 Boom, what's up everyone welcome to simulation I'm your host on sake and we are still on site in Boston, Massachusetts We are actually in Cambridge at MIT the Massachusetts Institute of Technology We are at the media lab right now and we are going to be talking about all things genetic engineering We are going to be talking a lot about biology. We're gonna be talking a lot about these different nuances of what's gonna be happening going into our future I'm super excited to be talking to Pranam Chatterjee who is a He's a graduate student here at MIT's Media Lab pursuing his PhD in media arts and sciences Pranam Chatterjee, thank you so much for coming on this show. Thank you for having me really appreciate it It's nice to be here super pumped Pranam's awesome. He's like a he's like the second generation of Taking the CRISPR technology and exploring it and moving forward with it and discovering new things with it and He's also really good communicator. He's teaching a class right now about genetic engineering and And I'm really excited to talk with him about all this different stuff. So Pranam, let's let's start with you know Let's start with who you are So how did you first even realize that you know You know where you were born how'd you start finding your interests at Sedger tell us about that? Yeah, so I mean I grew up in like the I was born in Florida But I grew up in the kind of the middle of Georgia suburbs of Atlanta And so like that really framed a lot of my upbringing my dad was a scientist my mom was a scientist So they were really they kind of instilled within us that mentality I have a twin sister as well who goes to MIT so my whole family is this really scientific Kind of like eclectic family growing up You know in in America were second were second were immigrants my parents are immigrants my sister and her first generation Americans and so with that background, you know, we were able to explore a lot of stuff obviously You know science is a cool part of our upbringing But you know at first I was really interested in a lot of different things and one thing that was really cool about Georgia and living in I would say like the Bible belt of sort was to was to interact with people have a very very Different mindset than you do, you know, like everyone down there. It's pretty much, you know, a very strong Religious probably very Christian, you know, and so growing up I was very interested in like just how people thought You know the different world views like what was the best way to understand how the world works? And that got me through, you know, different different studies different fields of thought I I know it's kind of funny, but I spent a lot of my time Growing up reading a lot of religious texts just to get to know people around me You know like the Bible the Quran the the Torah, you know, like I spent a summer to Buddhist monastery, you know like religion was Really interesting to me. My parents were super religious at the same time And so it was cool for me to see how that world view right the world view of You know a religion from a religious studies background Could inform how people saw the world but at the same time approach the world in a more in a rational perspective That's kind of what has led me to who I am today Yeah So as as you say that I'm thinking about all of the different ways that people Pick up religion when they're really young and then they slowly sort of start to kind of realize that it's all about the feeling of the spiritually kind of transcending oneself and and the ego and more so about this collective unity with Infinity and the cosmos and etc. And and this is so as I think as we're as we move forward actually Let's let's jump back into because you started picking up theology. You had to get to scientific parents Yeah, yeah, it's kind of weird and I know why I like even jumped into that was because it was such a like Major player in my life not because I'm particularly religious my parents were like I said, but But you know like the really the one the fun thing about it is that science To me and to what I saw was one way of Accumulating knowledge about the world like how did it work? What is the best way of like understanding the evidence around us? Well religion was you know another way of thinking and and and and that's why when I went to college for the first time I went to Dartmouth college for my first two years of undergrad. I wanted to study this You know, I spent a lot of time reading text as I said I then spent a lot of time going to like monasteries Churches synagogues learning about this and then like what is the next obvious step? You know while appreciating all the other fields the obvious next step for me was to study Do religious studies in college? So it's very different than what we're talking about here today, right? Like talking about genetic engineering so but I actually majored in Religious studies at Dartmouth college for two years. I would actually concentrate in East Asian religions Yeah, like you know confusion is a bad mood isn't like you said like really things that are very different than what I do now I later realized that the The way I wanted to view the world was through reality how things have worked The kind of the mechanisms why they work and and then the nature of evidence was super super exciting to me Therefore, I'm here now. I transferred to MIT from Dartmouth where I now study where I studied computer science and molecular biology And you know the rest is history, I guess so I want us to To to really realize why computer science and molecular biology is such a crucially interesting pairing Yeah, because the With code with you know with code in in zeros and ones and binary and then with A's T C's and G's The DNA bases that there is such an eerie similarity in being able to understand biochemical pathways Exactly, and that's I think a new way of approaching biology I know biology is obviously been a discipline that's know has its way of own way of doing things for many years And you realize that if you're going to come in and be a major player like actually make a contribution to it You need to be able to think in a new way in a different way Maybe even in an advanced way like so that you can really push the boundaries of the field you're in and you know I realize this that when you're going into biology or going into any field You want to do something that people care about that people think are cool And we'll have a transport formative effects on what humanity is going to be so I said really the two things that will do that are AI artificial intelligence, we all know how that works and we all know how that's really pervading All these different fields, but also gene editing right like and just like molecular biology the tools that biotechnology is giving us You know it's changing how you know just curing diseases changing agriculture changing bioenergy It's affecting a lot of fields and so if you can not only can emerge the two fields You can really create the synergistic effect that allows you to push forth, you know Research discoveries that people care about people really I think are excited about what we're doing here in the lab And I hope it stays that way. Yeah, I'm happy that you really identified that that But that biotechnology is ever is going into everything as well as artificial intelligence really it's so interesting how Biotech's kind of like is like the secondary like AI's of course. There's a lot of overlap Biotech is just going into so many different places from the food that we eat to the way that we treat our own Diseases and ailments and prevent them as well Okay, so So it's it so even though you made the transition to MIT and you figured out you wanted to do Computer science and molecular biology What from there got you to the genetic engineering specifically and CRISPR? Yeah, you know, it's not it wasn't linear, right? Like it's not me just jumping in from theology directly into CRISPR genetic future, right? Like it's not that easy I think really what made it so cool was that I was able to You know stay in a field that was also really interesting in the last five ten years in some in terms of scientific research And that's the field of immunotherapy right immunology of sort So I actually spent most of my undergrad even while a religion major My over-the-summer's and through the school year I'd work in a research lab studying this one molecule and that was called the molecule cupid one So I don't know if you know what PD one is But it's actually a really what we call a very hot immunotherapy marker Meaning that it's a molecule that is easily targetable if we target it You know, we have the ability to you know affect a lot of different things that are happening in your body Especially when it comes to diseases like cancer for example, I'll tell I'll just make it really brief But PD one is on the surface of our immune cells, right? And if we're able to Bind to PD one if a cell another cells able to bind to PD one it can actually turn off the immune system It'll turn off those immune cells They can't you know protect your body like you know immune immune your immune system does and this is what a cancer cell tries And that's exactly right you guessed it you you took it against the out of cancer cells playbook. They literally will bind to T cells prevent them from being able to attack the tumor cells So in the tumor environment These cells are turned off and so a lot of what I did as an undergrad was First understand how this happened the pathways within the T cell that allowed them to get shut down So I one of my major papers I published with my lab as an undergrad was understanding the metabolic Pathways within the in T cells that have this you know PD one shut down occurring And that way we were able to identify what are the important features of this molecule that made it so special And then the big the big you know biotech pharma interests came into this field Just like maybe about five ten years ago like right like in the kind of like in the middle of my undergrad People started realizing hey if we do something with this molecule You know this this could be a really great treatment And so I don't know if you've heard of the new drugs called ki truda and optivo They came out of Merck and Bristol Myers web I was working at Pfizer over the summer where we were working on antibodies for PD one You know if you can prevent the PD one antibody from being ligated you can keep those immune cells on and that's what that Antibody did and so now we're you know able to you know go after disease like melanoma blood cancers like lymphoma leukemia in patients that have PD one and they exhibit pretty amazing results as a result of this treatment Interesting so the first foray was into immunotherapies and then specifically to make sure that that immune cells were able to Hold to cancer cells couldn't block that PD one receptor immune cells could Continue hunting exactly for the cancer cells properly identifying them and killing and killing them and that's powerful Right because this is not like standard cancer therapies that are you know very Invasive they're not like chemo therapies that can kill healthy cells They're not like radiation therapy that can you know ablates a large portions of like again You're you're saved the immune system. You're healthy immune cells. So this was a targeted Treatment for these patients and they're it's now two of the most I would say the most prescribed cancer drugs for our patients with these Yes, that's also so crucial that rather than doing this in full-body nuke Yeah, but it's a targeted molecule that comes in and goes straight for exactly one exact and I think I think that is You know a movement going forward one is still a pretty amazing field is like how can we use? You know what we call these? Antiblocking antibodies to to affect the immune system so that you stay as healthy and active and your your body stays as healthy and active as Possible always looking out for anything that could go wrong. It's a very powerful approach And I hope it's something that you know continues to drive the field of therapeutics going forward Yeah, and you were doing this with Harvard Medical School and Pfizer and then you Come to do the graduate work. Yeah, so I was like had to make a decision I think at that time we realized that you know immunotherapy had really reached its peak, right? Like this is we've discovered this a set of new molecules like antibodies that help treat it now You know really what is the next great? You know thing that'll You know like biotechnological tool that'll take us into the future and clearly that was CRISPR You know gene editing in general because you know, guess what when you can edit genes you can edit You know you can affect fields like agriculture you can affect the bioenergy you can affect You know the ecosystem shape the ecosystem simply by editing living Organisms and the DNA that makes them up And so I realized that you know if we're if you're gonna really make a you know big splash And you're gonna Train on top of this you want to do it in a field that matters and I think CRISPR is a super cool field And I'm not I wasn't one of the first people to do it But I'm lucky to be in it right now a reoccurring theme that I'm seeing from Pranam here is that he is Going to the edge of what's known like the edge of immunotherapy then he's trying to you know, which spurred off these For cute for curing melanoma and blood cancers and foam etc And then you know for working on that and then there's a new edge and that edge is the overall edge in genetic engineering And you and you want to be there we talk about that a lot is striving to get out of the base camp of knowledge Where a majority of people are? It kind of in just day-to-days and aiming to go to the boundary of human knowledge Yeah, and I'm glad that you have that as this powerful like I want to know what's going on I want to know what's going on genetic engineering want to be out there. I want to be studying it I want to be teaching it to be advancing it and you have already been a huge part of advancing it right and that's you know That's a motivation. I want to Like you're you know you have a lot of different responsibilities as a scientist even as a person who like went to MIT I feel MIT is cool because you're really thought to think outside the box You know we're in the media lab of all places where I'm not even in a standard bioengineering program or biology program We're in a place where you can literally go and answer whatever questions you think are interesting You know my professor is one of those people. His name is Joe Jacobson. You may have heard of him He's the guy who invented the the Kindle technology the E Inc. So he's and guess where we are now We're doing CRISPR so like the fact is that it's cool to move from field to field always staying at the edge Like yeah, can we can we design tools that you know? We'll help us to take these for example gene editing Into the future so that more people can use it more people can use it safely and It can go to a lot more places and that was my motivation Yeah huge shout-out to the media lab because the when you come to the Boston area You have to come to the media lab and come and look at all the different fields that the media lab is exploring at MIT This is this is what the cutting edge is they are in so many ways exploring that cutting edge and Joe Jacobson exactly Joe Jacobson shout-out as well Okay, so let's actually talk about where we're so we had a discovery about five six years ago Yep of CRISPR-Cas9 Accelerating our ability to do genetic engineering Yep making it very easy to target making it very easy to make the genetic edits We need inside of specific genes that we're looking at cells that we're looking at exactly So then now we're kind of following there's like a big wave that's coming after that And it's this wave of people like you that are like really understanding. How can we make this better? How can we make it more right? Yeah, I mean first of all like Many shout-outs to the guys who really made discovered this thing. It's it's amazing CRISPR is not something that we invented It's something we discovered but To be able to repurpose a system that was originally an immune system for bacteria bacteria into a gene Editing tool for to go into humans and to plants into animals is amazing first of all So shout-out to all like the people came before me in this field and shout out to bacteria Yeah, bacteria nature that made this amazing system three and a half ish billion years Evolution of evolution which is why bacteria has so many of these different ways of protecting themselves, right? And that's what we do, you know like bacteria can protect themselves is so elegant of a fashion You know we can definitely see how can that be used in a in a in an elegant manner so that it can be used to you know treat diseases or or you know you for agricultural purposes whatever and so you know as the second generation of CRISPR scientists as you said said before My job or my interests lie in really not just tinkering with it But kind of revolutionizing the technology yes first of all today is safer, right? So we can make sure that this technology doesn't do what we don't want it to do and secondly Give the ability to go and make the changes you want to make don't be limited by what the Regular CRISPR system has the limitations it has and so you know at the early stage of our you know research In CRISPR in our lab, you know me and a few other grad students in the lab Know a shout out to know I got a shout out everyone because they all it's all a team effort You know we do it together, right? But you know like what we really did focused on first is making it safe because if you don't make the system safe You're not going to be able to apply it in all these different settings And one of the things that really is kind of dangerous and like you really want to avoid is something we call off-target effects You know if what if just say you have a gene or a specific target sequence that you want to go to but there again There's another sequence somewhere else in a different gene that is very similar. Maybe one or two base DNA bases off That's not very much different Sometimes the original CRISPR system will go to the correct location Which is supposed to go to but also go to the wrong gene go to the wrong Location and that's what we call an off-target effect and it's very important that we Figure out solutions to make sure that that doesn't happen because once you go into a clinical trial You don't want to accidentally edit the gene that codes for brain function or heart function or anything like that You want to just edit the gene that has the mutation the change the abnormality and make the change and be done with it And so that's what we focused on What we what we built was a system that? Essentially destabilized the CRISPR system in general at the wrong site But kept it stable at the right side so when it's stable it can do what it needs to do it can Target the spot it can make the edit if it goes to the wrong spot You don't want it to do it and that's what our system did you made you destabilize it when it was at the wrong Correct and people have tried to do it before there are ways to do it where you could take the enzyme and you could You know reduce the charge of the enzyme so it doesn't bind the DNA as strongly De-stabilize the DNA so that it only binds strongly when it's at the correct site But not when it's at the wrong site so that was a protein approach But guess what every time you have a new protein you have to you know go through the long arduous process of making sure that protein is Good it does what it needs to do and all that so we were like how about the targeting molecule in CRISPR The way CRISPR targets is by using a piece of RNA RNA has bases so it can bind to DNA Which is what you want to do and so Right the irregular system uses RNA Take attaches the enzyme to the RNA and takes it and makes the edit however RNA binds to DNA when it when it when it comes to the correct spot or whatever spot of DNA it's at However, the repulsion between RNA and DNA is not actually as strong as a repulsion between DNA and DNA So we thought if we could add pieces of DNA into the RNA molecule We could de-stabilize the CRISPR system at wrong sites So it doesn't work don't want to edit those sites and only keep it stable at the correct sites And that's what we were able to do and so we were really excited about this technology going forward in clinical trials To make very safe, but still very effective CRISPR system That was what I did for the early part of my master's thesis Yes, yes, and then that that definitely led you because you're already starting to work with the Cas9 System then you're able to really get into more nitty-gritty off-targeting was one thing So you were solving off-targeting exactly huge and then then where'd you move into after that? So like so I was saying there's really two main limitations of CRISPR I'm using it for gene editing there. They're quiet There are others but the two main ones is first the off targets Which I feel like you know that our lab was able to address we were able to dress together and then the second Real interesting limitation that you know I previously said that you know CRISPR could go to any gene But that's actually not true. I kind of lied about that CRISPR is actually Has its own targeting limitation. So say you want to go to a specific DNA sequence, right? It's it's you know 20 DNA bases long you want to go there, right? But if you want to go there you all you need two G's like ACG and T you need two G's the site So if you don't have those just say you want to go to a specific gene you that you want to specifically fix But it doesn't have two G's so at the end of the 20 base pairs Of the DNA bases and you're targeting you're targeting you need two G's exactly for the For CRISPR Cas9 to be able to identify that as where you want to exactly That seems like such a big limitation Right to what you can do. So you can even do the math in your head, right? Like one over four to the second is how many times you would see it two G's one over four to the second is one sixteen But if you can actually go to either Because DNA is double-stranded we'll liberally say you can go to what one eighth because you can go to either strand So you can go to see CC or a GG, right? So with so with the normal CRISPR Cas9 system, you're limited to editing an eighth of the human Yeah, even that's even a little bit liberal to get like you're giving it a little bit of flexibility there But so it is imperative for us. We realize, you know, we're not gonna really be able to use this system if we're Restricted by this limitation why because if you just want to like disrupt the gene You know if you just want to like, you know, you know get rid of a specific gene in your body Or you just want to insert it some somewhere in the bot a new gene somewhere in the body you can go Anywhere in that gene that gene is pretty long ten thousand bases long You're probably going to find two G's somewhere, right? But just so you want to fix an exact spot someone amute disease is caused by a specific mutate like sickle cell anemia It's caused by one specific Mutation you want to fix that specific mutation. So if you cannot go to that exact spot, you're pretty limited So our goal was to actually expand the range that a CRISPR enzyme could go to and you know like Our lab is pretty small, right? We're like me and I think you may see no in the background He's not there right now, but he but he and I you know, we were really intent on finding An enzyme that was broader, you know could go to more places because that would enable us to go to and fix a lot Of things we previously couldn't fix Yeah, and so and there's thousands of Diseases that are the single-point mutations and and the great thing is while we were doing this There's a new technology that was developed called base editing that could just fix that one thing So base editing would be really helped by enzymes that only that can go many places And so that was our motivation and you know We come as as as gene-edited genome engineers at the media lab We're in a really small we're in a small group and we're amongst very few people who do this kind of thing While we're competing and we have a lot of other people also trying to do similar stuff, but in huge labs, right like sick people 60 molecular biologists in a lab and so they're Utilizing very, you know Large-scale experimental approaches to find these new enzymes these new tools that are broader. They're more specific But we know and I and are thankfully computer scientists like you had mentioned before and so we were a Bioinformaticians right like we are really capable of using algorithmic power You know computational power to do the discovery process for us We could write the code and then allow us to discover say a new enzyme that could target more molecules And that's exactly what we did bad. Yeah, I know that That was pretty fun and like we developed this cool pipeline called spam a lot I don't know for those of you who know like the Monty Python reference. I'm gonna stop it right there Anyway, we built this really cool bioinformatics pipe pipeline that allowed us to say hey here all the CRISPR enzymes out there here. They're predicted PAM sequences This is how many bases they need to target and we were able to identify one that only needed one G One G instead of two So if you do the math again in your head one over four now because you don't you only have four bases And if you do it on both strands that covers about one half of The genome so we were able to find an enzyme that has Affinity towards one G and therefore can target about 50% of the genome and that was I think a big Advancement and we were paid a publish in the in science is open-access journal and you know like publish in science is open-access journal Yeah, yeah, it was like it's somewhere that every know like you know people are now starting to really use I you know I'm sending this Enzyme out to a lot of people that try it out You know there a lot of people are interested in using it because now guess what you if you're working on a specific disease If you're interested as a geneticist if you want to study a specific gene You can do it do so much more broadly because you can target a lot more Sequences and that is what our computational pipeline gave us this enzyme Which we then put in right behind you as we're we're in the lab right now We were able to go and test it in human cells that are right in that incubator and show that this That this enzyme was brought that this enzyme could target a lot more sequences than we previously could target So with your computational pipeline You're able to identify ways that genetic engineering can more easily make the targeting and the cutting more Effective exactly and editing more effective then this is called SC SC cast so the original cast 9 comes from streptococcus pyogenes bacteria That's the strep throat bacteria that you have but we have We found a cast 9 that comes from a similar bacteria that is that is found in dogs or in the infects cats and cows Really animals it's called streptococcus canis for the dog for infecting the dog And so that's where we found this new cast 9 and you know that wasn't even the end of the story We were able to use this pipeline to discover another Another enzyme that could go to the other 50% of the genome We didn't cover the other 50% but we found one that needed two a's Yeah, so if you could eventually get to one a right you cover the other 50% Right because you could cover the t and the a on the both strands But two a's already gets you to another Advancement of the other 50% which is a really cool. I thought it cool So together two enzymes that we have in the lab right here, you know Yeah, can cover a significant portion of the genome this so heavily speaks to the importance of a Computational biology. Yeah. Yeah, you know, that's what made it possible Where there's no way we were gonna carry out huge experiments. First of all, we don't have the people to do it Second of all, it's difficult when you're like not, you know, you know, the CRISPR lab, you know, like the big CRISPR labs are capable of doing these things But we we have to take our own approaches and I'm pretty You know, I'm pretty psyched that we could do it pretty so effectively in the lab right here Yeah, it's it's such an also It's it's so Visibly pieced together where it's like this first advancement that comes about five or so years ago And then the second wave including computational biologies Processing and figuring out all the bacteria that's involved. What do these bacteria know as immune in their immune? Organizations that that we don't yet know and how can we apply that to our lives? And so you get to study all that and discover make new discoveries around you Yeah, we're basing it off of what nature is giving us, right? Like they give us a lot of information if you were doing all of this from scratch It'd be pretty hard like you're not we're not as good as nature to fine-tuning Biological systems right and so we're taking a page out of nature's playbook and you know We're we're we're really excited about what that can even give us going forward There are a lot of new Enzymes and proteins that have really cool properties that we're really excited to exploit in the future And it's it's also nuts because this is already now We're not we're talking because you found this you you only need a single G Yeah, half of the genomes available to make genetic engineering edits to it it it becomes now a We're not ignorant anymore So if we know that we're screening ourselves like if you are about to Have you have a partner and you're about to pursue procreating having a child into the world screen yourself Have your partner screened and then you know better if you are going to pass along Mutation that's going to cause a disease correct and then furthermore is even when it's even when the process does start of of the fertilization of an embryo that You can still then check again to make sure that it's absolutely doesn't have the mutation And if it does have the mutation you have full control of making sure your child does not have that disease now Correct, and this is even today for 70% of all of single-point mutations Yeah, yeah, and then we can fix those right and that's what's powerful You know like we have like first of all, you know You have just a few years ago the lot of these genetic diseases were incurable and with the advent of not only this new CRISPR technologies, but base editing right the ability to flip a Single base as I said before that these technologies together make it really easy like you said 70% We could we can target and so when you do get to that stage where you know You want to make sure that your offspring doesn't have a genetic disease You have one of two options really you you if you think that the pop if you know that the offering will have that Disease you could go in with the CRISPR system and and just design You know an RNA that targets and the enzyme that goes to that specific location and make the edit right after fertilization and then make sure that The cells were properly edited the embryos were properly edited and then re-implant that back into the mother So you know for a fact that your child will not have the disease at the same time a more conservative approach that Still works really well is you could just you know do in vitro fertilization and just make sure that the embryo that you implant Doesn't have the mutations you have options and there's I don't see a reason why genetic diseases is gonna are gonna like last For a while because we have the tools not only to make sure at first you're go safe but if not Go in and programmably change what you need to change and what we're doing here in the lab Is giving you the tools giving you know the general community the tools to be able to do that and the beauty of this all is It's not even just limited to medicine It's you can do this in like plants in in for bio biofuels You know like like we're able to even make malaria mosquitoes resistant to malaria by Introducing genes that confirm malaria resistance and into these organisms and have that reproduced like we're CRISPR and gene editing has Enabled all of these technologies that will make our lives better that will make our technology safer And you know overall will hopefully make society a better place than it is today But you know it's young and we're we as a me as a CRISPR 2.0 scientist Yeah, it has to make sure that that we hopefully will get to that stage. Yeah. Yeah There's there's a an interesting sort of like big history understanding of things where you look at humans trying to figure out how to How to do breeding within genetics? Yeah, and it took so long to get what we wanted Wanted you know like like like even when you just say just say you wanted you're in a research lab And you work with like mice right imagine how long it would take to get the mice with the exact like What we call phenotype like kind of like how An offspring mice that has the traits you wanted to have to study it'll take you months But I take you years in the lab to do this Iteratively until you get a mouse that reproduces well now We can literally just go into an animal into a plant into you know one day into a human and then be able to Make the change. Yeah, that changes permanent, right? Yeah, that's what's beautiful about the system And that's what gives us so much power at the same time There's risks and responsibilities that have to be assessed But we're also that's something that we also work on and we do that by educating the people around us about the system these Yeah, these These risks are and these ethics and these geopolitics around these technologies are nuts It's pretty crazy. Yeah, and it's and there's a lot of pieces that come into this puzzle We were you know geopolitics come into this puzzle We have the ethical quandaries that come into this puzzle. What should or shouldn't be ameliorated as a as a disease There's the ethics of who is getting the access to the augmenting Technology and that's that you know that as Christopher scientist you have a sense of responsibility To make sure that the right hands get on it and all not only the right hands of the people who understand how the system works Unfortunately, it's not always how it works and I'm sure you know all of you guys out there You know everyone probably has heard about the CRISPR baby scandal that happened in China where a scientist called Ho-jen Kueh Was able to edit the That the embryos of two babies were now born Lulu and Nana with their names and Unfortunately, this was our first foray into human embryo editing, right? And you know that's that was that's something that we weren't ready for as CRISPR scientists because we're we don't feel that you know We've done all the checks needed to make sure that CRISPR does exactly what we wanted to do it all the time and you know that that that you know that kind of like that Apprehension manifested itself where the edits for these two children were not expect. We're not what was needed What this guy was trying to do was prevent HIV transmission or pretty much make these children immune to HIV by editing their gene They weren't trying to cure a genetic. He wasn't trying to cure a genetic disease. He didn't even like really prevent them from Getting HIV what he did was essentially gave him an enhancement a protection of sorts and Not only did he want to do that he also didn't do it in a very clean fashion You know like unfortunately the edits to Lulu and Nana were not exactly what is needed to make sure that you have HIV resistance in the future So the point is that you know like this the geopolitics as you said are you know super critical We want to make sure that it's not getting into the wrong hands and you know the regulations are there So that until we're ready to go, you know, nothing crazy happens, but because something like this happens, you know What it does is it decreases? Sometimes it decreases public trust in in your technology people are scared of it, you know imagine sometimes it also makes it more easy easily It becomes more in the public eye, which makes it more receptive so that it's not like oh What is this gene inch thing but rather you actually have seen genetic engineering war in the news and whether it's a bad or good thing And you know like I'm sure you've heard of like the bio hacker community, too They get you know people who are not like CRISPR scientists They actually will be able to get their hands on the CRISPR system and want to do stuff with it You know hopefully not injected in themselves. I'm sure I think someone has done that But being able to use it for their own purposes, which is fine in itself But as long as they know and they have an understanding of how to do it and how to do it properly You know that that is the main ethical question Like at what point do we let people let this technology run free as the scientists who are developing the technology itself? So you know it's not an it's not an answered question But we're still like figuring we're ironing out all of those details and where do the scientists work with the politicians and the ethicists and the philosophers and When are we actually ready because sometimes when we look at civilization? Yeah, it's it really doesn't look like we've advanced our way out of the fifth grade quite yet Yeah in terms of our own ability to not get into wars and to not pursue Conflicts with each other, but rather have that sense of unity right we have to mature as well first correct Yeah, and that's I think I feel like I said before I as a CRISPR scientist feel a responsibility to educate people about how CRISPR No gene editing work. That's right. It's not going to just be like you know the select group of people who are going to be using it You know, it's it one is going to come to every it's going to be in it's already becoming Thousands and thousands of people soon. You're teaching a class right now Yeah, it's going to become millions really fast And it's great to have those millions because you also want the creativity of those millions exploring it It's wonderful because this is one of those technologies that will use the societal like collective knowledge To advance itself when a technology affects so many people, you know The input of everyone comes into view and if that input is an educated input, right? If people understand how the technology works at its foundation what its applications could be then we have an informed society and we have One in which the technology will be used properly and for the right purposes I'm not going to be the one who defines that my goal is to build the technology and then teach it How to use it to people and that's what I'm doing actually this this this January I'm teaching a CRISPR class here at MIT teach us about it. Yeah, so like we're really it's really cool I mean, I actually explained a lot of what I'm talking about in the class here today But but the class is really what really a short for for a session course where students can come in They can learn about how CRISPR works like the the system the bacterial system Then they'll learn about the mechanism of how it works like what are the pieces of CRISPR that are important for you to do gene editing? What are the applications and you can put it to so that you use gene editing in the right app in the right ways? And then they'll actually come into this lab right in here and do CRISPR experiments This is where they can realize this is a responsible way of doing science whether or not they're scientists in a different field Obviously some of them are like biologists chemists They want to use the technology for their research, but there are people who are like policy policy people and you know like students who are just like there to learn about cool new things who what who will come in Contact with the technology here in our lab and do it in a really fun safe manner too And so they can go out and you know be able to use it very in a very in a responsible manner And you know the final class will talk about what we were talking about today ethics, right? Like how how do we together as a society face the problem of you know changing who we are as people? Yeah, right. Is that a good thing? Is that a bad thing? What do you think? I want to hear these opinions Overall good thing. Yeah overall good thing and Definitely it's the next evolution and we need and we need to be wanting to get drive ourselves to the next evolution In a way that is steering ourselves not off the cliff, but I'm more Towards the up the up the mountain. Yeah, I agree with you. Yeah. Yeah, okay I want to ask you what is going on with your technology next because you know because you're doing this computational biology It's opening up the doors in so many new ways and you're really excited about that So tell us more about where so we're really interested in a few questions, right? Like I especially me is going forward is I really still want to get to the hundred percent rate like a genomic coverage We're continually improving our algorithms. We're improving our experimental techniques So that we are able to do that hundred percent genomic coverage That would be cool right like then you really have free range on where you can go in the genome and we're close You know, we have two or three enzymes in our hands that could be great methods to engineer Also, we have this computational tool that can take us and find You know new enzymes that could be very powerful. So that would be a really critical goal that we're working on currently a second Goal is definitely to go back to this idea of base editing, right? Like as you said before the current set of base editors can go and fix about what? 70% of all what we call pathogenic sims Mutation single mutations that cause disease And so that it would be wonderful again to really treat the other you know a certain number of diseases Not only because it'll fix, you know mutations that cause disease But also gives you a lot more power as a genome engineer in whatever Application to be able to flip DNA bases the power of this technology lies in not having to really Make too much of a change, right? You don't want to have to cut a deep piece of DNA every single time you want to make a chain You just want to do a nice clean Chemical transition of a base just say you won't have a C right a CG and T for your DNA Just say you want to go from a C to a T. We can do that already How about an A to a G we can do that already and so, you know We have the ability to do these small changes But when you get to like things like going from an A to a C or you know an T to an A That gets it's getting harder, you know We're not and it's not as easy to do all these different base conversions right now We can do four of them. There's 12 in total, right? If you do the math, there's 12 DNA based Conversions that you can do so I really am interested in designing new tools to be able to do every type of gene DNA edit as you can couple that with this Expanded targeting space now you can literally do whatever genome editing you want to do I think that would be a great goal for myself and through my PhD. Awesome. Yeah expanded targeting and and All base conversions all base conversions. Yeah, that would be like, you know, like you have a lot of power That's a lot of yeah, totally. Yeah, that's a big Moving of the human knowledge edge forward. Yeah, I love that. Yeah, see this is moonshots right here This is how you do moonshots. I'm serious to all the young people. You're 24, right? Yeah, I'm actually 26 Yeah, he's 26 rounds 26, but when you look at young people in their mid 20s. I'm 26 as well That you got to have moonshot goals. Yeah, and you have this moonshot goal You're hearing it right here. I'm pushing the boundary of knowledge forward past What is known and doing things like helping really move the ball forward with Eradicating disease making augmentations and so much more huge huge huge and computational biology is so interesting. I love it I want to know post. What are you thinking post? What you want to get done here in the PhD. Are you thinking entrepreneur? Professing. Yeah, where are you thinking? Wonderful about this field is that it's super open, right? Like you have Everything you build can be very powerful, right? Like people want to use it So there's a power in like the IP that you hold the patents that you have that you know encompass all the work We're doing, you know, it would be really cool one day to like, you know Do a startup or be an entrepreneur because you can bring your technologies to a lot of people at the same time I'm always interested in solving new problems, right? I'm the person who switched from like religion to immunology to computers. I'm like, you know, like I love exploring new fields and I think an academic setting is one of the best places you can do it I think I'm naturally built for a place that is, you know, free thinking exploring, you know Solving cool questions always looking for the new thing. So, you know, my whole dream my whole life was to be a professor And, you know, that would be wonderful. You're a good teacher. I don't know about that But like really another like we can't even discount like going into like something like industry because like I said Yeah, you remember the Optivo and Kichir the yeah, these big drugs, you know That are gonna cure a lot of people are coming in industry So, you know how to apply what's up here and what's being done into the world and so that you get it out there And so like you feel a responsibility to do all of these things, but you can't do all of them You have to really pick what you want and I think I'll save that judgment till when I'm done with the You're ready? Yeah, yeah, but you know like I'm excited I think like as long as you're able to solve cool questions and do good science like I'm happy How about we ask you Okay, so there's What do you think is the role of regulation in this being part of the second wave? What do you think? Yeah, it's it's it's something that you see is very important But you also realize is very difficult, right? Like you know that it's important to be able to make sure that it gets in the right hands Like you said, but at the same time you also want to make sure that this technology is used as broadly as possible because you can you see First hand when you do your experiments What this can be, you know what what this technology can be not like again? I'm not the person who discovered CRISPR I'm this person who's making it so that it can be used by other people for really transformative purposes I am the tool developer of sorts right like Enabler like I enable people to do it And so you want people to be enabled you want them to be empowered to do different technologies not just for medicine But agriculture energy, you know, you know geo ecological engineering, whatever and so You know like I I want there to be the ability for people to do good science and to do good Applications use a good CRISPR for good applications same time. I know that you know we Like as a society we collectively need to decide where to go with this technology Even if I am the one putting in the 18 hours of work in the lab doing it It's not up to me, you know to say where's my technology going because it's not going to just affect me Yeah, it's gonna affect you it's gonna affect all everyone out there, you know, like we we collectively bear that burden And so I'm interested always to hear from you guys, you know people Let us know in the comments below we'd love to hear from you Yeah, what you think about this technology and you know, what can we do as genome engineers to you know To make sure that it gets into the right hands and is used for the right purposes. That's right That's right. Okay a couple quick questions on the way out that we like that we like asking our guests What do you think is a core driving principle of your life? Yeah, it's it's it's it's to make in to make an impact that will lead to more impact Meaning that I'm here doing science so that people in the future will also be able to do good science so that I am you know Hopefully will help cure a disease so that those people who diseases were cured can whole go and make an impact in the world You know, that's me I am I am one point in the timeline of humanity But I hope that time point, you know is has enough push it keeps pushing humanity forward because I believe in What we can do and where what this world can be and you know being able to do gene editing be able to do maybe even some You know computer science and you know understanding even the past with religion all of these things have contributed to like understanding people and Giving them the ability to like make an impact while you're also making it back to yeah Again, this is coming. You're just like I'm going to the edge of knowledge and I'm gonna Pushing the edge so that other people can build on top of that in the future. That's so beautiful. Love it It's fun, right? Like I I have fun every day coming to the lab people say why do you work? Like 20 and 18 20 hours a day. I literally work non-stop because it's fun You know like you got to love what you do every moment of your life Yeah, you know matter what you do whether it's talking to you know people about it by the teaching a class But it's just doing a random experiment running a control You know like like everything is contributing Yeah, you're contributing to the knowledge of the world and and that's like I feel very very lucky to be able to do that All right I have a good question for you because you spend so much of your time understanding the Computation in biology. Yeah, so then you must understand then how a cell could be potentially computed all of the functions So how could all of the civilization evolving on a rock be computed? So do you think we're in a simulation? I? Would not I am not gonna answer that question, but I think you're on to something really really good there I'll have to sit on think about that expand more. Why do you why do you think you know it's it's Computation is so you know you realize it doesn't come out of nowhere, right? like the way life is Form you even CRISPR right CRISPR is like such a beautiful thing that nature and evolution has given to us you think that there is some Ability to understand the patterns right like there's there is some programmable elements to how we as humans to how Society how reality is programmed that you're like this is you know it would make sense for there to be some alternate explanation for what we're living in and and You know I'm doing my part to like understand that small portion of it But if we one day come to the understanding that this is all just one big simulation I'm not who am I to say that's not that's not true, you know I'm all for evidence and you know We're digging into the code of the simulation to figure it all out what we're doing right now we're gonna we're gonna simulate the Evolution of a civilization on a rock just like earth orbiting a star and we're gonna fast-forward Until this point Okay Okay, and last question that we like to ask on the show what do you think's the most beautiful thing in the world? Most beautiful thing in the world. Oh, I don't know I have to say I Don't know I have to I have to go with like What I have to say send the central dogma of molecular biology like I just think it's it's it's why we exist You know like I am pretty practical person Yeah, the central dogma is like the ability to go from a DNA to RNA to a protein which codes for all of life Yeah, if that prop that process is so beautiful and if and if that doesn't exist We don't exist nothing like our ability to process all this doesn't exist And I know it's a super scientific answer and it's like no, it's great But that is great is literally like it every day. I'm in the lab. It is and every day I just live I'm like this is this this is a central dogma of molecular biology. Yeah, I love it If you're so passionate about what you do that the central dogma of molecular biology becomes the most Beautiful thing in the world probably really crazy. I love it No, because I'm really crazy too and a lot of people like us are really crazy in love with what they are building And those are the people that are pushing and pushing the brinks and the edges So I love that about you. I'm glad that you answered it that way. It's really beautiful Okay, I feel I feel like we did a really good job. Yeah, we did a really good job from this has been such a pleasure Thanks for having a fun time. Yeah, super fun time Feel free to come back if you guys out there want to know more about the Media Lab Feel free to you know like comment and I'm happy to like I'm happy to like see what everyone has to say totes Yeah, we got so for you guys. Thanks for tuning in we greatly appreciate you so much We would love love love for you to comment below with your thoughts about what we talked about regarding genetic engineering and all of the Nuance, so let us know what you think Also, do check out Pranams links in the bio below also Definitely build go and push the edge of what's known in our world go and do it Yes, manifest your destiny into the world everyone join us on Patreon links below because we want to continue supporting our efforts in going scaling and take having these conversations shared with you around the world We love you so much. We'll see you soon. Peace