical forces work out in the same way.

  52:39.30

  talknerdy

  Right? But like bird bones are inherently different from Antelope bones though. Yeah, you're going to see a different scaling.

  52:42.69

  Raghuveer

  Yeah, exactly exactly? Yeah, so if you cross to different sets of things and even the elephant its bones are thicker but they're they're still not actually as thick as they would have to be to have the kind of relative strength of of an antelope. So exactly. So if you've ever wondered. You know why can't elephants jump.

  52:53.45

  talknerdy

  Oh yeah, right? because they don't bound. Yeah.

  53:01.15

  Raghuveer

  It's because if they were if their bones were strong enough to support them jumping their bones would have to be like like twice as big as they presently are and they basically just be all bone and be a horrible way to to live as an elephant.

  53:09.20

  talknerdy

  You know what's you know? It's so funny. This is like the weirdest little anecdote but I remember spending time in Namibia and being at a reserve and being outdoors in in this area where the lodging was and it was sort of on ah an elevated. Um, like it like terraced ground and there were all these. We're very lucky that we were in this place where there's so much wildlife and and the only animals that would come up to where the lodging was were Antelope um, ah baboons and. Um, like a couple of kind of annoying critters. But but there were big scary animals out there. There were like massive elephants and massive rhino and it was like they were right there and I was like oh my god they're going to come here and it's like nope they can't they can't climb up that little lip like they literally can't get up here.

  54:00.90

  Raghuveer

  Um, oh yeah, yeah, and yeah, yeah, yeah, they don't jump. Yep yep.

  54:06.13

  talknerdy

  Because they can't lift their legs high enough and they don't jump and it was It was amazing to see like they can leave they can rear up on their back legs to reach things in trees. But then they can't use their front legs to continue the the motion so I was right there so close to these horrifyingly dangerous creatures but doesn't matter because they can't like.

  54:12.98

  Raghuveer

  Yeah, and just using. Yeah.

  54:22.75

  Raghuveer

  They catch up here. Yep, yeah yeah, it it is. It is pretty remarkable.

  54:24.82

  talknerdy

  They can't climb like six feet it's amazing

  54:31.76

  talknerdy

  So okay, so this idea that scales happen Dis somewhat disproportionately sometimes proportionately but sometimes disproportionately obviously becomes important for things like um, ah Quantum mechanics right? like this is ah a whole new version of.

  54:47.47

  Raghuveer

  Oh that's true. Also, Yeah, yeah, yeah, that's it Yeah right? exactly? Yeah yeah, and yeah, so this is actually kind of a ubiquitous theme in a lot of physical things just like you know the yeah the importance of different forces or different phenomena.

  54:51.17

  talknerdy

  Scaling like things get super weird when they're really small or really big.

  55:06.30

  Raghuveer

  Have different dependencies on size so they're kind of balanced with each other yet depends on depends on scale and and then the the challenge is to kind of understand. Okay, what is the underlying reason for that that scaling behavior that we observe so like in the example I gave you know we we can see that the bigger animals have disproportionately thick bones. What is that telling us and it's telling us about the and this interplay between like gravity and strength. But you you can observe that scaling and then can you can you make sense of it.

  55:32.88

  talknerdy

  I Love that and you know it. It's sort of for me. It has explanatory power like really simple explanatory power and this is coming from a nonphysicist so you tell me if I'm like off off the mark here between sort of Newtonian physics and.

  55:44.38

  Raghuveer

  Um, get this.

  55:51.47

  talknerdy

  You know einsteinian or or sort of like newer modeling of things that like when Newton and when like sort of early basic physics was first being described. It was very much based on a human scale like it was very much based on what we could observe with the tools we had that were earthbound.

  56:02.10

  Raghuveer

  Yeah, well.

  56:08.30

  Raghuveer

  Yeah.

  56:09.90

  talknerdy

  And then things started to get more complicated when we realized that like other parts of the universe have different gravity or they don't have different gravity. The force is the same but but we measure differently because of the mass of the objects in it. It's bent differently and Spacetime is different and and so we had to start thinking about all these things in ah in a way that was more complex.

  56:15.29

  Raghuveer

  Yeah, yeah, yeah, yeah.

  56:26.66

  Raghuveer

  Yeah, right I mean that's totally true. It's interesting. You don't even have to go to quantum mechanic for that like going back to like predictable randomness and brownie emotion. You know that's not even quantum mechanical but it's away from kind of our human scale of everyday experience so we don't actually have a.

  56:28.52

  talknerdy

  Because we weren't just operating on the human scale.

  56:37.25

  talknerdy

  Mean.

  56:46.25

  Raghuveer

  We We're not born with a good intuition for the fact that everything is jiggling around because just it's so foreign to our to our experience.

  56:51.40

  talknerdy

  You're right? Yeah and this is something we talk about a lot in sort of the skeptic movement and you know neuropsychological humility is that we evolved to exist on a planet with.

  56:57.27

  Raghuveer

  You may be right right.

  57:05.83

  talknerdy

  Green plants and with you know, food sources that were here here and here and with predators and Prey and like we we evolved a lot of our basic sort of quote instincts or or tendencies on Planet Earth with these pressures.

  57:19.97

  Raghuveer

  Yep, exactly yep.

  57:21.29

  talknerdy

  And and we evolved that way and then they don't always serve us. They help us survive. It's like um god I just brought this up the other day. It's like um, ah Robert Sapalski's famous book. Why zebras don't get ulcers right? like zebras never developed chronic stress like human beings did.

  57:30.83

  Raghuveer

  Um, oh yeah, yeah yeah.

  57:39.70

  talknerdy

  But like all of our biological and psychological machinery that we evolved over hundreds of thousands of years like didn't really anticipate being in a stressed out situation for longer than a few minutes you know and and so all bad stuff happens now because we've kind of messed with that scale a little bit.

  57:48.33

  Raghuveer

  Right? right? is. Yeah, it is really amazing. How like the scales we're we're used to.. It's just it. It takes real work to like you know, internalize The fact that there's all these other scales out there that that are important.

  58:07.79

  talknerdy

  Yeah, and I guess I misspoke before when I not that I misspoke because I was talking about Quantum mechanics at the very small and the very big but moving from Newtonian more to relativity right? Just this idea of like and that's kind of what the name implies right? but things are different at relatives.

  58:16.95

  Raghuveer

  Um, and he is in aliette.

  58:24.88

  Raghuveer

  You can? yeah.

  58:26.27

  talknerdy

  Scales I Love It. Oh Gosh. That's really cool. Okay, so we've got these 4 things we've got self-assembly regulatory circuits predictable randomness and scaling and I'm curious for you as a basic researcher. But also who you know is interested in and grapples with and and has done some applied research as Well. How do these four sort of categories. Um influence your thinking as you. As you look into material science into biophysics into translational science in these areas.

  58:55.93

  Raghuveer

  Yeah, yeah, so that's a great question I mean I think one of the things that like in my own research. Really I try to do a lot of is trying to figure out what aspects of things we see things that we see. Can be explained by kind of generic or simpler physical processes. So my my research lab here at the University Of Oregon most of what we do is actually looking at the gut microbiome and these days you know I think everybody's heard of the gut microbiome we carry along this this. Kind of virtual organ of trillions of microbes mostly in our intestines that that do important things and so my lab has been looking at these and looking in in actually the literal sense so we build microscopes that are good at. 3 d imaging and look at zebrafish which are pretty transparent at young ages so we can actually see inside their guts and we've been doing things like actually watching bacterial colonies of different species like grow and bacteria swim around and things like that and you could see kind of a range of different behaviors of.

  01:00:00.22

  talknerdy

  Who are.

  01:00:05.79

  Raghuveer

  Things are aggregated or swimming or stuff like that and there's this you know, wonderfully rich variety. But then you can also ask yourself. Okay, are there any kind of underlying rules that might help us. You know, be able to make predictions and actually say something about why some species take over from other species or some species are unstable or things like that. We do things like okay if we look at you know Clusters of Bacteria is it just random or are there patterns to like what you get in terms of clusters and like we found.. For example that there are kind of patterns that you know you have this kind of process by which small clusters. Seed Larger clusters which seed larger clusters but then the larger you get the more likely it is. You'll be transported out of the gut as you know the gut transports stuff along so there's this kind of equilibrium in a way of all the different kind of sizes of things you get.

  01:00:51.66

  talknerdy

  E.

  01:01:00.89

  Raghuveer

  And certain things like antibiotics can actually perturb that equilibrium and so you could see signatures of that in like these cluster sizes so it definitely influences my work and like you know motivating these kind of questions. Can you find kind of rules of physical structure and stuff like that that that apply to these things. And the answer I should point out isn't always Yes, sometimes there's things where it really does look like it's the details of what the bacteria are doing that are that are key but more often than you might think there are kind of underlying physical processes that help that do help explain stuff.

  01:01:34.37

  talknerdy

  Um, and that's so it's so fundamentally important a from a basic curiosity level right? just trying to make sense of I mean that's what science is and has always been right is just trying to make some amount of sense.

  01:01:47.40

  Raghuveer

  Yeah.

  01:01:51.50

  talknerdy

  Of the observations of of the of the natural world around us but also from ah from an applied perspective I mean there are so many like Health consequences medical Um, ah, potential medical ah strategies that can be taken if we under. So.

  01:01:54.71

  Raghuveer

  Yeah, yeah.

  01:02:06.75

  talknerdy

  And even just the way that like Bacteria layer or Bacteria Clump or Bacteria move I mean we would have you think about people who are septic or people who are dealing with like these intractable infections like how can we utilize physical principles on top of.

  01:02:08.44

  Raghuveer

  Ah, yeah, yeah, yeah.

  01:02:16.67

  Raghuveer

  Yeah, right? Yeah exactly yeah and actually one of the things that motivated our antibiotic work was the fact that there's actually a lot of antibiotic contamination in the environment. So like I think something like 70% of the world's rivers have like.

  01:02:23.25

  talknerdy

  Drug principle. You know I Love that.

  01:02:32.56

  talknerdy

  Mm.

  01:02:36.39

  Raghuveer

  Pretty sizable amounts of antibiotics like found in them mostly from like livestock runoff from those withes. No, it's it's because we're feeding lots and lots of antibiotics to farm animals. Um.

  01:02:38.00

  talknerdy

  E Oh I was going to say is it literally because we're like peeing antibiotics into our toilets. Okay, yeah, yeah, yeah, we forget? That's another scale thing. We forget how many.

  01:02:53.50

  Raghuveer

  That's it is actually that dwarfs. Yeah exactly Oh yeah, there's a beautiful you've probably seen this but a beautiful X Kcd graphic of that. Yeah, yeah, yeah, it's wonderful. Um, so anyway like these concentrations of antibiotics. They're like sublethal that look to the antibiotics or sorry to the bacteria.

  01:02:54.42

  talknerdy

  How many cows there are to every person. Yeah. So Yes God don't you love that cartoon. It's so good.

  01:03:09.67

  talknerdy

  You.

  01:03:11.78

  Raghuveer

  But it turns out people have found that you know low doses of anti antibiotics could still like really perturb the human Cut Microbiome but it's been unclear like why like why do low doses of antibiotics do anything So one of that actually motivated us to look at these low antibiotic doses in Zebrafish and see these sort of structural changes like.

  01:03:16.99

  talknerdy

  E.

  01:03:31.46

  Raghuveer

  What actually happens when you have like weak antibiotics in a microbiome.

  01:03:33.76

  talknerdy

  Oh wow, that's fascinating. Yeah, so so there's also and I think this ah this applies to the scaling principle. Maybe even to a couple others but there's there is this dose response kind of curve that that has large implications. Oh that's it's just fascinating. So.

  01:03:44.20

  Raghuveer

  Yes, oh totally? Yeah, yeah, yeah.

  01:03:51.87

  talknerdy

  Raavir. There's so much more that we could be talking about I could keep you for hours and hours and hours I feel like we did a pretty decent summary of of the 4 physical principles that shape our living world. Um I do close every episode by asking my guest the same 2 big questions. But before we get into that segment I'm just curious if there's anything that we.

  01:03:58.23

  Raghuveer

  I Think so yeah.

  01:04:11.19

  talknerdy

  Didn't touch on or anything we didn't cover that you feel like oh why didn't we talk about that.

  01:04:15.46

  Raghuveer

  Um, I think that's good I I think perhaps the 1 thing that's worth noting is that the whole last part of the book really deals with Dna reading and writing so the technology for like reading genomes and also now with crispr like editing them and that was.

  01:04:29.29

  talknerdy

  Mm.

  01:04:34.83

  Raghuveer

  A lot of fun to write and really made a lot of things chrisp plugggged in my mind and it's not obvious but it turns out a lot of this really hinges on these sort of physical properties of like Dna and other other things and also kind of like we hinted out with predictable. We're endness I think understanding their consequences and what you can and can't do with them. Really also requires an understanding of like what they physically are so yeah I had a lot of fun with that. Oh yes.

  01:04:56.99

  talknerdy

  Right? Oh and that probably has implications for things like um data storage like that's been a huge conversation. Yeah, like how can we use Dna and the coding mechanisms to like store data because we're like running out of space for all of our data. Um, but you need to really understand the physics the actual physics like the the way that these things move and and bind and yes, yeah, we don't think about that we think of it as.

  01:05:19.28

  Raghuveer

  Yeah, and just the Dna is a physical object. It takes up space. It has some stiffness to it. Yeah, like again, it seems kind of obvious but but but yeah, that's not my older son is in in high school you and studied Dna and biology and like. You guys talk about the fact that Dna has a really strong electrical charge. Nope a view that's like central to like so many things. Yeah.

  01:05:39.58

  talknerdy

  Nope yeah I mean I think yeah because people still think coffin of Dna the way that darwin did before Dna was even described that it was like a discrete entity that had ah you know an impact on on different or like the way that mendel talked about it. It wasn't dna yet. It was like.

  01:05:45.29

  Raghuveer

  Yeah, yeah.

  01:05:53.20

  Raghuveer

  Right? Exactly before you do with stuff? Yeah, right? Yeah, it's actual stop here. Yeah, and yeah.

  01:05:57.46

  talknerdy

  Was these like packets of pressures or we didn't know what it was? yeah so yeah, but we know yeah, it's It's actual stuff. It's molecules. It's make stuff and it does stuff. It's got like you said it's charged and it's got things. It wants to stick to and things it wants to repel from and that's really cool.

  01:06:12.86

  Raghuveer

  Yeah, yeah.

  01:06:15.50

  talknerdy

  Okay, okay I'm loving it I'm loving it. Um, ah there was something else that was about to come up in my head. Oh the other thing because I know you're not gonna to your own horn in this way is that guys this book. This is the coolest thing you did all of your own art for the book and and so you did these drawings in these watercolors to like.

  01:06:27.97

  Raghuveer

  Yes, yep.

  01:06:34.24

  talknerdy

  To to visualize a lot of these things. How long have you been doing art.

  01:06:36.46

  Raghuveer

  Oh that's a great question. Well a little bit since high school but it's really more since maybe graduate school something like that. So let's call it 2025 years but

  01:06:50.81

  talknerdy

  Is okay so a long time is it something that you've always used as sort of a tool to communicate your science.

  01:06:56.29

  Raghuveer

  Well actually since since I was a postdoctoral researcher. So for the last twenty years or so yes like I've I've actually liked making sort of schematics and stuff like that and I got kind of more I mean they were generally really awful and I got kind of more serious about this I'm not quite sure why. But I think.

  01:07:00.50

  talknerdy

  We.

  01:07:16.16

  Raghuveer

  When I started as a professor here at the University Of Oregon I think I just just decided to did all to spend what little free time I had doing doing some more drawing well with what free time I had that was not hanging around with my wonderful kids and and trying to do some useful things.

  01:07:28.15

  talknerdy

  E.

  01:07:34.70

  Raghuveer

  In general but trying to spend some time drawing and I got I think a bit more serious about it. But I have like made use of that for like diagrams for actual like scientific papers and I've gotten a couple of Journal covers too from that as well. So also like I mentioned I teach classes especially for non-science major undergraduates.

  01:07:45.42

  talknerdy

  How cool.

  01:07:53.68

  Raghuveer

  And one of those is actually a class called the physics of life which was kind of the the proto version of some of the things in this book and for that you know I also wanted to make things like handouts and stuff for the students I would like make illustrations for that. So yeah, so it's been Ah, it's been an ongoing thing.

  01:08:06.22

  talknerdy

  Ah, cool. Oh gosh I never got anything like that when I was a student I didn't get any cool cool illustrations from my professors that they did themselves I love that except maybe some like crappy like schematics that were made in Ms paint or something back in the head. Ah.

  01:08:13.00

  Raghuveer

  Ah.

  01:08:21.84

  Raghuveer

  Ah, so it's been a lot of fun. Yeah.

  01:08:25.90

  talknerdy

  I Love that. That's so so cool. Okay, so yeah for sure and I mean of course so much of this if we can visualize it and especially in in an in an artistic way I think it really brings it to life because some of these things you can't see or or you know we can kind of see them but not really at the at the level of detail that we want to talk about.

  01:08:36.17

  Raghuveer

  Right? exactly? Yeah yeah.

  01:08:44.68

  talknerdy

  Um, all right? So I'm curious I have these 2 big questions. They're very big picture questions so are are you ready to go there with me. Okay, so I want you to think about the future in whatever context is relevant to you today which you know is um is sort of loaded because we are living in a.

  01:08:52.80

  Raghuveer

  I'm ready good for it.

  01:09:04.85

  talknerdy

  Unprecedented dive but you can think about this in terms of scale everywhere from something very personal something professional something community oriented global even cosmic when you think about the future I Want you to tell me. First what is the thing That's keeping you up the most at night the thing you're most kind of concerned about maybe even pessimistic borderline cynical about what's really really worrisome to you and then you know, let's flip that so that we end on a more positive note. Where are you finding your your hope lately. Where are you finding your optimism.. What are you looking forward to.

  01:09:43.10

  Raghuveer

  There's a wonderful question. So it's good that you start off with a pessimistic one? Yeah yeah, well okay on the pessimistic side. The thing I'm most pessimistic about is actually not covid related.

  01:09:46.52

  talknerdy

  You're right? Yeah I'm always a bad news Verse kind of person. So.

  01:09:59.81

  Raghuveer

  But I feel like we as a society have a hard time dealing with kind of the deluge of information and kind of the deluge of voices out there. So one of the one of the most remarkable books I read in the past year was

  01:10:07.96

  talknerdy

  E.

  01:10:19.19

  Raghuveer

  By Martin Gury it's called the revolt of the public and the crisis of authority in the new millennium. It's kind of a mouthful of a title but he's sort of a political scientist and and kind of crystallizes a lot of things that been kind of going through my mind that you know we used to have this world that wasn't great, but like there were.

  01:10:23.69

  talknerdy

  Okay.

  01:10:38.78

  Raghuveer

  There was ah there were authoritative sources like certain news organizations or governments or things like that that you know for better for worse were kind of treated as authorities and now you know information is dispersed. We have millions of people tweeting which could be great, but. What we seem to have is sort of a a sea of of opposition without construction so to give a quote from that the public opposs but does not propose so almost a sort of nihilism of tearing things down without.

  01:11:03.48

  talknerdy

  Yeah. Right.

  01:11:14.33

  Raghuveer

  Clear path forward for putting things together and a lack of trust then in what used to be the entities that we did trust to put keep things together. So the.

  01:11:20.77

  talknerdy

  Yeah, it's almost like there's been a pendulum swing from like historical sort of um, ah dictatorial rule right? This idea that there there historically was like strong Authoritarian rule in in most nations. Um.

  01:11:29.59

  Raghuveer

  Um, begin. Right.

  01:11:38.47

  talknerdy

  Although there have been you know Periods of enlightenment stuff. There's still usually been a sort of um, ah ah, some sort of acracy you know and and maybe whether it was a plutocracy or whether it was a meritocracy or whatever there was um or an aristocracy. Um.

  01:11:44.62

  Raghuveer

  Right? I think that.

  01:11:54.64

  talknerdy

  There were the people that you trusted and then we sort of started to swing the pendulum to say Okay, it's not about these people being ah anointed by God It's not about them. You know they're special because they've always been special or because they married into a special family. It's that these people know what they're talking about because they're enlightened.

  01:12:11.52

  Raghuveer

  Ah, yeah.

  01:12:11.59

  talknerdy

  Right? Like these people are educated and they have expertise and we've had a long period of people saying Ok, we're going to turn to those who have spent their lives developing expertise about this. And and those are going to be the the voices that we listen to even though they're still a bit of that like oh just because they're the president I Believe everything they say or just because they're a church leader or you know, whatever the case may be or a charismatic speaker. Um, and now yeah, the pendulum is shifting to the point where people are going I don't even believe the people that know things.

  01:12:27.26

  Raghuveer

  Threaten him.

  01:12:39.44

  Raghuveer

  Threat.

  01:12:42.32

  talknerdy

  And I think like all people know all things equally my research on the internet is just as legitimate as your research that you did in a laboratory setting and it's It's super worrisome this like this swing really far out I mean did you watch don't look up like that's what this movie is about.

  01:12:45.59

  Raghuveer

  Me.

  01:12:56.78

  Raghuveer

  Yeah, no you.

  01:13:01.12

  talknerdy

  Um, my God watch it. Oh my God I Just watched it two nights ago and I'm like still having an existential experience after it's bitingly funny. It's very funny but it is also like you feel quite empty at the end of the movie because it's such.

  01:13:09.20

  Raghuveer

  Even. How well rhythm.

  01:13:18.52

  talknerdy

  A satire and such a perfect farce of what we're living in right now taken to an extreme.

  01:13:21.26

  Raghuveer

  Yeah, yeah, so I think yeah, the the question is how do we keep the fact that everybody you know has much more of a voice than they used to but turn that into something constructive.

  01:13:32.93

  talknerdy

  Right? right? And and how do we sort of re invigorate I don't know Reestablish re and maybe not reestablish. Maybe just maybe Re is the wrong prefix to be a prefix to be Using. But. Establish A new way to find trust again? Um, and I think part of it too and I mean not to kind of co-opt this and move in a different direction. But I think part of it is that.

  01:13:52.39

  Raghuveer

  Right? Yeah, yeah, yeah.

  01:14:03.24

  talknerdy

  It has been a natural progression but I think a probably bigger part is that there has been a concerted disinformation effort and campaign by whether they be nations or groups of individuals That's very agenda driven for political purposes. Um, you know like that.

  01:14:15.41

  Raghuveer

  I Think that's true. But I think that I feel like that just accelerated the inevitable. Yeah.

  01:14:23.12

  talknerdy

  You're right I mean it did it. Yeah it it was an exacerbation for sure. Um, but but there's a reason that people glommed onto it right? There's a reason that it was not that hard to do to tip it over.

  01:14:28.72

  Raghuveer

  He had history.

  01:14:34.10

  talknerdy

  Um, so yeah, this is worrisome to me too. This is actually an existential crisis. So so let's let's um, switch gears a little and and see where you're finding your hope because you get up every day you you do your work. You continue to write you continue to um to to hold promise so where is that coming from.

  01:14:48.65

  Raghuveer

  Yeah, well I think 2 things like in ah in a personal sense I do find like what I do both in terms of like my research and like teaching and communication stuff I find it very fulfilling. So I feel like it is a useful thing to be doing and and you know it gets me out of vet in the morning. Um.

  01:15:05.42

  talknerdy

  Yeah, so.

  01:15:08.33

  Raghuveer

  There are many times when I feel like the the difficulties of it have been getting more difficult I mean the administrative Burdens and all kinds of stuff like that. But overall the positives do outweigh the negatives. But oh yeah I mean just the.

  01:15:11.42

  talknerdy

  Um, and the Covid burdens because those exist for sure. Yeah.

  01:15:25.76

  Raghuveer

  Actually 1 of my grad students and I were talking just earlier today like just things are just so much more difficult than they were like two years ago and even if you can't like really articulate. Why just everything is difficult or more difficult than needs to be.

  01:15:31.45

  talknerdy

  Everything.

  01:15:37.32

  talknerdy

  Yeah I was I was I was just saying how like at just at the hospital where I'm where I'm doing my ah psychotherapy training like they're just communications are lost constantly and and like I can't just like so. See the oncologist in the hall or see the psychiatrrist in the hall like so all these things go unsaid and you know because we're all siloed in our little houses and we're doing this stuff separately. Yeah, yeah for sure.

  01:15:53.53

  Raghuveer

  So that's a big. Yeah.

  01:16:00.96

  Raghuveer

  Right? I think we've vastly underestimated how valuable informal communication is like just yeah, hallway conversations and stuff like oh yeah, okay, right? But on the good side. Okay, but yeah like I said personally the positives that way the negatives but also in ah in a more broad sense.

  01:16:11.85

  talknerdy

  Wait This is more bad. Where's the good. Where's the good. Yeah.

  01:16:20.14

  Raghuveer

  You know, ah like um, you know some other things I've been reading in past year or so I read Orwell's George Orwell's down and out in Paris and London about being like really really poor in like the late 1920 s or so.

  01:16:32.33

  talknerdy

  In a time when it would be really hard to be really really poor. Yeah.

  01:16:38.38

  Raghuveer

  And yeah I mean he he literally sells all of his clothes except the ones he's wearing to get money to eat. He goes for like about 60 hours or so without eating at 1 point and I mean just the conditions in in general are just stunningly awful.

  01:16:49.30

  talknerdy

  Mean.

  01:16:56.84

  Raghuveer

  And also another thing I written fast over these you know, really wonderful icelandic sagas which were gorgeous to read but you know everyone in them just spend a huge amount of their time murdering each other and racking vengeance on the the ones who murdered the the ones that they love the time they're not murdering people they're writing poetry Anyway, um. Yeah, a lot of these things really do highlight to me at least that for like we've figured out a lot of we We know how I'm sorry how to how do I put this life is much better than it used to be. We've We've really figured out I mean.

  01:17:30.78

  talknerdy

  Oh hell yes.

  01:17:35.52

  Raghuveer

  I think people'll often lose sight of this even you know things like basic sustenance crime on all these sort of measures life is just vastly better and it's not better for absolutely everybody on the planet but over what like it's better for a far higher fracture of the planet than it than it used to be and that. Trend is going. You know ever upwards the fraction of people who live in desperate poverty for example has been. You know, just radically declining for for many decades so you know we figured out how to get a lot more food out of you know, an acre of of land. We figured out all kinds of things. So 1 thing that often just kind of strikes me is.

  01:18:06.50

  talknerdy

  E.

  01:18:13.40

  talknerdy

  He.

  01:18:13.57

  Raghuveer

  Basically we've won we we know how to have a you know, not perfect, but pretty good life. We just need like we have. We've invented all the tools. So now we just need to kind of implement them and you know that implementing is still a big step. But.

  01:18:24.19

  talknerdy

  Right? I think yeah.

  01:18:30.93

  Raghuveer

  You know a hundred years ago we couldn't even make that statement that we have the tools there I think.

  01:18:34.44

  talknerdy

  It's true I mean now. So so many problems that are facing us like big existential problems like climate change are are problems of political Will they're not problems of technology necessarily um because we at least have a good starting point. But you're right like across so many.

  01:18:40.78

  Raghuveer

  Right.

  01:18:51.76

  talknerdy

  Levels I As a as a Latina woman would not want to live any time except now you know I don't want to go back in the past like and and even even now it's not great and I'm hoping for an even better future. But hell no I'm not going in the past and I feel like I know a lot of people who could say the same thing. Um.

  01:18:55.18

  Raghuveer

  Exactly? Yeah, yeah, right? exactly. Exactly you? Yeah, Definitely definitely Oh totally? Yes, Yes, yeah, yeah, yeah.

  01:19:08.57

  talknerdy

  Ah, anybody who's lgbtqi Plus anybody who is you know a person of color a woman anything like that. Um, and then you add to that you're right these these basic metrics like infant mortality like hunger like you know, ah life expectancy and all of that and they've only gone up and I think one of the um. Sort of important things to remember and and you're touching on this but it's something I've been struggling or thinking about a lot lately because I've been I've just been reading a lot is like I don't think people are reading as much as they used to and so much good stuff is in those books you Guys. We don't have to reinvent it. We don't have to.

  01:19:38.96

  Raghuveer

  Um, oh yeah, yeah, yeah, yes.

  01:19:46.44

  talknerdy

  You know like it's there. These ideas have been grappled with for Millennia and like there's so many good ideas in these books. Why aren't we reading them? ah.

  01:19:49.49

  Raghuveer

  Yeah I I completely agree.

  01:19:58.69

  talknerdy

  Gosh this has been this has been exhilarating. Um, thank you so much for like being flexible in your in your scheduling to meet with me during this weird kind of time. Oh good, good good and so everybody the book is so simple a beginning how 4 physical principles shape our living world. Um.

  01:20:04.45

  Raghuveer

  Oh thank you. This has been a lot of fun.

  01:20:15.60

  talknerdy

  Go out and get it. You can pre-order it right now and it'll be available on February Eighth very very soon. So yeah, pre-order it now so that you can get it the day that it that it comes out. Raghuveer, thank you so much for taking time with me today and everybody listening.

  01:20:18.90

  Raghuveer

  February Eighth yep

  01:20:28.43

  Raghuveer

  Thanks so much. This is a wonderful wonderful conversation I had a lot of fun.

  01:20:34.73

  talknerdy

  Yeah, me too and everyone listening. Thank you for coming back week after week I'm really looking forward to the next time we all get together to talk nerdy.