Finding your Science Communication Identity : Dr. Pallav Kosuri

In this episode, I interviewed Dr. Pallav Kosuri. Per Pallav’s website, he studied physics in college at KTH in Stockholm, Sweden (where he’s from). As a PhD student in the lab of Julio Fernandez at Columbia University, he studied the mechanics of protein folding and discovered that we can modulate this process to alter the elasticity of muscles. He then moved to Harvard University as a postdoc in the lab of Xiaowei Zhuang, where he used DNA to invent and build nanosensors that make it possible to see molecular movements. Since starting his lab at the Salk Institute in 2021, he has been excited about building a diverse and thriving research community, while training future leaders in biophysics. When he’s not in the lab, you can find him rock climbing, skiing, or learning to surf.

Transcription

Transcribed by Reid Bowman (they/them)

Dr. Pallav Kosuri (PK): I still have sort of the same motivation that I’ve had since childhood of like figuring things out and tinkering with things and learning by breaking stuff and, but…but not living stuff and think that’s maybe what’s made me, um dive more into physics rather than biology. When I went to college I majored in physics in Sweden and I always saw myself as sort of, like, “yeah, I’ll work with lasers or with particle physics or something else that is like fairly esoteric but very fundamental to how the world works” and that was my intro into science in general. I enjoyed physics because…not only because of these, like, mind games that kind of place on you the more learn the more you’re, like, questioning reality, but I also liked it because I didn’t have to memorize much. Quite honestly, I was pretty lazy as a kid, like, you know, I probably would have gone into other fields or learned about other things like biology or chemistry, but there were things you had to learn before you could do something interesting or you know– Even the things that we were told, or that I was told in school, in chemistry that was like, I was told was important was to know the names of the elements and their order and identify reactions from like a, basically a bunch of stereotype reactions that I’ve learned that I’ve learned myself, right? But in physics it was different. It was like if you understand how equations work and how to manipulate them, then you can go from one concept, like some some fundamental assumptions, and just like derive your way through all of modern physics. And that was so satisfying, like I could show up to an exam and I’d be like, “Yeah, I forgot all these equations, but I could just derive them on this one.”

Interviewer (I): Yeah. Is that what we’re seeing on your whiteboard behind you?

PK: These are the Next Generation. Yeah. Yeah. These are questions that your kids will hopefully [laugh] – No, we’re just tinkering. But yeah, that was what drew me into physics. Actually…[pause] Nothing secret on the board, I think it’s fine. We use thi– This is like our brain, you know like, we just have discussions and then we draw things on board and them we take photos of it and we post it on our internal Slack channel and, um, it will refresh it every couple of days. So,

I: Yeah

PK: –usually like this is what’s happening in brain right now – you a projection of it, like, behind me.

I: [laughing]

PK: Yeah, Gaussians [referring to the board behind him]. But yeah, my journey to science is initially through physics and and through, like, lack of memorization and just like fascination with nature in general, I guess. But then over time, I realized that the physics that was done 100 years ago is now a part of our life, like [incomprehensible] waves and MRI scans and all this stuff, right? But not that much of the foundational, like, sort of fundamental physics that is being done now has any application in the near future. There’s some exceptions, like quantum computers are probably going to be useful fairly soon, and they’re definitely areas of physics that are directly relevant, but I felt as a recently graduated college student that, you know, I this idea that I was like, “Oh physics isn’t what I thought it was” or “what it to be” or something, which is, like, weird to be nostalgic when you’re 20 [laugh], but then I learned about what was happening in biotech in biology and I was like, “This is it,” like, “This is where things are happening. This is where people come up with ideas like…in the shower or like over coffee conversations or…yeah, like, you– back of an envelope, like, sketch,” right? And then the next couple of days, we set an experiment in the lab and like, discover something fundamental about nature or that we can make you [incomprehensible] out DNA. Like, those…like the speed from this…the time from conception of an idea to realization, combined with the amount of fundamental advances that we made in this field over the last couple of years is unmatched. I haven’t seen it. The only thing that comes close is…is computer science and machine learning, which you also see–

I: Right.

PK: –like right…right now like things– People have ideas and they impact the world, you know? Within few weeks, you know? That– Which is wild, right? So maybe if I went into it, like, if I had the thoughts today, I might have gone into machine learning or some form of AI research, but back then it was like, biology was the the thing and I still think it is.

Second Interviewer (SI): Yeah, um, you mentioned graduating college at 20! Um, how was that? Like, I’m about to turn 20 in a few days, like it’s crazy to imagine, like, being graduated from college at that age, you know? Like, I: You graduated college at 20?

PK: We a different system in Sweden. I…

I: Oh [laugh]

PK: It’s um…it’s not that different. It was still important to have…it was important to have your program, in my case, but I did graduate a bit earlier, I started school earlier and… but, uh…I will say, though, and no shade to Sweden – they’re awesome – but I do think you have it harder. Like, the workload that you have as college students from the University I’ve attended here in the US, um, seems to overall be a little bit higher than what we have in Sweden. The material is the same. We learned the same things, like the courses have the same content, but the…like the homeworks are just more.

SI: Yeah

PK: Like, it’s harder to cram like, you know…to cram four years into three years here, then it was, for instance, in Sweden.

SI: Yeah, so, uh, yeah, I guess, taking a bit of a step back. It’s really relieving to hear you say that chemistry was a tedious subject for you

I: [laugh]

SI: –because, I mean, there’s something I can definitely relate to. Um, but yeah…Pivoting a little bit. Uh, so you said, like, University settings are completely different here and in Sweden and now I know you at the Salk Institute, what exactly is the Salk Institute and how would you say it differs from a university setting?

PK: Yeah! I I learned about this fairly late in my career too. Salk has…generally not kept a very high profile and it’s primarily been a biological research institute, although now we’re branching out and we do more interdisciplinary research. It was founded by Jonas Salk. Jonas Salk is mostly famous because he invented the, uh… SI: Polio!

PK: –the first effective and safe vaccine for Polio. And so through his vaccine, and the developments of it later, we basically don’t have polio as a worldwide plague anymore. Before his vaccine, there were 15 million people suffering from polio and it was…it was really debilitating for tons of people. And at the time, you know, there no cure, there no useful treatment, and there was no vaccine, right? And so, by doing that, he had, I would say, single-handedly an impact on mankind that is, you know, hard to match in any other way. Like, this was really profound. The amount of lives that he saved, right? It’s hard also, because it’s like…it’s less tangible because it’s not like he cured people. He just…made it so that people didn’t die in the future, right?

SI: Right.

PK: It’s kind of like, um…stopping climate change. Like, you’re not saving people now, but you’re– You know that you’re reducing the number people who will suffer and die in the future. Even though one those two ways, you know, like…You know curing people versus preventing people to get sick don’t always get same amount of attention and glory. For instance, Jonas never won a Nobel Prize, even though I would say it’s…That would been an one to decide [laugh], but that being said, what he did for humanity was really remarkable and a lot of people saw that and and recognized the potential, not just for his impact of the work he had done, but the he did work and what he chose work on, right? Like, this a guy who knows how to benefit society more than possibly most of the established scientific community. So several foundations and donors supported him in building this institute and it opened in the 60s. And it was built here in San Diego. Uh, because this land that we’re on now was donated by the city of San Diego. It was originally intended to be part of the UC San Diego, but the University was under construction back then. And now we do have an affiliation with UC San Diego, but we are an independent research institution. And, on the ground, what makes it different for the scientists here is that– I’m a professor, you know. I run a research lab. We have about 13 people working in the lab right now. I’ve been here for three years and I can spend all my time doing science. I do not teach. I can teach if I want to and did actually last year, mostly because I enjoyed teaching and because you get to meet students and students are awesome as you know. But we don’t have the teaching load that people have if they’re a professor in the university, typically. There are some exceptions. We do have, like, a minimal teaching load. I think it’s, like, three hours a year, or something, but we could just give guest lectures and that’s fine. But from my point of view, it was really the utopia in of focusing on the science, being surrounded by a small but brilliant community, interdisciplinary scientists and all being driven by this, like, Jonah Salk vision of “how can we make the…how can we do the most good for humanity and and push the boundaries in a way that people don’t do elsewhere,” right?

I: Yeah cool, but don’t forget to mention that you’re also in San Diego. So I’m from LA – I’m a West Coast boy, don’t forget to mention the weather and the 70 degree weather– like, the temperature there’s awesome all the time.

PK: [laughs]

I: Don’t forget. [laughs]

PK: I know! I know! I know Jonas Salk…he was, like, shopping around for place to build this institute. That might have played a factor. I know for a fact, but like…I mean, like, you come here, he was in Pittsburgh before and he, like, looked out over the ocean, you know. Saw the sunset. I mean it’s hard not to fall in love with this place. It’s uh…it’s quite inspiring and we have this channel of water that runs along the courtyard. So the Institute itself was designed by Louis Kohn[spelling?] who is a phenomenal architect and…He worked with Jonas Salk, and they, together, designed basically every aspect of this institute to help scientists and the science to be more efficient and just work better. But then a lot of artistic features too. They are symbolic in nature. So one is, we call the “River of Life.” There’s, like, a river that runs along the institute and it goes past all the labs and then falls out into an infinity pool into what looks like the ocean all the way – we’re a bit offset from the ocean – and it’s supposed to symbolize how we generate knowledge here and the purpose is for knowledge to flow out into the world. And I think that’s very poetic. I see that every morning and it inspires me to work, so…

I: Cool! Well, hopefully I can afford San Diego one day,

PK: [laughs]

I: –but I do have a question for you.

PK: Well, I live in a lab, so you don’t need much money.

I: [laughs] Yeah,maybe I can crash in one of your Labs. But I was wondering, can you take off your scientist cap off for a second? So on a podcast I listened to, you mentioned having a rather strict father from India and a mother from Sweden who is probably the, quote-unquote, “chill parent,” right? So that resonated with me so deeply because I kind of had that experience too, right? My step-dad is Mexican-Native American. My stepmom is Filipino. So whenever she was mad she, you know, would yell at me in Tagalog when I did something wrong, right? So tell about your upbringings. How have your upbringings influenced today, you seem you seem pretty chill. You seem like a West Coast type of person.

PK: Oh, [laughs] it’s… I think what makes it West Coast is that…You know the duck analogy?

I: [stammering] No?

SI: Duck analogy?

I: Should I? [laughs] Should I know the duck?

PK: I mean, it’s like a Stanford thing, I don’t know. Like, I was told this by my friends at Stanford, but basically like…People on the west coast, especially in the academic world, they are like, so chill on surface. If you look at a duck it’s like, serene, right? The duck is just, like, chilling. But if you look at the water like, it’s paddling like crazy!

I: [laughs] Yeah.

PK: That’s– I… I mean…Now having been on the East Coast for many years and I just moved here three years ago. I resonate with that. Like I definitely think that it’s… there’s a of like…On the East Coast, everyone projects their stress like outward and we’re like, “Oh man, I will here until midnight last night,” and like…here we don’t talk about it and we don’t show it but like, we work just as hard like, we’re still stressed, so don’t get me wrong. The way I benefited from it, though, is that through this…like maybe I internalized the duck analogy too. Like I reframe, you know, like I reframed this stress as excitement it’s true. It’s true to some degree. Like if you find something you’re really passionate about, like science or whatever vocation it is that you have in life. If you really enjoy it, then it doesn’t always feel like a burden, you know? And for me, I have to say, it almost never feels like a burden. I am so grateful to be here, to be able to work with these fantastic people that I’m surrounded by and my lab members are absolutely brilliant. Like it’s such a privilege to be here and they’re busting their, you know…

I: You can say it. You can say it.

PK: –butts. Yeah! And like…I just…you know, I can’t give less than 100% to support the people around me and the amazing research they’re doing. So that way like, yeah, we do feel stressed, but we probably enjoy the stress more than I did, at least, on the East Coast.

SI: So…What I’m hearing is you’re just you just think about all of us East Coasters are just a bunch of complainers.

PK: Uhh…Not just a bunch of complainers [laughs], but I was saying, you know like, when I was in New York, like…if someone was having a bad day, I would know, you know? Am I wrong?

SI: [laughs] That makes sense. That’s very fair. It’s also New York.

PK: [laughs] Yeah, maybe that’s a New York thing, I don’t know. But it also wasn’t much different to be honest. I feel like if you go south you get a little bit more politeness, more like West Coast and chill attitude also, so you might be like…

SI: North Carolina is pretty good!

PK: Yeah, that’s what I was gonna say! I haven’t spent enough time there, but I would love to.

SI: Yeah, so I guess, putting your researcher’s cap back on, what does a day in your life look like? What would– Talk about like a bit about what you’re researching now.

PK: Yeah, I was…I told you before, I didn’t used to know what a professor did and I still don’t

JP + SI: [laughs]

PK: Like, there is no…The one thing I would say is, and it’s so cliche, but like there is no typical day. There really is no typical day. If there are two days that are similar, then I really start to be like, “Is something wrong,” like, “What’s going on?” [laughs]

I: “I should move back to the east coast?” [laughs]

PK: “I didn’t have like a crazy podcast with some awesome undergrads,” or, you know, like…

SI: You flatter us too much!

PK: You guys are great! I can tell you what we’re doing scientifically, I can’t really tell you what I’m doing like…in my life because they’re all these different meetings and you talk to people of sorts and yeah. Scientifically, we’re developing…Largely, we’re developing new methods, new ways of seeing nature and new ways of manipulating nature. And so my lab sort of has two main sides, you know, main directions, in a way. One is to do similar things to what you saw maybe on the YouTube video with Mark Rober, which is we build the structures, devices and sensors using DNA as a building material. So we’re sort of repurposing DNA, the molecule DNA, into a structural tool and a diagnostic tool. So it’s something that we can, you know, shape into our our hearts’ desires. And that has a lot of applications, right? You can think of this like, you know, you can build little scaffolds for sensors, for chips, for potentially artificial organs or devices that can go into your body – or maybe work outside of your body – and

and that’s one side of the lab, right? And the other side of the lab is more focused on imaging and studying the architecture of organs. And the crazy thing is that it’s actually the same technology, but just slightly repurposed. So in terms the DNA origami work, we use DNA to build physical structures, but in the imaging side, we are repurposing DNA to, uh, transmit information to us in new ways. So you can see, for instance, which genes are expressed in different cells in a tissue or we’re working on methods that allow us to use the DNA sort of as a messenger to tell us other properties of tissues and cells. So that’s a bit– It would take me a little bit longer to explain exactly how we do that, but just fundamentally it comes from understanding that DNA serves a lot of purposes in nature and, uh, we can do more. Like, we can repurpose the DNA because we understand it so well now. That we can have it, you know, encode different kinds of informations and we can outfit it with different probes and labels that allow us to, you know, image it in complex patterns and, yeah, repurpose it for information technologies.

I: Yeah–

SI: DNA origami…What a concept.

PK: Well, I think just the name “DNA origami,” it’s, like, so thought-provoking, right?

SI: Yeah!

PK: So I’m lucky to know the inventor of both the term DNA Origami and the professor who published the first paper using DNA Origami…and his name– Paul Rothman is his name he was…At the time he was a professor at CalTech…Might still hold that position, actually. And this paper, like…it was a single-author paper. He published it on his own. He was kind of working on this for probably for years behind the scenes and then he both coined this term and, that’s the title of the paper, “DNA Origami,” right? And then he showed that you could use DNA to build all these different structures. And for me, I was a student at the time when I saw this paper and I was just so inspired by just what that evokes, like, you can fold DNA into structures, like, they’re going to be so many things you can do with it, right? So I think – and this is something that I take away from this um, “episode” is that it’s not just what you do. It’s also how you communicate. Because by calling it “DNA Origami” and not like “DNA Self-Assembly Nanotechnology,” he essentially inspired a whole generation of new scientists and students to go into this field with this, like, creative visionary attitude that we would not have had, had it not been for that term. So that’s…I think that goes to show you how powerful it is, the way you portray and communicate your work. Not just–

SI: Yeah! Absolutely. And going back to some the stuff you’re talking about with like tissue engineering and stuff – as a biomedical engineering major, it is my job to be concerned about those kinds things and I was I was really, really intrigued on like DNA origami in general and just…how it works and the future implications. Like, I think I’m not sure if you mentioned in the Mark Rober video but, like, gene therapy, like creating a vector using DNA – how would that work? How would tissue engineering work? Like, could you just go into more detail about that?

PK: Like, you mean if you were to use DNA as a vehicle to deliver different therapeutic agents? That’s what you mean?

SI: Yeah.

PK: I see it as sort a natural evolution of the current technology. I don’t know if the future will be DNA origami or if it will be some alternative technology. But if you think conceptually about how we deliver drugs to specific locations in our bodies, typically, we hope that the drug will get there. We chemically engineered it in such a way that will be transported, and then more recently, you know, a lot of our treatments and drugs have become more…they’re less…Fewer of them are small molecules; more of them are biological, more complex molecules. In Pharma, we call it biologics. It could be proteins. It be DNA. It could RNA. And an example of this is the RNA vaccines. Right? Like we’re all familiar with the RNA vaccines. It was so funny to see, sorry to use this term to refer to covid, but I’m specifically referring to the vaccine development. It was funny to see this…we had been a bunch of people. I was new to the field, right? But DNA origami, but there’s many people who were like, the future of RNA delivery for instance is like building these like complex microscopic robots that would like going to your body and swim to the tissue of choice and identify the right cell and like do a handshake and like release its material and then the technology that won - the technology that like ended up in our bodies - was literally a blob of fat. They’re called lipid nanoparticles, but it’s a drop of fat like, that’s all it is. Right? And that’s what we inject. We emulsify the RNA in these droplets and they just sit there, and because it’s a lipid particle, it doesn’t dissolve in our bloodstream or in our tissue or in the water, but it stays as a droplet and then you can encapsulate the RNA inside of it, right? And then that’s what ended up like, you know, vaccinating all these people from covid and it was the stupidest technology, like, conceptually, but practically it ended up being the most useful. So in the evolution of things like now in retrospect it kind makes sense. Like why would you start with a super complex nanorobot when you could just have a blob of fat? Like, that actually seems easier, you know if that works, but I do think in the future now that we’ve opened the door for these like delivery vehicles. They have to become more complex as demands increase and diseases get more complex and the treatments get more complex. And as we want to have fewer side effects and more specific treatment. We have to make the vehicles themselves more complex. And one thing that DNA origami has over many other design technologies is that we can already build custom 3D shapes. Like, we– you know, we prototype a lot of things that we do in the lab and we 3D print them and we can make these like complex three-dimensional [incomprehensible] [audio cuts out].

–we can already build and so if you think about these blobs fat progressively getting [audio cuts out].

[Pause]

I: [partial audio] is how you talked about science communication, right? So one thing I need to really acknowledge is how good you are at communicating your sign. So you just did like a master class right there, right? And again, I listen to this podcast where you’re about how humans basically have built ways to and function examples being like how humans build buildings, elevators, and escalators or like, you know, with the blueprint example in Mark Rober video. So, can you tell me what is your thought process when you’re thinking about taking a complex concept like DNA origami and putting it in language that everyone can understand? Because it seems so like easy for you, but there’s gonna be like a method to madness, right like?

SI: Oh and it’s like one of the most important questions for [incomprehensible] as well, like this is one our major motivations in general and like not not to gas you up too much but a wonderful job.

PK: [laughs] Thank you. Thank you. Yeah. [Pause]

I: Maybe that’s the million dollar question.

PK: It’s not the million– no, it’s…it’s a very important question. It’s a hard question. I’d say it’s a hard question. I mean, to be perfectly truthful, I don’t think it’s 100% conscious, right? So, I can think about how I present concepts and ideas and, especially since becoming a professor, I feel like I’ve had the opportunity to explore different ways of communicating and I find myself thinking and reflecting a lot on how I describe things and try to refine it. So there’s definitely a method there. But then I also…I just think I’m always talked a lot. So that helps, but…Oh another thing is like I don’t have any social anxiety, essentially. That helps also and I think that stems from when I was a kid, you know, we both had overbearing, Asian parents. So I was forced to do a bunch of stuff like play instruments and sing in choirs and I’m very thankful in retrospect, but at the time it was harrowing, you know. I have to go to all these concerts and perform for all these people and I never wanted to be on stage, but it did train me, right? Like, so I figured out ways to to feel comfortable on stage in front of people and that has, I mean, that has really paid off enormously now like actually being in a lot of public situations. So I think just like, remaining calm and being yourself in these situations helps a lot. Like if you put on this persona that like “Oh, I’m a professor” or “I’m a teacher” or “I’m a mentor” or whatever that means right? “I’m an expert.” That can come with good consequences like, for instance, you hold yourself to a higher standard, right? But it could also come with negative consequences such as: you become more formal and you speak in a language that is more alienating and is more like, field specific which isn’t really helpful when it comes to communicating what you do. So maybe the first thing is just…stay grounded. Like, you’re having a conversation, right? Don’t think of it as a lecture because lectures are boring! Like that is almost synonymous at this point right? Like “Oh, stop giving me a lecture.” That’s an insult. [laughs] I think should say something to people who give lectures like, maybe maybe they [incomprehensible]

I: I know! Homie’s getting thrown around over there.

PK: So I hope you find peace, right? Yeah. So yeah, so I would say…are y’all good?

SI: Yeah, we’re good.

PK: If you need to reposition, don’t worry about us - we’re fine. Yeah, um, so yeah, so I think just like taking it down to conversational level realizing that that’s all science is at the of the day right this conversation. We either have conversations with our fellow scientists or have conversations with people that are not scientists, but they’re still just conversations. They don’t need to be lectures. And then the second thing I would say is, you know, be harsh to yourself like, listen to yourself. Like it’s cringy to see yourself on screen. It’s cringy to hear yourself. Like I will watch this in future and I will be like, “Oh no!” You know? And just like, get over yourself. You’re not going to get better if you don’t push through that and then give yourself the harsh feedback that you need, right? So one thing I’ve thought about a lot is like, I used to wave around with my hands a lot, like a very visual speaker. And then I said “Maybe I should figure out how to think more about every word that I use and how to use it.” But in general, they’re just a few things that are fairly simple tricks. The more specialized you get in a field, the more familiar you are with this specific jargon of that field and that is not great. Fight against that. You have to remember what it felt like– See yourself from the point of view of someone who’s not in the field and say, like, “Oh, is there any word in that sentence that I would recognize immediately?” and if the answer is yes, then you should be explaining that concept and maybe you don’t even need to use that word.

SI: Yeah! So Dr. Kosuri, I know you’re an engineer by training and I think you’re moving into RNA pol 2 dynamics and like transcription now? And so I know JP is studying, you know, 3D chromatin structure and chromatin looping. Um, So, um, I know this is his question, I kind of stole it. Sorry JP. But how do you think chromatin you know, and its different states is affecting the dynamics of RNA pol 2.

I: So this is about to be a psycom workshop. We’re putting you the spot right now.

PK: Yeah, So I actually haven’t studied Pol 2 to yet. We studied [unclear] polymerases like RNA polymerase bacteria. They only have one at least so RNA polymerase in E coli, which is the organism that we get our enzymes from. They have like one basic enzyme component and then it gets paired with different subunits and depending on the complex structure, they have different properties. In humans we have separate genes and coding for different versions of RNA polymerase and pol two is the one. It’s the main character, if you will, and yeah. So the question is that chromatin structure affects folded dynamics? Yeah, so I mean… that is that is an excellent question. That is an excellent question. There are many aspects to how I would start to investigate it. I mean, a lot of it is known already. We know that just structurally and mechanically, chromatin or condensed… chromatin is essentially…this one of those examples, right? Like you would hope that people would know what chromatin is, but this is actually just like condensed DNA. So just like you can take any other material and either have it like unraveled or condensed, chromatin is sort of a catch-all term for any way that the DNA is structured in a more compact way, right? So you could be either wrapped around these little spools that call nucleosomes or it be sort of aggregated together with proteins that basically bind it together. It can be sequestered against the wall of the nucleus. There’s like a protein shell of the nucleus and a lot of the chromatin just like DNA clumped and stuck to the wall. And in all of those cases. it’s more like…it’s it’s mechanically more difficult for RNA polymerase to access that DNA. So there’s a purely mechanical barrier, right, that there’s nothing to do with the chemistry or with regulation that comes from interactions with other proteins and so forth. It’s like this little thing is a little choo-choo train that goes on the DNA and it transcribes it into RNA and it encounters like a roadblock, right? And the short part of that story is like we don’t fully understand how the mechanics of this roadblock impacts RNA polymerase and the reason why we don’t understand that very well is because it’s very difficult to see– to measure the effect of mechanical barriers on RNA polymerase. It’s very difficult to reconstitute some of these situations that we see in cells and in a lab, in a setting where we can actually see individual RNA polymerase enzymes move. Now that being said, there is there’s a lot of people who have made advances in this field and one of the methods that have been super useful for understanding this is “optical tweezers.” So you basically like use the…Optical tweezers is a way you can like capture little plastic beads in a laser beam, and then you can move them like very precisely like a tweezer and so what you do is you can like hold the DNA on one bead and you’re going to hold the RNA polymerase on another bead and you can essentially watch the RNA like slowly pull the bead towards the side that it’s walking, right? And if you make the DNA with roadblocks on it, then you can actually study how exactly the RNA polymerase interacts with it. And from my understanding…I’m sure if this has been done with human versions of the enzyme, but definitely for bacterial versions of the enzyme, which could be like a model way of studying humans, assuming that they are similar. There’s a scientist at Stanford who, at the time, was at Berkeley. Her name is [redacted]. She did some of the pioneering studies using this technology about 10 years ago or so, but these experiments are extremely difficult to do. You essentially have to attach like a single enzyme to a plastic bead and a single piece of DNA to another plastic bead and then assemble the histone or the nucleosome on there and then like trap these things in laser beams and then like watch them come together and hopefully, the stars align and everything goes well. She managed to do this and I admire her greatly and…

SI: It sounds like my worst nightmare.

PK: [laughs] It’s nothing that I would wish on my worst enemies, right? Like it’s a very difficult experiment and it was groundbreaking, but it’s not something that we can use to study, you know in general how these systems work. And that’s why there’s so much unstudied when it comes to the interactions between polymerase or other enzymes and DNA and chromatin. Yeah.

I: I wish you my teacher in college because I feel like if I heard you explain it that way, I would have learned things a lot faster.

SI: I would have been a lot more interested too.

I: Yeah, seriously. I think you should start taking up teaching again, Doctor Kosuri.

PK: Oh no! [laugh] Yeah. Sure. I would love to. I mean, I think what’s going to happen in the field is that people will enjoy being taught by certain teachers more than others or people will learn better from teachers. I don’t know if I’m the best, but I certainly try.

SI: Oh you’re up there for sure.

PK: [laughs] Thank you. Thank you but, um, this is possible right? But thanks to people like you who make podcasts like, you know, we can learn from anyone, right? As long as they’re available online. And so I would encourage all of my colleagues and people who enjoy teaching and especially people who are happy doing this to do this as much as possible because the more material we have out there, the more everyone can learn right?

I: Yeah, definitely. So you brought them up early, but I kind of want to bring him up again. Mark Rober. Him and his science communication efforts are amazing as well. So, how was working with him? I’m sure you guys got along well because you’re engineers, but…

PK: [laugh] We were surprised, yeah! We just clicked, like I can tell you. Do you want to hear a little “behind the stories” secret? So you know like, when you see…like you watch a video or a TV show or something and like, you know the host walks up to a door and knocks on it and then the other person opens and they’re like, “Hi! I’m so-and-so” and they introduce each other? I always thought this was the stupidest thing ever, like clearly they know each other they planned this out. They’ve gone over it, you know, a million times. It’s like this is probably the 10th take, right? No! Like Mark didn’t do that. And I mean, he told me. He was like “I’m a terrible actor. I could never do this twice. Like, it would not– like, nobody will believe it.” So I didn’t actually hear from him the first time, but basically, his team was like, “Oh, yeah, then Mark Rober is just gonna like, show up at your door and then we go from there.” And I was like, “What!?” I’ve never met this person in my life. I’ve seen videos there. He’s definitely a bigger-than-life figure. I hadn’t rehearsed anything, right? And they told me they were like, “oh, yeah, like at some like 2 p.m. tomorrow. He’s just gonna knock on your door and it’s gonna be a camera team.” So that’s a true story of like when you see us like shake hands and like… that was the first time I met him. Nothing was scripted. It was absolutely terrifying. As I said, I don’t get social anxiety, but I was pretty nervous. But yeah, he was super down earth. Like once we got past the initial, you know, my stage fright, he was super chill and I found that even though he doesn’t have any specific background knowledge in DNA nanotechnology like, it was just super quick. He picked it up right away. He asked all the right questions. I just felt like it was so much fun to talk to him because he would like…Every time I said something he would be this kind of like “Yes, and?” person like people build on it…Was like “what else could you do with that? Could you do this? Could you do this?” And I was like, “Yeah! Yeah, we should do this!” like, “we should play this!” and like, “Oh, let’s do a follow-up video! Let’s, you know, make actual Nerf guns that can shoot DNA into cells. Let’s do it!” That was super fun and we had planned– we had kind of like set it up. So I talked to my students before, like you saw them in the video, [student] and…We had planned to like, “Maybe we’ll do like a prep when he’s here. Like maybe we’ll actually build the Nerf blasters like in the lab when he’s here.” It would have been pretty cool. They can film the whole thing instead of just showing the product, right? And then he like showed up and he was so excited about all of this that I was like “Wait, Mark, do you want to do this?” and he was like, “Well, can I?” I said, “Well, what are they gonna do?”

I: That’s awesome…

PK: You know, we’ll make it safe, so my students taught Mark Rober how to pipette and he did great,

SI: That is awesome. Yeah, that’s gotta be like their biggest flex when they get older like “I taught Mark Rober how to pipette.”

PK: Right! And like, you know, when he got something wrong she was like “uh-uh!” I think you see one of those things in the video too. Like [student] like, you know, Mark Rober hands his tube to [student]–

SI: He wasn’t wearing gloves?

PK: Yeah, “did you label this?” and he was like, “so sorry.”

SI: For all the listeners out there, check out the video. It’s a really fun watch. Yes speaking of the microbial video, that’s where I first heard about you and was really intrigued by your work with DNA origami. That’s where I actually learned the term also, and using the blueprint of DNA and building the house using that blueprint. Can you talk a little bit more about what this is, what this analogy is and what it means just moving forward in science, like whether it be something like gene therapy treatments?

PK: Yeah. Yeah, I mean, I think the most important fact is that we can already build all sorts of different things using DNA. It’s not a science fiction thing anymore. It sounds like science fiction to people who aren’t in the field, but for us who are in the field, this is what we do. It’s not just my lab, like there are lots of labs around the world that use this technology and it’s basically limited by our creativity and the work that we put into making things into real applications. So for anyone out there who is curious about this, this field is just like ready to go. Like we’re kind of at an inflection point in a way where we have all the tools we need to make complex structures, but we haven’t seen them translate out to reality yet. Like they haven’t impacted people’s lives in the way that they could. And I think it’s the same thing with gene therapy. That’s not that’s not what we’re doing. What we do might be helpful to gene therapy but if you think about technologies like Crispr for instance, which you could use to edit genes. It sounded like science fiction, but then someone made it work, right, and now they just the other week…a couple weeks ago…the first crispr Gene editing therapy was approved for clinical use in Great Britain. And so this is like the beginning, you know. Over the next couple of years, you will see tons of real-world applications of using crispr in actual clinics and to cure people of terrible diseases. We’ve already seen it play a huge role in the research and development of new products. But as consumers, you don’t really see a lot of that. Like, you don’t notice that a lot of the things around you are built like teen edited technology, but it does already play a role and I think that’s like DNA origami and DNA nanotechnology is right there too. It’s taking a bit longer to grow it out to this potential like, you know Crispers, you know, conceptually it’s simple – you have one gene, you make one edit, one location. But for DNA origami, it’s slightly more complex, like we’re building three-dimensional structures and we have to varify that they assemble correctly and that they have the geometry that we want and that they are stable and that they’re mechanically rigid and so forth. But we are at that point where these things work and they work every day in our lab. So yeah, it’s up to you guys, really.

SI: I think that’s so cool.

PK: The analogy that I like is silicon, like transistors in the 60s. There were a bunch of people like toying around with transistors in electronics labs, which was, as you know, a private research lab like the Salk Institute for electronics and they were just like these weirdos fidgeting with strange electrical properties. And someone was like, “Well you can make this into like…this thing can carry out a logical operation” and that’s where it began. Someone realized that these silicon devices, you know these transistors. If you connect them in a certain way they can execute logical protocols. Like they can act in ways that follow a set of mathematical rules that we can actually design, right? And then over time, they grew in complexity and they grew in capability and it was just a scientific curiosity for a long time. And then it was like something that only weird nerds did or maybe the military had some interest in it, but you didn’t really see it impact much of our everyday life. And now we have self-driving cars and smartphones. You know, how did this happen? It was all that development, right? It was from the invention of the transistor to when we saw it impact every person’s life in the world was about 40 years. And I would argue that that’s going to be the same for DNA origami. DNA origami as a name came in 2006. But the first DNA nanostructure was invented in the early 80s. So that was about 40 years ago. So you think about it. We’re like at the point where silicon based technology was in the early 90s or maybe the mid-90s. Like we’ll see the first Google in a couple of years. And then after that is just you know, it’s gonna be exciting. So you think about this: what is the self-driving car or what is the smartphone of DNA nanotechnology?

SI: Yeah, that’s a really good question.

I: Have you thought about that answer?

PK: Me?

I: Yeah!

PK: I want you to think about it. I have my own answer. I’m sorry. [laughs]

SI: The interviewers have become the interviewed, huh?

PK: Yeah, exactly. No, that’s literally what we’re working on. Like that’s what we do in my lab. We try to think of “what is the flying car or the autonomous drone” or “what is the VR goggles?”

SI: I know it’s been discussed a lot, but I don’t know how feasible this is, especially with DNA origami. Um, sorry…but like the concept of like Eugenics and like designer babies like…could that…could that could that be like…you know be a self-driving car of the future…however, terrible of a concept it be?

I: We don’t want to go that direction though.

SI: Yeah, we don’t want to go that direction.

PK: I mean all of this is…Every powerful technology has you know, quote unquote “good and bad uses” and it’s our responsibility. Like the people like me who are developing these technologies are responsible. We are responsible, right? We are responsible for which direction we take this and how we shape policy to prevent the potentially harmful outcomes, right? So it’s my job. And if you ask me like what do I do on a daily basis? Like it’s just as much making good things happen as preventing bad things from happening. I don’t think DNA origami in particular has any, you know outside negative potential. I think actually Gene editing is probably the more risky technology here. But even so like, you know gasoline is flammable and it, like, powered our cars for 100 years and most people are fine, right? You could argue that maybe it’s an outdated technology now, but it’s not like somebody looked at gasoline and was like, “oh it’s flammable. It could be used for bombs. Like let’s not make cars.” like no one ever…

SI: Yeah. We have to have an episode about bioethics.

PK: Absolutely. I think ethics is one of those things where a lot of scientists see it as a chore or as like a side project or something that we can do on the side, but I think it’s absolutely central to everything we do and the more profound our work, the more important the ethics are. I mean, you’ve probably all seen Oppenheimer, right? That’s like the perfect example of someone who pushed technology and then had the biggest ethical responsibility as a consequence, right?

I: Yeah, it’s so funny that I don’t think you guys know this about me but I teach graduate students about promoting inclusivity in science. And I basically have a whole section on eugenic, scientific racism, and a whole bioethics part of the class, and I’m also doing an internship right now at the NIH office of science policy where we’re having all these discussions. You know, so I feel like I didn’t tell that part of me, but that’s what I’m doing.

SI: JP lore drop?

PK: Yeah. No, that’s That’s amazing. That’s amazing. I think that if there’s something I could advocate for in science in general and for the next generation of scientists going into this is… “scientist” is a job title. It’s not who you are, right? You are a person and you have to have all these components that make you a person, right? Ethics, inclusivity, being aware of your own biases, being aware of the structural constructs that harm certain people more than others. Like, we’re all complicit in it, right? We’re all either benefiting or being harmed by it and just as much as we do what we think of as our main job, the more important science we do, the more important it is that we recognize all these other parts, because they’re all part of it.

I: Yeah, 100%. So I have some last a couple questions for you that are a little different from ones you just got. Are you ready?

PK: Sure.

I: Alright, so the first one is: if you in Rober were in a car together and you both just finished like a whole season worth of YouTube videos. You’re driving down the Pacific Coast Highway down to San Diego, let’s say. What two songs are you listening to, or what two songs are you showing him?

PK: That’s a great question. I would like to take this opportunity. I really enjoy the fact that you gave me two songs because it would be too much pressure to find the one song that accomplishes what I want. But what I would want probably is to pick two songs that are as far apart on the spectrum as possible to explore the dynamic range both of like emotions and conversations that come out of it as. So I would pick…So I would do basically classical to death metal, which is two genres that I both enjoy very much. So when I was in high school, I was like such a guitar nerd, like, I played guitar classical guitar. My favorite classical guitar piece is a piece called Koyunbaba by Carlo Domeniconi. I think his name is… is Italian composer and look this up like Koyunbaba is like incredible. You just like put your headphones on, turn off the lights. It’s a 20 minute piece and it has four parts to it. And it’s just like you’re transported into another world. It’s absolutely magnificent. It’s the mindful inducing song ever and it just like turns you inwards, right? And then the song I would play is probably one of the songs by In Flames. It’s a… it’s a heavy metal band from like the 90s that I listened to as a kid, and yeah it and it’s just like the darkest stuff but it’s like melodic dark and kind like… it’s the kind of thing that just like resonates with your entire body. I felt that the pulse of this song is like equivalent to your resonant frequency as human being if you were a cantilever, right? So it’s like that’s why people head bang. It’s like that’s the resonant frequency. So those would be the two opposite poles.

SI: You think Mark Grover’s bopping along to those?

PK: No, but that’s the whole point right? Like he listens to the songs he likes anyways, right? [unclear] –people out of the comfort zone.

I: Alright, two more. So one the first one. Can you write those in the chat so we can share them in the show notes? I really want to hear him now and I want to look them up.

PK: Yeah.

I: Oh cool. Two…So what do you do outside of science, like you’re in San Diego, it’s a beautiful place here in California. You know the motherland that’s where I’m from. I love going to Yosemite, Joshua Tree. What do you do outside of science?

PK: Uh, yeah, I do a lot of physical activities, yeah. Yeah. I love climbing…like rock climbing.

I: Oh cool!

PK: I love mountaineering. Since I moved I started surfing. I try to surf a couple of times a week, that just below [location] is actually one of best beach breaks in all California and it’s yeah…I just do things outside. I feel like science requires me to be indoors a lot and especially growing up in Sweden. I really appreciate being outdoors when you can, which is all the time now. So yeah, so that’s what I do. I run up mountains and I surf waves and I am just thankful to be here.

SI: It’s crazy. We went full circle to our very first question about nature of the outdoors as a kid.

PK: Yeah.

I: And for that we need to end it there. Thank you so much for your time.