Latest / Art of the Question / 7 Fascinating Facts About DNA - Sander Wuyts - #19

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7 Fascinating Facts About DNA - Sander Wuyts - #19 · Art of the Question

• Julius Moorman: When did you first get interested in DNA and why? My pleasure to be here, Iulis. Every kind of occasion to talk about DNA is ⁓ good for me. It's always an excuse to put on my DNA t-shirt, so I have a DNA shirt here. Ready and waiting for people that want to talk about DNA. My DNA experience, I think it actually started in high school. when I was just a student learning about a lot of things. At that time, I wasn't too sure where my career would go, but I was definitely interested in sciences. And I think it was in biology class that the first time the molecule DNA was mentioned. But I think it was started even a little earlier with the whole field of genetics. And I think one key person there is a Gregor Mendel. that was mentioned. I'm not sure whether you ever run into him during your kind of education, Gregor Mendel and the pea plant experiments. I'm not, it does vaguely ring a bell, but please enlighten me. I think it actually is part of a lot of curriculums and probably it doesn't stand down because he was a monk. was an Austrian monk, think. And he was like really one of the first persons to really experiment with, ⁓ with plants, with pea plants more specifically. ⁓ and, and he's been called a little bit of the grounding father of genetics, ⁓ which is a field where I actually ended up doing my studies in. So I'm a bioscience engineer and I think he's one of the first pioneering bioscience engineers and why, he was in a monastery. was a monk. ⁓ they had a nice garden in the monastery and he was actually, ⁓ culturing pea, plants. small peas. and, he saw that there was some kind of variation in the plants. had plants with big. seeds, had plants with small seeds, you had plants with big leaves, smaller leaves, etc. And he was kind of interested, what if I cross these plants? What if I cross a plant with big bees and then big leaves? Would the offspring, would then the next generation also have big bees and big leaves? And he really documented this very well in his notes. And this is where the first time you can really see a very thoroughly executed scientific experiment. showing that from the parent generation, some traits are inherited by the offspring. Things like pea size, ⁓ petal size, maybe, I don't know the exact details. But when I learned about this, like, ⁓ this is like somebody that experimented with plants, with peas. You really found something that there is something inherited from parents to ⁓ do the offspring. At this point, nobody had a clue what it was and how it got, what actually the action was. And I think this was the first introduction into genetics, which then later on became DNA because then if you take a deeper dive into why do these properties get inherited from parents to offspring? Is it through some kind of fluid that goes from the mother plant to the baby plant, or is it because of some other molecules? And this is where they started to zoom in, like looking at They found that the nucleus, so one part of the cell is very, very important for that. Then they found out, ⁓ it's the chromosomes probably. And they took a deeper dive into the chromosomes. And then in the 1950s, 1960s, with the discovery, with the help of Rutherland Franklin and Watson and Crick, is really, really found that, ⁓ yeah, it's the DNA that's really the carrier of all of this genetic material that will go to the osprey. That's super interesting. So plants have DNA as well? Yes, everything has DLA that lives like from eukaryotes, from plants, animals, trees, flowers, whatever, ⁓ to microbes. ⁓ There was a certain point in my life where I was super confused about what had DNA and what didn't have DNA, but most of the living, all of the living things in life, they actually have some kind of DNA. And we can argue about one specific part of life, which are called viruses, ⁓ viruses that make you sick and whatever. They sometimes are RNA viruses. Whether they are living creatures. That's another discussion, but yeah, everything that lives, ⁓ is it has DNA. so would you say that having DNA is kind of mandatory in order to be alive? So that's an interesting discussion that, ⁓ lot of virologists will probably have some opinion on as well, but I do think I always, I used to give this kind of. presentations and I said, one of the taglines that I use is DNA, the basis of life. ⁓ So the base of life, I think that's true. think ⁓ for a creature to be able to have offspring, to go to the next generation, you need something where all of your traits, where actually it's a manual. It's a manual. DNA is a manual so that the next generation knows what to do. So yes, I think DNA and life is very, very significantly ⁓ connected, I do wonder what, what we can maybe find in outer space, whether there's something else, here at least on planet earth, ⁓ DNA and life are very much, ⁓ mixed together. Yeah. Yeah. So there aren't just evolutionary, yeah, evolutionary, ⁓ how would I describe it? ⁓ benefits to, having DNA. It's like, there is no. evolution, is no offspring without DNA because if there's no DNA, there's no information to be transferred onto the next generation. Exactly. Of course we're talking about biology and biology always has this very, very niche, everything is science, guess. there are exceptions to the rules, there's always something that maybe carries information on another carrier than DNA, but it is true. DNA is a very stable molecule. it is one of the things that ⁓ you can actually give to the next generation. ⁓ And this all boils down to something that's called in molecular biology called a central dogma of molecular biology. And that's basically if you think about the living thing, but if you zoom down onto the cell level, so we are all made of different cells. Plants are made of cells, trees are made of cells, bacteria are cells. If you really zoom down on the cell level, the things that actually do the work is what we call proteins. Proteins are the things that actually execute every daily task in the cell. But in order to make a protein, you need ⁓ some kind of manual, some kind of ground blueprint on what the protein should look like. And that is actually stored into DNA. And DNA is very well protected inside because if it's damaged, your original print is damaged, This will lead to mutations, which in human context will lead to cancer or other kinds of diseases. So you have to protect it. so DNA is very, very well protected. And in order for this blueprint to be read, you have some, another molecule called RNA, which has also been famously popularized by the mRNA vaccines. I mean, the COVID times, but RNA ⁓ is like the translational step between DNA and proteins. So we need all of these things in order for a living cell to work. But I think it starts with a DNA, which is a blueprint, but a cell with only DNA and no proteins wouldn't work. And a cell with only proteins and no DNA would probably just die off after a while and not be able to split and continue to grow in the future. If that makes sense. Yeah, no, it makes, it makes a lot of sense. And how does DNA store information? Because we all know what DNA looks like. can just. Look at your shirt. Everyone knows the famous ⁓ helix as they call it, I believe. ⁓ But how does that actually store information and also so efficiently because I believe DNA is incredibly small, but still it's able to encode all this information and is able to recognize if you just pull a hair out of my head. You may also be able to tell ⁓ what the color of my eyes is. Yes, that's an interesting question. It is a very dense format to store information, especially if you look into carriers that we nowadays use like hard drives or whatever. It is very dense. You can store a lot of information on a DNA molecule. How it became so efficient evolution, I guess, this is the one thing that actually it's a stable molecule. Maybe going back to the first part of your question, think that's important to answer first. It's how do you store information on DNA? How does that happen? And that's actually something very, very simple. You have four building blocks, are four nucleotides, as we call them, which are small molecules. And these molecules, they can actually be arranged in a way so that they are connected into a very long stream, which is what we call our DNA. And it's a stable molecule. doesn't break down naturally. If you compare this, for example, to RNA, which is a derivative, if you want to call it like that. This breaks down very, very, very easily. But DNA is like a very, very stable molecule. And I guess this is also one of the things why it's such a good information storage medium. But these four building blocks, they allow a lot of diversification because the four building blocks, they are the A, C, G and T. They have more official names, which I'm not going to say here, but these are the four molecules that the four building blocks, A, T and G, just one letter codes are easy to remember. And you can actually format these A, T and G in different orders, right? So you can have sequences like A, C, C, C or A, C, G, T, T, G, C, A. You can do whatever you want to. And if you think about that, that you have these four building blocks to play around with, This is basically all you need to have some kind of, it's like our alphabets, our alphabet is also just in random order. ⁓ So the, these, these different letters that you actually just put, that's a language, put off for each other in an order. ⁓ And if you mix the numbers, you have the letters, you have a different language. It's the same with DNA. ⁓ And also very, very, very, very much alike how we store computer data, which is just zeros and ones. It's binary. Here you have four building blocks allowing a bit more kind of information. ⁓ But yeah, that's actually the core story is you have these four building blocks that can be arranged in a different way so that you can store information on it. Now, what does this information mean? That has been a very, very, very big challenge. And I think this is also where technical revolution really kicked in in the 80s and 90s where we actually developed what we call the field of molecular biology. where you basically get some kind of research tools, lab tools to manipulate DNA, to amplify DNA, but also to read out the DNA. ⁓ And we have ⁓ something called like the first human genome ⁓ project, which was a big, huge project where one of the founding fathers also Craig Fender recently passed away, unfortunately, but the human genome project was all about if he can read out the DNA. We also understand what's going on in every human. Now, that's not true because we can now read out all the A, C, T's and G's, but what does this actually decode for and what does it mean? Which A, T's and G's actually code for hair color, for eye color and whatever, and all kinds of functions. That's still a very, very big ongoing quest where we have been able to decode a lot in the past decades. It stores information, but extracting that information is still a big challenge in biology and health and all kinds of sciences. Yeah. But isn't that what CRISPR is trying to achieve? So we have DNA and then we kind of isolate part of this DNA because we recognize that this part of the DNA is for example, responsible for the color of the hair or color of the eyes, or maybe even IQ or whatever. And then we try to modify that specific area of the DNA to maybe make someone immune to a certain disease or perhaps change the color of someone's hair. Or is that not true? No, it is definitely one of the most interesting tools in our toolsheds on figuring out what's going on with our DNA. Because if you think about the whole revolution ⁓ in the 80s, 90s, we could actually amplify DNA. So if you have a DNA sample, we could amplify it. And so we have more DNA, which is easy because it's just a small molecule. It's very hard to work with just one copy of DNA, let's just say. So you have then the ⁓ lab tools that could amplify DNA. I think the next generation of revolution is then reading out DNA. So that's actually trying to figure out what is the exact order of these DNAs. And then we have all of these methodologies that also allows to edit DNA. And I think this is where CRISPR-Cas is one of the oldest generation, newest generation. There were other methodologies before that as well to alter DNA. And ⁓ it also has been evolving into a therapeutic kind of application where you can actually use it needs to cure people or to change the specific characteristics in the future. But if you think about it as a basic research tool, you could actually use it in the lab. for example, in microbes, if you want to go into pea plants again, ⁓ just take out the part of DNA, alter it, grow your plant and see what it did. And by doing this in a large scale, for example, you can do this with microbes. There are very cool experiments in synthetic biology where you basically knock out every gene. if you maybe have like two dozen genes in a microbe, then you actually... with a methodology like CRISPR Cas or another molecular methodology, take one gene away and then see what happens. Is the microbe still alive? Is it still healthy? And you can do this at a large scale. We wouldn't do this on humans. It would take us quite a while and it's also very analytical, think. But this is indeed like a tool where if you edit something, see what happens. And then you, oh, this gene is probably involved in this function. And this is how we learn. This is how we figure out what's going on. ⁓ and so, so I would say, ⁓ Christopher, because it's a very interesting technology with also ⁓ a huge therapeutic avenue. ⁓ but it's especially in the early days, no, in, the lab where we can alter microbes, where we can alter, animals from small animals or maybe plants is where you really learn what the functions are of certain genes. Right. It's super interesting. ⁓ yeah, I'm planning to do a separate episode on eugenics pretty soon. I don't know ⁓ who the guest will be yet, but ⁓ it's a discussion for another day, but it's super interesting. DNA can also be useful ⁓ in crime scenes. If I spit on the floor or if I leave my hair somewhere, ⁓ investigators, people in the laboratory are able to tell that I was there. How does that work and how accurate is that? So I'm no expert in criminology and also ⁓ not an armchair detective, I would say. ⁓ it is crazy to think about if you think about like serial killers back in the day where we didn't have this technology. And I think one of the biggest technology advances are indeed in reading out DNA and being able to read out DNA relatively cheap. If you think about the price of reading out DNA of one human 10 years ago or 20 years ago compared to what it costs today, maybe a couple of hundred or hundred fifties compared to like thousands or millions of euros. ⁓ It allowed us like a serial killer back then wouldn't probably think about it. The fact that DNA is something a new technology could actually fix, read out and then link it to them. So how does it work? think we have DNA is pretty stable. Like I said, as well, we can actually still find DNA molecules everywhere. That's what people also do. They take samples of environment and they can figure out what microbes have been here, et cetera. So it's all about reading out. And then one thing that's of course, obvious, but also probably hard from a computational side of things is people share a big amount of DNA like me and you, have ⁓ our DNA is pretty much the same on a lot of ⁓ areas. Like we have a very, very big portion of sharedness. And so I think what people in this field do is try to figure out which regions of the DNA actually differ a lot between individuals. And these are maybe regions that code for, we can say skin color, can say hair color, eye color, or other kinds of things that are maybe hidden from the outside world. But these kind of regions, then you can actually then use them to trace back, oh, Sandra has a specific mutation in this gene. Okay, that's odd because maybe 95 % of the people in the world don't have that mutation. And I'm still a healthy person, but I have that specific letter that's different, which will not lead to any kind of different ⁓ properties, but is still in my DNA. And then they can start to trace back. So I think one of the things they did ⁓ in the context of crimes is then sample whole villages and try to figure out, we have some unique species of DNA who here in the village also matches this DNA. And it doesn't have to be the exact person yet. If maybe a relative, a father, a mother, nephew or whatever also has this mutation, we can start to trace back lineages and families and then go from there. So I think the first big thing is like reading out DNA. We saw a big revolution and then it's about finding these very, very specific mutations, differences that are, that are shaping individuals like you and me. Yeah. And you mentioned relatives there. are a lot of websites that you can send your DNA to and basically they'll analyze it for you and they'll see whether you have maybe some Roman blood or whether you're 6 % Chinese or whatever. How does that work? Like are those websites, are those services ⁓ legit? Like the bigger ones? ⁓ I'm curious to understand how that works. Yeah, it's been a while since I've been on one of these websites. So I don't know what the state of the art is nowadays, but I must admit that I also sequenced my genome just out of curiosity. There was also a specific mutation in my family that was maybe causing some kind of distress, especially ⁓ thinking about ⁓ my own family planning. that I wanted to check. ⁓ I also read out my genome and figured out what was going on there. And I also looked into them, what else can I do with this? And I think there are a couple of gimmicks that you can do. There's like basic reports that you can get. For example, I learned that I'm a very good caffeine metabolizer, meaning I can actually process caffeine pretty, pretty quickly. And this other kind of things that are like lifestyle related. Of course, there's also the really big health things that you can look into. For example, if you have cancer diseases in your family, there's a gene called the BRCA1 gene, or the Angelina Jolie gene, which is correlated with breast cancer. And so a lot of people that where you have a specific mutation in the gene, they are more prone to have breast cancer so they can take some preventive measures, for example. ⁓ But these kind of applications, the health applications, I think they have to go through clinical trials, they have to be tested, they have to be validated. That's something that's really thoroughly validated before we take some really health decisions on that. Then you have the lifestyle things, where maybe like I said, I'm a caffeine metabolizer or maybe a vitamin, whatever deficient kind of producers. I'm sometimes on the edge of these kinds of things. feel like there's also a lot of hype where you can actually then do these things and I figure out, ⁓ I need to buy these supplements because that's what I exactly need to, so that you have, ⁓ insights and then an action, is a cocktail of supplements that will give you a more healthier lifestyle. I'm not too sure about this. I'm, I'm, I'm sometimes skeptical about this as well. Although I know that in, in, in top sports, ⁓ these kinds of analysis are sometimes used to get better insights and maybe increase performance. ⁓ And then you have the things like what you said, finding relatives or what I did is ⁓ there's this website that allows you to find like, match your sample with ancient samples. So ancient graves that they found in history, for example, a Viking grave or whatever, or a Roman grave. I don't know whether that's actually true, but I know there are some kind of DNA sequences that exist ⁓ from ancient populations. And I kind of like that because what they then do is then try to match your DNA, whether you match with any of these kinds of populations. And that's how my wife discovered that she has Viking heritage. she always uses that like that. was just going to ask, you a Viking? I'm very boring. I'm very much like, live in Belgium and I have like a big match with the Frank DNA. So the tribes in the German kind of areas. So. So it's actually pretty normal. I didn't kind of discover any kind of family history secret, et cetera. And I'm also not too sure how to really trust this in depth because of course there's just one sample that you match with and how much percent of a match is like a real match. These are still, I think ongoing questions, but interesting nevertheless. And then you have the whole application of finding siblings, lost family, tracing back people. I think that works. ⁓ Definitely works. You only have to have a match with a far cousin to find them. Whether you want to do that, I think that's a very personal decision that you have to make yourself. ⁓ But yeah, technically I think it all makes sense to do. Yeah. And are these matches that we're currently talking about, that just like, we see that a large portion bigger than, I mean, of course every human has? is going to have similar looking DNA and some things might be identical. But when we're talking about relatives that an even bigger portion of the DNA, the A, C, G and T sequences overlap so much so that the only conclusion that can be logically drawn is that you are related to someone. Yes. So it's all about statistics. So they probably put numbers on it. I never used one of these. ⁓ services, but I can imagine that there comes some kind of statistical power and statistical kind of measure that shows you how certain you can be of this kind of match. And I think it's all about looking like at specific letters. Indeed, like what they typically do is not match the whole DNA, the whole genome. What they typically do is look at hotspots, like small areas that are variable between different populations, between different people. And the more overlap you have in these unique mutations. the more mutations that you have very specific with one person, I guess the more related you are. Now that's the science, these companies actually, or services actually implement this. No clue. I can only say that you probably have to go and figure out and find evidence of who's behind this kind of company and this service because I think it can also be very badly implemented and give you false positives if you do it wrongly. at least with thinking from it from a scientific perspective, I think there is some kind of degree where you can really match people relatively easy with a big database and be relatively sure that these people are connected to us. Right. And how much do we know about DNA? Do we have DNA completely figured out or is there so much more that we would like to know about it? What's the level of science there? So one of my favorite podcasts, the Nerdland podcast, the Belgian podcast, there's a running joke there that every in the podcast they talk about science news and there's a running joke that every of a couple of two or three years, there's a new paper saying that they finished the human genome, that they finally read out all of the ACDs of the human. So we can trace this back to maybe 20 years ago, where like the first human genome was published. But yeah, what's a human genome? Human genome, is that your genome? Is it my genome? Is that an African and Asian genome? ⁓ So what's the genome? There's a lot of difference in there as well. ⁓ So I At this point, we just had the first draft and then we started to generate more data, more data, seeing what averages are, what places are different. And then there's also the areas that were hard to read out. Some kind of technological limitations limited us to read out certain regions that are, for example, have a lot of repetition, A, C, Cs, and Gs after each other. So C, C, C, C, C, C, C, or G, G, G, G, These kind of methodologies, they flicked and they weren't able to fully capture these regions. And so we saw some new innovations in that regard and that led to new papers and publications saying, ⁓ now we finished the genome. So that's one thing. It's about reading the genome. That's the first thing. Understanding the genome and then thirdly, editing the genome are of course the other outstanding challenges. So let's assume that we finished out reading the genome. Now it's also about understanding. We don't understand. what every letter codes for. And if we do, if we understand that this specific letter codes, codes for a certain protein, for example, we often don't how, what the importance of that protein is or how well it is connected or what happens if we actually shut down that protein. What is the effect on your health ⁓ on just as a living organism? ⁓ So I think understanding the genome is something that we um, do from taking, doing experiments in the lab and then translating it and figuring out what it does to humans. And that's all bioinformatics. That's all like, oh yeah, we have a very similar organisms or we find this gene also in a microbe. It probably does as the same or a similar function in humans. Um, but that's not always true. Maybe there are some differences, et cetera. So I think fully understanding what the human genome actually fully encodes is still an ongoing challenge. Maybe we can, there's a new generation of AI machine learning tools that can help us understand better things. So definitely. And then the third, what's next for DNA is of course, like what we've already been doing for a while. And it's also the call of the field of synthetic biology. We can alter DNA relatively easy in labs. And we're doing that very frequently on microbes, on plants, and then figure maybe create new things. For example, famously insulin. ⁓ It's a drug for diabetes patients. It's being produced by microbially engineered microbes. So you take the DNA of the microbe, you put the gene of insulin in there and it starts to create insulin, which you then can use as a medicine. So this is, it has implications far more further than just health application in humans. But then of course, yeah, the big question is how much would we allow in transition of editing humans and what are the ethical effects of that? and you mentioned eugenics, how will we go about that? How will we, ⁓ what will we allow? Will we be, will we edit, ⁓ in yeah, embryos will we edit humans, whatever. ⁓ it might make sense from an ethical point of view. If somebody has a, ⁓ a DNA disease that that's horrible. I know somebody who's really suffering from, from, from Huntington diseases. Yeah, it's a terrible disease. If you can fix that by. altering the genetic material of patients there, it will probably have a good effect. But what if you allow people to choose the color of their eyes? What does that bring to society? These are outstanding questions, I think, no, questions that need to be answered. And I'm also not fully, fully, ⁓ on the stone, decided on what's next there, I guess. No, it is a very difficult topic. mean, I think that most people would agree that if we can edit the tomato plants to be more resilient to cold weather or warm weather so we can have more juicy tomatoes for a better price. I think there aren't many people who are going to say that's a plain God, right? You're playing golf for the tomato plant. Whereas if you start to, to edit humans, it's a different, different conversation. had Anders. Sandberg on the, on the pod the other day, ⁓ he's a trans humanist, and he believes in the total freedom for humans to modify their own bodies, whether mechanically or biologically, because he argues in a sense we're already doing it. For example, when we, vaccinate someone, ⁓ becoming sick is part of nature. And by vaccinating someone, we are editing this person in a way. that already isn't natural. He believes there shouldn't be any limits to what we do. But of course, ⁓ that's, I think not the position that most people have. think most people sit somewhere in the middle. ⁓ And then where you draw the line depends maybe on your religion or maybe it depends on your values. But yeah, I can see there being a difference between eliminating nasty diseases ⁓ and that there's a difference between just improving someone's aesthetics or changing someone's aesthetics. ⁓ But maybe sometimes they go hand in hand. Maybe if you can become a little more muscular to combat ⁓ elder, ⁓ if you become older, you become less mobile. So by improving someone's ⁓ muscles, they can live longer, for example. That may also improve the way they look. yeah, it's not an easy discussion for sure. No, no. And you're very right that different society, different kind of cultures will have different views on this. But I think it's, it's interesting that you very casually started this, this common by saying like, I don't think a lot of people will probably ⁓ find it wrong if you edit a tomato to be more resilient, but that's exactly what was like the big, a huge problem in maybe 20 years ago. I'm not sure what the current policy is, but for example, the European Union, they have banned for a very long time GMOs, genetically modified organisms. Everything that comes up in the food chain in Europe is by definition treated as hazardous. I'm not sure what the current policy and views are, but not even five to 10 years ago, eating something that was genetically modified was seen as a very, very big danger. ⁓ so I'm not sure how ready we are for the human editing and, I get there, every point of the, on the spectrum can have some pros and cons in that. And I think we have to, be careful of what it opens for society in the future. But you're, yeah, something sensitive about just what kind of food and specifically editing something in there already triggered huge discussions. And now we're, maybe X years further and we're discussing about what it might do to humans and not only about curing, but maybe also about changing something that you personally like. And yeah, that's interesting. Let's see where this goes. And I'm not sure what my current stance on this is at the moment, actually. No, you don't have to pick a position now, I heard an example for example. That they were, ⁓ NASA is pro is I believe investigating whether they can, ⁓ genetically modify their astronauts to make them more resilient to radiation. So of course, when you go into, into space, ⁓ especially with the plan trips to the moon, they will be exposed to. copious amounts of radiation because there is no I mean the moon is still somewhat in the magnetic magnetic field I guess but there's a lot more radiation there than there is ⁓ here on earth so that's what I heard but it might yeah I think they were investigating it and and probably not already doing it ⁓ but one thing I really wanted to touch on today as well, ⁓ is something we, ⁓ discussed last time. And that is the possibility of using DNA as a storage device. And, ⁓ you had a very, very cool introduction to that topic by competing and winning the Davos Bitcoin challenge quite a while back. ⁓ for the people that have no idea what I'm talking about, can you maybe explain what the challenge and tilt and, ⁓ yeah, how you ended up winning it? Yeah, of course. know this is a podcast is an audio format. But what I can describe you is I'm holding a tube here, which contains a micro drop, drop that of DNA. Basically it is from, from, ⁓ the Dave has Bitcoin challenge. It's a, it's, it's, it's a small too, basically a very, very small tube with maybe two or three droplets of DNA in there. And this whole story actually started with a proof of concept 10 to 15 years ago where they said like, hey, DNA is the basis of life. DNA stores a lot of information like you already said, it's very dense. We store information on other kinds of media, like we used to store it on CD-ROMs, on floppy disks, on whatever, on tape, and nowadays on hard drives. And there's a lot of similarity because if we store a computer file on a computer on a digital system, it's usually a long string of zeros and ones. It's binary, it's coded. If you trace back any kind of file can be traced back to like a binary zeros and ones. And then you have this concept of DNA that uses ACTs and Gs. So it has like a four base encoding instead of like zeros and ones to binary. This is like four bases that you can use. So in In it's relatively easy to translate the strings of 0s and 1s to a string of A, C, T's and G's. So virtually on a computer, it's just about writing a very short algorithm. So let's say every 0, 0 will code for an A, every 0, 1 will code for a C, every 1, 0 codes for a G, and every 1, 1 codes for a T. So then... That's basically like a dictionary. You translate it, your string of computer file into a string of ACTs and Gs. But then at that time, there was the idea like, Hey, what if we can physically print this? What if we can now really print this on a physical medium? We can spread it out and then people can then actually take one of these tubes and read them out. and then, then restore the original file. ⁓ and that's exactly what, what Nick Goldman did Nick Goldman from the European bioinformatics institutes. I already knew this guy from my research work. He did a lot of work in phylogenetics. So how bacteria are related to each other. And he posted on Twitter something back in the day when I think I thought Twitter was a nice place to be. There was this scientific community and he posted like, Hey, we have this paper where we show a proof of concept that it's physically possible to translate zeros and ones into HCT's and G's, send them out to a specialized company that can really print this into a physical molecule like they use a printer, which is a ⁓ big technological advances that also just came in the last decades, a printer to physically print these ACTs and Gs that you give them. So you go from zeros and one to a computer file with ACTs and Gs, you give it to a specialized company that will print it out. And now I have a tube with a file stored on physical DNA. And then one of the things he put on Twitter was like, Hey, we launched a challenge two, three years ago in the world economy forum, because this new concept of storing data on DNA was a big new thing. I was invited to give a talk into the audience and he really distributed this physical tubes actually to the audience and said like, Hey, the first one that can decode it will find a nice surprise. They will find a Bitcoin stored in this sample. ⁓ ⁓ I think he bought it for like maybe 100 or 200 pounds. ⁓ so there was like early days, ⁓ he was, he was kind of looking ahead already. And it put it on Twitter and said like, Hey, ⁓ in a couple of ⁓ months, this challenge will end because we, opened it for three years and we are now two years, there may be nine months further and nobody has cracked the code. There's multiple reasons for that. people that got the tubes, I guess people in Davos, it wasn't me there. There were like world political leaders and whatever. They probably didn't have the knowledge to do that. But I answered on this Twitter message and I said, like, Hey, can, can I get a tube? doing research into microbes and DNA of microbes. I'm a bioinformatician. So I know how to work with biological data on my computer. Is it possible to get get a tube and he said, yeah, fine. If you give me a motivation letter and what you're going to do, I'm happy to send one. So I was pretty chachi PT. So I had to come up with my own motivation letter, of course, and send it out. And I think he liked it. He sent out the tube to me. ⁓ that was back in the day at the university of Antwerp in Belgium. And I had access in the lab to, ⁓ to the machinery to read out DNA, so-called DNA sequencers. I had to go all the way across the university to do that. But so we got a tube physically. I was like, okay, now I need to read out the DNA, which also comes through the law of challenges because back in the day it wasn't, yeah, probably today as well. You still need to do multiple steps and I wasn't too sure whether I was doing the right thing. But in the end, I was able to get a computer file with ACTs and Gs, a long computer file. And then I really needed to solve a puzzle because I'm explaining it very simply. You have zeros and ones that you can translate to A, C, T's and G's, but there's a lot of algorithms coming from the information technology, from how we, for example, send radio signals and you send it out on a certain frequency, your radio receives it and decodes it back into audio. These kind of tricks, they also had to implement to make sure that if there's something wrong with the printing and the reading of the DNA, you still have enough information to recover the original pattern. And so basically I had to write all kinds of algorithms myself on the computer to really then decode it and figure out what's stored in this file. I did this with a colleague at a certain time because I usually code in a language called R at that time and it wasn't really working, really working. So I went out to another colleague and I had a small hackathon at a certain point. And this is where we really were like, ⁓ that's, ⁓ he made my strips so much faster. didn't work back then. Then when I was cycling home and I was like, Hey, what I'm doing is I'm actually just using like, let's say two or 3 % of the data, because I think most of the data were rubbish from my own work. was like, if I see DNA being read out with a certain score. I think it's not valuable. So I was cycling on and I said like, one last thing I'm going to try. And this was maybe one month before the challenge was closing. It was closing in February and it was January and I was like, maybe I should just run the whole thing again on my, all of the data instead of just this best proportion. And this is what I did before I went to bed on a Saturday evening. I just opened my laptop. said, just do it on everything. And following morning, had to go and play volleyball. I played an amateur volleyball team on Sunday morning. I was like, Hey, what's this? It actually finished without any kind of errors. And previously it's always finished with errors. And this is where I saw like, Hey, there's a message here. And the message is that like, congratulations, you did go to the Davos Bitcoin challenge. Here's a key to the wallet. If you use this key, you can actually ⁓ pull in the Bitcoin yourself to your own wallet, which serves as a proof that you were able to actually decode this physical sample. And so, yeah, that's what I did immediately. And I actually sent an email ⁓ to Nick saying like, I think I cracked your code, here's some evidence. And he immediately phoned me and said, is this true? Did you actually? And he was amazed. There were some other gimmicks in there. So there was a Bitcoin, but there was also like a a drawing of James Joyce, is ⁓ Nick's father used to be a James Joyce scholar. So it was interesting to pick around and solve a puzzle and figure out what else was in there. It was kind of a surprise to me. And of course, a very nice present at the time. Yeah, because at the time that he put the Bitcoin wallet in there or the Bitcoin in the wallet that he encrypted in there, I believe it was only a couple hundred dollars. But in the meantime, because the challenge was just dormant for many years, by the time you opened it, the value had skyrocketed. Maybe not so much as it is today, but it was a lot more in value. How much was it when you decoded it again? So this was the exercise I did before starting. For me, of course, it was super interesting to just do the scientific challenge. Like this from a scientific perspective. doing this kind of research and this kind of detective work was awesome. Like it's really, really, really state of the art. So that was the first trigger point. But then the second trigger point was like, of course I need to make expenses in the lab because sequencing, it kind of costs money. It still costs a lot of money. It's not something I could pay out of my own pocket. So I was like, what's the cost benefits analysis here? I was also a PhD student. didn't have that big amount of wealth. So I was like, yeah, let's do the calculation here. And so at this time period, one Bitcoin was around 8,000 euros, 7,000 to 8,000 euros, which made sense if I would really deduct the wet light cost I had was right. A thousand to 2,000 euros. I was like, yeah, this makes sense to try out. Fortunately, I also got sponsored for this, but at this time it was 8, 9,000 euros, or 7, 8,000 euros, I think. And I was just... so happy with the fact that I could physically transport it and I wasn't ⁓ a long time believer of cryptocurrency. I did have some ⁓ past experience with that. I was like, yeah, whatever. ⁓ I'm just going to go on a holiday with this. And I booked a holiday to Peru with my wife. I actually throw a big party for the end of my PhD where I actually treated all of my colleagues with an extra, a nice dinner. ⁓ And I guess that's where the fun ended already. And of course, if I look back at it, it's like, yeah, unfortunate. I could probably find it as a part of my house instead of just flying to Peru for a summer. But the whole experience just brought me so much joy that the value was high enough, was significantly from 200 euros, to 8,000 euros, which is a significant raise. And that was enough for me to just get started. Yeah, but I mean, might sound cliche, but that whole experience and that whole challenge, mean, that's you can't really put that into any, any monetary, you can't really put any monetary value on that because I remember it still, was, it was all over the news. was huge news. And I think rightfully so because it's so incredibly interesting to me that we can store digital information into this biological format and then also retrieve it back onto this digital format again. So I think that's really cool. Why aren't we seeing more of this? What's the current state of using DNA as a storage device? Because it is my understanding that DNA stays Well, for an incredibly long amount of time, I believe we have successfully extracted mammoth DNA. I believe DNA doesn't even have to be ⁓ cooled as much as regular data centers and whatever you want to call it. So why aren't we seeing more of DNA storage or is that ⁓ on its way? That's also a very interesting question. I think it's all about bridging the gap between valorization. So I run my own company now, ImmuneWatch, which is basically also taking something that was discovered at the university and then building a business out of this or making sure it actually translates into useful applications. And I think what we're seeing here is like a very cool from a scientific point of view, or like you're saying on the fundamental level, it's interesting because we can store DNA for a very, very long time. But it really, really extends far more than the human lifetime. But of course, we're also humans and we also tend to think on a very short term. So what is the most practical, useful application of storing something for a very long time that even goes beyond our own lifespan? What is the killer application that we maybe want to pay money for now? in a research context, ⁓ what is so valuable to actually do that effort and then ⁓ get somebody or some instances to pay for actually. And I think this is the challenge that maybe is being solved or that we're trying to solve. Back in the day, of course, there were some thinkings of like storing ⁓ information that has to be stored for a long time. For example, You should think about huge experiments that people do in the large hydrogen colliders, this kind of like in CERN, where they have a lot of data that they cannot analyze at this point, maybe it's cheaper to then print it on DNA, store it for a very cheap time. Because yeah, one of the advantages is you don't have to have big infrastructure. If you think about storing our own data now in hard drives, we need really big data centers, we need cooling, we need electricity. You need to actively do something to store the DNA. While DNA, can be, no, sorry, to store computer files, while DNA can be maybe a bit more passively. So the first application they were thinking of, what if there's huge chunks of data that we know we don't have the compute power to analyze now? What if we just take it out of a compute system and store it on a more passive medium, a medium that doesn't require this kind of intense energy, and then DNA could be a solution. ⁓ I also know that there was a new generation of startups in this game as well. ⁓ For example, France, where they also tried to, ⁓ where you could actually store some mini information on DNA that gets sent physically to you on a card. But I'm not sure what the next killer application would be. Unless if you can think about, yeah, because we're very data hungry. If you think about the LLMs and all this, we need data, we need it now. We need it accessible now. There's a huge lag time if you actually store data on the physical tube that you physically have to go and print, store somewhere, retrieve the tube, then sequence it decoded. That probably takes a couple of days instead of now just microseconds on something that is stored on a data center on the other side of the world. So I guess we have to probably look into applications that allow for lag time, but are important enough to store for a long, long time. And that makes sense. I'm not 100 % sure what the new killer application and I do hope to see something, but I'm not at the cutting edge anymore of that to see where maybe the pioneers are trying to come up with a new interesting application. Right. No, I understand, but maybe something like national archives or something. know for example, that in the Netherlands we have is huge archive that stores all of the television we have ever broadcasted. ⁓ which of course is, yeah, is growing every, every single day. ⁓ so yeah, I assume that that is that something we need readily available or is that something that maybe, Hey, we want to request this, this videotape from, from 1956 on, Wednesday. Like it's probably not something that people need every single day. And it's probably something that if they do need it, they, they won't need it now or, or, ⁓ it's very urgent. It's a very interesting use case, but I do want to challenge on that and figure out like, how do they currently store it? I don't think they have digitalized the whole library already. Right. Or are they doing this? I think this probably are still physical tapes. ⁓ and, and, and the effort of going through a whole library, it costs. You need employees to do that and our people to do that. You need probably a bunch of, because you really have to physically take it all to tape and then find a machine that can translate this individual information and then you need storage space. So maybe it's sometimes better to just leave it as it is. then, but you're right, it could be an application, but I think it's also a big hurdle to get started with that. And we need some pioneers to do this kind of first killer application where it makes, I think. economically sense or maybe not first economically sense, maybe it should also just approve of concept and then later it becomes economically sensible to translate the whole catalog into DNA. you're right. Yeah. And what I read somewhere, I don't know if it's true, but, ⁓ that one of the problems with using DNA as a storage device is also that if we want to read our hard drives and just open a photo, for example, let's say we have a thousand holiday photos and we just want to open the one. We can just go to that file and open one photo, look at the photo, close the photo and shut down the hard drive again. But it is my understanding that with DNA, need to read the entire thing. so that's also kind of impractical if you just are looking for one single file and then you need to open like how many terabytes you have stored in there. Yeah, that's interesting. I do think there were some kind of innovation in that regard where, you basically can have smart technologies, not digital technologies, but where you have technologies that were, can on a molecular level, ⁓ only amplify or only read out a certain parts that you may be tagged with a, with a certain tag and then. first use methodologies to maybe using CRISPR, don't know, and then just really focus on that specific tag, filter that out and then only read that out. So I think what you're saying was probably two, 10, 15 years ago, but I do think there were some innovations that allowed to retrieve specific pieces of information from a big set. So I do think people are still innovating in this space and maybe that will lead to a new application that we can't even think of today. So I'm not sure it's completely true to this day. Okay. Well, if it isn't, it means they're still working on it and advancements are still being made there. ⁓ think finally, ⁓ I was also interested in ⁓ your current company and what you do at Immune Watch. Can you maybe talk a little bit more about that? Yeah, it's interesting. So on LinkedIn, also write that DNA. think that people underestimate what people can do with DNA. And if you think about my my own career, then, um, from an outsider, it really looks that I've been doing random things after each other. But I think one of the, one of the things piecing it together is definitely the DNA molecule. Uh, so I actually started my career in bioscience engineering. So I was editing microbes in the lab during my master thesis, that's DNA editing. I then went out to actually study fermented foods, things like kimchi and carrot juice fermentations. I actually. worked with Michelin star restaurant chefs that were fermenting their own foods with microbes. And my job was like, Hey, what if I can take a DNA sample of your ferments? I can then read out the DNA and then use my computer to actually link or figure out what the original bacterium was, what was in there and how do they evolve over time, et cetera. So I use DNA methodologies to study fermented vegetable foods. I then went out to do a postdoc at the EMBL in Heidelberg. ⁓ where I actually studied the human microbiome. So that that's the collection of bacteria, ⁓ and, and, and other organisms in your guts. And I was looking at what is the influence of drugs, common drugs, ⁓ so medicine on your microbiome composition. And again, I use DNA technologies to see what bacteria are in there and how do they shift in the future. And this is a, after some academic career doing a master's PhD postdoc, I wanted to do something more entrepreneurial. And this is where I actually went back to my original university in Antwerp and started working with people that were using DNA to read out the immune system. You already said this before in the podcast that you were in the previous episode, talk with somebody about vaccines modifying the immune system. That's exactly the kind of thing that we are looking at. DNA is something very stable, but if you look at your immune cells, they actually change a lot over your life. And if you have two identical twins, that have the exact same DNA or almost same DNA and you put them aside, they will still have the same DNA after 20, 30 years, 40 years. But if you look at their immune system, this would probably be very much shaped by the environment. And this can be things like vaccine programs, but this could be things like natural infections, like sexual diseases that they had or whatever. There's all kinds of environmental factors that will influence your immune ⁓ system. And this is exactly what we're working at with ImmuWatch, where we actually help pharma and biotech companies that are reading out the immune system. We have machine learning algorithms that can translate the DNA readouts into really insights and figuring out what the immune system is currently attacking, whether it's attacking a cancer cell, whether it's attacking a virus, whether it's attacking a bacterium. That's the kind of insights that we are looking for. And it actually is a nice... way back to what we were discussing about DNA. We know a lot about reading our DNA. We know from a lot of parts of the DNA what is the exact function of the gene. But in the immune system, it's still a hard, hard challenge. We can see that there are certain immune cells that are doing something, but exactly what they are attacking, that's the kind of innovative machine learning approaches that we are bringing into the whole equation. Super interesting. And getting that knowledge of what the immune system is currently doing, what it's currently working on. Maybe it's a dumb question, why is that valuable to clients? There's a whole range of application that we can talk and look into. For example, you could use it as a diagnostic. You could use it really to figure out. what the immune system is currently battling. So this could be very valuable information to see what kind of disease somebody has, maybe very early cancer detection. That's future work. That's not something we're currently doing, but you could also use it for therapeutic design. For example, the whole ⁓ field of mRNA vaccines is also driven by cancer vaccines, where we develop specific vaccines specifically for your tumor, for your cancer. And in that sense, it's very interesting to them. administer a vaccine and figure out which part of the vaccine now actually triggered a good immune response, which part of the vaccine is actually curing somebody. And if you can close that feedback loop, that's what we are doing. You can actually go back and design better vaccines in the future. So that's in the therapeutic field. But most of the use cases we work on now is actually figuring out what the immune response is. So if you go into early clinical trial, And that's the real value that we can bring now. If you go into early clinical trial with a new cancer therapy, it's sometimes really hard to know whether it's really worked yes or no. And that's the kind of insights that we use. take samples before the therapy and after the therapy. And then we see how the immune system evolves. And then also more specifically, whether we find some specific immune cells that are really triggered by the therapy, showing some early indication that the therapy that they're working on is effectively effective. And that's the kind of insight that they're now looking for. Wow. Super interesting. Well, maybe, maybe we should do an entire episode on the immune system in the, future. ⁓ thank you so much, Sander. Is there anything, ⁓ we missed or anything that is still cool to mention about DNA before we wrap it up today? So, one thing that I thought about was, ⁓ the whole DNA field and life. It's very much connected. Like you said, We basically think about DNA as a basis of life. We talked about engineering organisms, about engineering people. We talked about storing something on DNA, which is then decoupled from life. And I think this is also an interesting area of application. know back from my days, and this must be more than 10 years ago, at university, there was a professor showing applications of DNA where they actually created physical smileys from DNA. basically create a DNA sequence that if you actually release it and print it, it will fold itself and it will actually look like a smiley. Like if you really look at it with a microscope, you will see a smiley there. And it's called aptamers. And I think that's also interesting. It's like you use this molecule that we ⁓ inherently ⁓ link with life to then create something new and a smiley is something stupid. But that's the first clue of concept, I guess. ⁓ and, this is also where research was going, like, can we not maybe make some kind of, ⁓ lock, ⁓ like a box with a lock on out of DNA? And what if we can then put a drug on a drug in the box? So make a physical box out of DNA that folds itself, put a drug in there, lock it up, and then actually put it in, in the human body. And it only opens as soon as it's in the right organ. For example, there are some kind of cells. in a certain organ, have specific receptors or specific molecules on the outside of the cell so that the box knows, ⁓ now I'm in the liver. Maybe I should open up so that you have a very local delivery of a drug in a local space. I've not been following this field, but I do think this is also a very interesting application of taking like DNA storage and like making physical things with DNA. I think this is interesting to see how we have a... It's really bioengineering, right? We take something that live evolved into a whole new area of applications. so, so that also kind of excited me. That's incredible. What's, what's this called? it, does this have a specific term? Yeah, I think, I think it's called Aptamir. So ⁓ Aptamir and, and, and, and I can send you a link on later on that we can show that as well. The specific image I have in mind of a smiley, it really, it really is cool to see. I'll send it over. And yeah, exactly. Now that you mentioned it, it does ring a bell. believe I've seen something similar like that, but it sounds like a very, very interesting, yeah, technology and use case as well. So something I'll definitely look into. where, where can people go? ⁓ Sondre, if they want to keep up with, ⁓ what you're doing, I know you're pretty active on, on LinkedIn and post some, some, some fun stuff there. there any more channels, ⁓ I, ⁓ should link or, or you want to shout out? No, for my own personal health, actually start not using any kind of other social media anymore. And so I think the way to go is ⁓ find me on LinkedIn. can just Google my name or ⁓ search my name on LinkedIn and you'll find me with a DNA molecule symbol added to my name. So it's easy to recognize me. I usually post about things from the business side of things, but I'm happy to reach out there. Um, or maybe you can take the context from there, but LinkedIn is the place to be for me now, um, as a, as a CEO of of a startup. That's the reality today. I think that's a very healthy, a healthy decision. Well, uh, thank you. Thank you so much, Sander. I, I really appreciate you. And, this was a very, uh, very cool. I've learned a lot and, yeah, we should do it again sometime. Uh, if we, uh, uh, I feel like there's a lot more we can discuss. Well, happy to be here. Also happy to make place for other people. Thank you so much for this opportunity and maybe see you in the future.