Kian Sadeghi: Consumer Genomics for Longevity, Future of health, Wearable Data Integration

Welcome to the Silicon Fox Podcast, where we explore the habits and stories of high performers. Join us as we dive into their journeys, analyze live blood tests, and break down the science behind key biomarkers to help you optimize your health. I'm your host, Mitchell Eschner, an ex-pro soccer player, a current sponsored hybrid athlete, a health tech founder, and a longevity enthusiast. Awesome. Well, Kian, thank you so much for hopping on the Silicon Fox Podcast.

Absolutely. Happy to be here.

I got a lot of spicy questions for you, but definitely want to just kind of prime the audience with a little bit about your background. Just give us the quick kind of who are you, what are you building, and we'll jump into some of the fun stuff.

Yeah, my name is Kian. I'm the founder and CEO of a company called Nucleogenomics. We're the world's most advanced DNA health test and analysis. We help patients basically live longer and healthier lives and also help Have healthy children. I'm a first-generation American. Both my parents are Persians. They actually escaped Iran during the revolution, came to America, specifically Brooklyn, where I'm from. Unfortunately, the story of Nucleus begins with a personal tragedy. My cousin, she actually went to sleep one day and she didn't wake up. She died in her sleep. She had a rare condition that causes irregular heartbeat, caused sudden death, and so she passed away in her sleep. And I asked my dad at the time, who's a physician, I said, how does this happen? He said, oh, bad genetics. I said to him, you know, what does that mean? He eventually, you know, I don't know. He said, you know, he just kind of shrugged his shoulders. And I said, okay, well, you know, I need to go like, I need to, I need to study this genetics thing basically. And so eventually I realized that disease isn't really an inherent property of human beings, but can be viewed more as a problem to be solved. If you could actually correct for the error that causes disease, you could well, you know, cure disease. And so I actually joined one of the first do-it-yourself gene laboratories in the country where we engineered yeast to make them eliminate, we added bacteria to make them resistant antibiotics. And I kind of, you know, loved the sort of beauty and depth of biology, but it wasn't very iterable. And so I wanted to, you know, combine sort of data ability of programming with this kind of depth of biology. And so I studied computational biology at Penn. After a year and a half, I actually saw the decreasing cost of sequencing a human genome. So it used to be a billion dollars to read the 1,000-page book that is your DNA. And then I saw in 2020 it was about, you know, $1,000. So a billion dollars to read 1,000 pages to $1,000 to read 1,000 pages. We all know where that trend's going, to zero. Yep. And so, I figured, okay, well, someone needs to build the application layer for DNA. I said, why not me? And, that was the grand illusion at the time. And so, I dropped out, went back into my bedroom in Brooklyn, lied to my parents, sorry, Mom and Dad, about what I was actually doing. I told them I was in a lab or working in a lab. I wasn't. I was working in a nucleus. Spent a year building around 18 subject notebooks and Realized I could build basically, as mentioned, the world's most advanced DNA health test, the most comprehensive assessment of some genetic risk for diseases and traits that's ever been available. And my parents said, okay, we're going to kick you out of the home. That was the reward for figuring that out. And then I said, okay, that's not good. I have to figure out how to raise money. And so, I cold texted an angel investor who invested, thank God, $200,000. And that's how Nucleus got started. And since then, I think we've done Well, pretty tremendously. I mean, I'm sure people have seen our recent announcements, so we're doing well.

Amazing, amazing. I love it. I'm sure we'll jump into some of the stuff you guys have talked about recently. But, on just a high level, why do genetics actually matter? They exist. There's not much that we can do to change them. And, you might be one of the best people to answer this kind of question. Why is this something we should care the same way I wear my Whoop, I wear my Oura, I track my sleep? Why Why should I start tracking my genetics?

Well, for starters, I think my cousin's a great example. I mean, she died because of bad genetics. And, you would think that's actually a more extreme case, but there are still millions of people in the world with severe genetic conditions. But, even if you're not one of those people, it turns out genetics actually impacts, literally speaking, every chronic disease you've heard of. So, let's take a step back and let's ask ourselves, what is the objective of the broader longevity and health movement? Well, it's to live as long and healthy as possible. And so, if you look at the longevity charts, you could see that between 1880, life expectancy was about 40 years, 4-0, and then in 2024, it was about 80 years. So, in other words, life expectancy actually doubled in about 150 years. Why did it double? It doubled because of a whole host of different innovations, including vaccinations, including antibiotics, including sanitation, and various other technologies. In other words, technology drives forward people living longer and healthier lives. What was the number one cause of death in people in 1880? It was bacterial infection. More than 50% of people died of bacterial infection. That was until you had the rise of antibiotics. Today, what kills more than 50% of people? Chronic disease, right?

Right.

You can Whoop track all you want, you're likely to die of cancer. Of diabetes, of Alzheimer's. You're likely to die of basically chronic conditions that is influenced by both environmental but of course also genetic factors. And, that's where genetics really comes in. If you want to basically live as long a healthy life as possible and then you look at what's killing people, which is cancers, heart disease, diabetes, et cetera, Alzheimer's, these conditions are actually by and large at least up to Like 50% or even more genetic. And so genetics is the foundation of your health. It tells you everything from your risk for Alzheimer's or your risk for diabetes and all the ways to cancer. And you might ask, okay, well sure, but once I have that information, what do I do? And there's many things you can do. You know, in my cousin's case, you know, she would've taken a beta blocker, which would've reduced her risk of dying by 10x. We didn't know, so you can't take the drug. If you're Angelina Jolie and you had a BRCA marker or breast cancer marker, Angelina Jolie is a famous actress. She's very famous for having a pathogenic marker in her DNA that increased her risk for breast cancer. She then got a double mastectomy that basically reduced her risk down to nothing for breast cancer, from maybe 90% to almost zero. You can get earlier, more aggressive screening in the case that you have a colorectal cancer variant, which is almost certainly to save your life. If you're talking about something like heart disease, sometimes a patient finds that they have really high cholesterol And you hear the same story again and again. They say, I have high cholesterol, but I eat right, I exercise, I do everything right, Kian, what's going on? Turns out they have a genetic marker or disposition to heart disease, to high cholesterol. And they know, okay, well, for me, given my genetic composition, I know that lifestyle and diet is not gonna change it. I actually need to do— I need to take a statin, for example, right? So that's a very great example of personalized medicine where you use a genetic contribution of your risk to different things to actually inform ultimately, okay, hey, I actually need to take a drug in that case. There are many more examples of this. I mean, I have a high genetic risk for schizophrenia. I'm in the 99th percentile. I've personally never done any drugs, but I know given my genetic disposition, I should really avoid psychedelics. I'm also a carrier for cystic fibrosis, which is a genetic marker that could, if my partner is also a carrier for it, dramatically increase my risk of passing down a disease to my child. It's of paramount importance that I would also screen my partner when having children. And, that's another great application of genetics where you can actually from the same diagnostic test avoid passing down a severe disease. I'm sorry, I'm going on a tangent here. My point is there's so many different ways that you can use genetics to not just help yourself but also help your future children.

Yeah. I mean, that's the big part of a lot of the wearables or stuff in the health space is the now what. And, it's interesting. I mean, that was my next question. You stole it out of my mouth was that there is something we could do about it. Now, that's like on the personal level. Does that still apply? You just touched on it when, you know, you're ready to have a child and you're looking for a partner. If we're both a carrier and, you know, whether that's both of us taking blockers, as you, as you kind of talked about in certain examples, how does that work? Like, you know, if the likelihood of cystic fibrosis, if we're both carriers and then, um, you know, there's a chance that, that, uh, our offspring will have that as well. Um, How do we go about mitigating that kind of risk? Or is it just like a, hey, now I know and now I know there's a higher likelihood?

Yeah. I mean, the entire genetic thesis so that basically you can then prevent not just disease in yourself but your future children. So, let's look at the cystic fibrosis example. So, I do Nucleus. The whole genome test is actually right above me. And basically, I find out that I'm a cystic fibrosis carrier. I have my girlfriend do it. Let's say she's a cystic fibrosis carrier. Okay. Then once, you know, this couple does it, they say, okay, well, hey, let's go to Nucleus Embryo, right? And then if you look at Nucleus Embryo, you can actually pick the embryo without the disease. So that's a way where actually Nucleus Family, which is the product that identifies if you're a match or not, if you're not a genetic match, i.e., you're both at risk of passing down a hereditary marker, what then you can use is Nucleus Embryo. If you use Nucleus Embryo, you could actually then pick the embryo without the hereditary disease. So, suddenly you can start seeing how much, literally speaking, genetics can stop your child of having that horrible debilitating disease. And, this is disease that would've been completely invisible without a genetic test. So, that's the power of a whole genome test in the family planning context. It's actually profound. It's probably the single greatest preventative measure that's ever existed. Why?

Yeah.

Because if you get a disease, it's very hard, you can't cure it basically. Through software and through a swab, you can actually prevent any disease. That's remarkable.

Yeah, I mean, that, that would change the way we think about a lot of things. And so, uh, you know, I'm sure you've been asked this many times, but do you know, is it in the thesis to believe that, uh, we start dating based on genetics? So saying like, hey, are we compatible? And I know, I'm sure we've seen some of the jokes of like, hey, uh, on Tinder, on some of these dating apps, we'll have our, our Nucleus results. But is that really kind of a— we say it as a joke, or we say it as like a reality where And that is a true question that we ask because now we have a much more view, much better view on true health and how that kind of meshes together.

Yeah, I mean, this is actually done in many communities. Look at the Ashkenazi Jewish community, for example. It's very common practice when they matchmake to make sure that people are genetically compatible.

I've done this. I've done the Sarnoff Center test for genetic compatibility.

There you go. By the way, some of those panels look at a small number of genes, so I would still recommend doing Nucleus because it actually misses a lot. That's a whole nother conversation that we can have. It's so good to do genetic testing in general. But yeah, so I mean, I think absolutely. I mean, remember, I want people to remember who are listening to this, even if you're not a genetic match with your partner and you're absolutely head over heels for your partner, I hear people sometimes say, Kian, I don't want to do it because what if we're not a match? If you're not a match, it's not a problem. You can then do something like Nucleus Embryo, which is our new product. And as mentioned, you can basically screen out the condition. So either way, every couple in the United States should do preventative preconception screening to make sure they don't pass down some sort of debilitating disease to their child. Okay. And, I would also mention—

yeah. Yeah. Could you just double-click on Nucleus Embryo just so we make sure we have our definitions right? What exactly is it?

Yeah. So, Nucleus Embryo is our newest product that we just launched. If you're on Twitter, you probably saw it. It flew. Great product. Basically, Nucleus Embryo is a way for parents undergoing IVF to genetically optimize their child. So they could basically screen for diseases like cancers all the way to something like IQ or height. Uh, it basically helps parents give their child the best start in life. And so we actually combine our Nucleus Family product with our Nucleus Embryo product to basically ensure that no hereditary markers are passed down to someone's future child, as well as to make sure that people are at— uh, people can basically pick their embryo based off what matters most to them across really any vertical.

The audience has to know. I mean, we just talked about like, yeah, it makes sense completely that we would date based on genetics. So is that something you're doing now?

Me personally?

Yeah.

Yeah, absolutely. You know, if I go on a date, I say, you know, where'd you go to school? And I say, what do you do? And I say, have you done Nucleus? And then I see if we match.

Is it an immediate red flag if they haven't?

I mean, for sure, right? If they haven't done Nucleus, I mean, whew. Yeah, I mean, can you even— can you even continue that conversation is the question. But no, but in all seriousness, I mean, I, I would though. I would. I seriously would. I would say, hey, can you do this genetic test? And then I would make sure. I mean, I think my theory with dating is like, you know, people look at people's medical records, they look at their family, they look at their Instagram, they look at, you know, the spot on their belly button when they're trying to find a partner, right? They look everything about them. Why would you not look at their DNA, right? If you're at risk of passing down a severe genetic condition to your child, Which is by far would be the single most consequential decision of your life. You should almost certainly just swab your cheeks to make sure, hey, my child's going to be healthy. And again, I want to reemphasize this. Let's say you go on a date, you fall in love with the girl or guy, right? You fall in love. You're like, this is the one. We're going to get married. Holy moly. And then Nucleus says, well, you should probably do this genetic matching thing. Or excuse me, you tell your girl or the girl tells you, hey, we should probably do this genetic matching thing. And then you get nervous because you're like, oh, but what if we're not a genetic match? Even if you're not a genetic match, then you can do nucleus embryo. You can make sure that you have healthy children. So either way, right, let's say you are a genetic match, amazing. Go, you know, have kids, have fun. Let's say you're not a genetic match, you can do IVF and then make sure you can have healthy children. But either way, whether you are a match or not and you love the girl, you love the guy, you can go and you can have healthy children. And so I think that's what's so amazing, which is You know, there's still millions of babies born with severe genetic conditions. In a single generation, we can actually eliminate all genetic disease from the population. And, I think that's pretty remarkable.

Yeah. It would eliminate a lot of the need for things that we do now. I mean, monitoring a lot of these biomarkers if we know them preventatively that we're at risk for them.

Longevity begins in DNA and DNA begins in embryos. So— No, the

logic's there. I mean, okay. So, it's obviously a controversial thing. I'm sure, again, back to the Twitter— Controversial? No, it could be. I'm just messing with you. What's it called? So, like, we talked about the health side of it, right? And I'll say, you know, you can't have a healthy kid, you go do nucleus embryo. On the opposite side of it, what if I'm trying to optimize? I want to have a son, I want to have a 6'2 son, you know, whatever else I want. Where do we toe the border of, like, we're optimizing for these things that become superficial in society and now the rich get to do all these, you know, fancy things for their kids and so forth. And that's just one Negative edge case, right? We could think a lot of other things that can happen.

Well, there's a lot of thoughts here. For starters, there's no difference. So, if I said to someone, hey, I'm going to optimize my health, nobody bats an eye, right? In the longevity movement today, we see people everywhere every day saying, hey, I want to optimize my health. I want to, whatever. I want to live as long as possible. I want to thrive. When people talk about optimizing their health, they don't mean I don't want to get Alzheimer's, right? They don't just mean that. Yeah, they don't want to get cancer, they don't want to get Alzheimer's, they also want to thrive, right? They want their brain to be as sensitive as possible. Yeah. They want their body to be as strong as possible. In other words, there's really no difference between trying to avoid disease and thriving. These are actually on the same end of the coin. In other words, let's say if you look at genetically speaking, what is longevity? And you looked at the genes that are associated with longevity. Do you know what genes are associated with longevity? They're the same genes associated with Alzheimer's. Fascinating, right? But makes perfect sense. If you don't have those markers for increasing risk for Alzheimer's, obviously then you're going to live longer. So, you can see that actually diseases and traits are quite inextricable. Another great example I always use is schizophrenia. We find that people with genetic disposition for schizophrenia tend to be more artistic in nature. They tend to be more founders, right? Obviously, that makes sense. I mean, madness and genius can converge. Of course. And so, when you start thinking about it, you start realizing there's really an arbitrary line in the sand between diseases and traits. And, you already see that today in the longevity movement. People already know that intuitively. And so, the same logic applies to embryos. When someone wants their embryo, they don't want the embryo or their future baby, they don't want the future baby not to just have disease, they want them to thrive in life. And now, genetics can be another tool in the toolkit to basically help parents give their child the best start in life. alongside a good education, alongside nurture and care and love. I think that's a beautiful thing, and that's using modern technology to really improve human welfare. On the point that you raised regarding rich people having access, I mean, let's be clear, the ethos of a Silicon Valley startup, the ethos, I mean, Nucleus, literally speaking, exists so everyone can have access to it, right? Yeah, for sure. There's a reason why a college student has this phone, And a billionaire has this phone too, right? Because the ethos of a startup is to give everyone access cheaply. That's how capitalism is. And so, Nucleus is following that same principle. IVF is going to be cheap, it's going to be ubiquitous, and genetic optimization is going to be available to everybody. And so, when you combine these 2 things together, you start realizing, of course, people everywhere, anyone anywhere is going to have the ability to genetically optimize their children. Which, as mentioned, doesn't just mean not having disease, it also means thriving.

That's fair. I mean, I think it's structured really well because, yeah, in theory, like, I work out to be healthy but also to optimize. But do we draw a line at all? Like, if I use Nucleus Embryo, I have full rein for any choices? Or at some point, if it's like, if all I'm choosing for is purely cosmetic, is there a line drawn there? Or is it like, you know, it's super hard to do that. So I'm just curious, like, how you guys think about that.

There's no such thing as Picking purely for cosmetic, right? Because let's say you go to your embryo and you don't look at any diseases. Obviously, you're never going to do that. I mean, what's the point if the baby is tall but has a debilitating disease, right? That just doesn't make sense. In other words, in picking for diseases, you're also picking for cosmetic. You're making a value judgment about the world. And so I think the thing to remember is that diseases and traits are not something that are separate from each other. Again, they are one of the same. This is really, really important. Think about height. The extreme end of height, the extreme version of any trait is a disease. Height, Marfan syndrome is one end. Dwarfism is on the other end. IQ, one end is autism. The other end, you're cognitively impaired. And so from this perspective, you start realizing again that there's been an arbitrary line in the sand about what insights people should and shouldn't have access to. And you see this all the time. Once a baby's born, people want to give their baby the best education. They want to give the baby the best healthcare. Do we say when Someone gives the baby the best education or trying to send them to the best school, do we claim the parents are pulling some sort of horrible optimization trick? Of course not. The parents just want to give their child the best start in life. And, the same thing now can begin at the genetic level.

That's super fair. I mean, I think it's useful to have these kinds of conversations because I think it sheds light to that response. Alternatively, you could look at it without that and think other things. I want to jump into genetics tying into longevity. We covered a little bit. But this is a space specifically I work in and super interested in. Obviously, genetics will play a role in healthspan longevity, but how on earth do we correlate the data? I think about this all the time, and I've heard about your company a good bit ago, and so I reference it whenever we think about full-stack health. We can go from genetics to continuous monitoring to all these at-home blood labs and so forth, and you have this full view of health. But then, let's go to the research and say, hey, can we correlate Some things we can for sure, but can we correlate some genetic disposition to some consistent biomarker being in some different way and then having some consistent trend with wearables? A lot of this stuff hasn't been correlated before. And so, we're fully entering a new era of research. And if a platform, whether that's yours or other platforms that say, hey, you are healthy, and that's based off of correlations that haven't been made before, how do we really go about that? How do we think about full-stack health when this is just so new? We've done genetic screenings in the past, but We haven't done it to this extent, this consistency, and we just have not had this much data accessible. And, just to double-click on this as well, is who's interpreting this? We're all about, in the modern day, is giving the consumer their health back. So, that assumes physicians are kind of involved, semi-involved. Even if they are, this is, from an infrastructure perspective, hasn't been done before, right? Medical students don't go learning on what is the correlation of if genetically I'm disposed to being insulin resistant and then my CGM says something completely different and everything throws out of whack. It's just not something we learned about. What does that look like? Is this entering a new era of research or how did the next 5 to 6 years play out?

Great question. One thing I would note is that I think is the single most underappreciated part about the Nucleus application is we're actually the first consumer health application to my knowledge ever that has integrated your whole genome, i.e., all your genetic analysis and genetic risk assessments with your blood. With your BMI, with your age, with your sex, right? And beyond other non-genetic information together. In other words, we actually, when we calculate someone's risk, we factor in not just your genetic contribution, but also your personal lifestyle factors as well. And so this combination allows us to get much more accurate overall risk assessments. Where do these where do these estimates come from? Well, as you can imagine, you would need a large database of people with their genetics. and also their lifestyle and blood information, then you could see depending on someone's given blood levels and given genetic information, someone's overall risk for a condition, right? You can actually start doing nice statistics here to make predictions. And so, I would say these correlations already do exist and they're actually in production in Nucleus today for all our whole genome customers. Importantly, I would say that it's only going to get better. So, for example, eventually you want the Nucleus platform to say, hey, Kian, As a 25-year-old male living in Brooklyn, wow, you had super high LDL levels in your last blood test. That's actually no surprise because you're in the 95th percentile for your genetic risk for high cholesterol. We found people with similar sex, age, and genetics as you saw a 10% reduction in their LDL levels when they did this specific workout tracked on your Apple Watch and ate this specific diet that we just ordered for you via DoorDash. In other words, you want to bring all these different pieces together into a consumer-centric, quantified, real-time application. And, the genome is the singular diagnostic test that sits at the foundation of every other possible diagnostic and lab test including notably blood tests. So, you see people all the time already kind of bringing together their Nucleus results with their different blood test results and then understanding much deeper what is driving the fundamental metabolite.

I mean, I'm excited just hearing it because this is something I'm obviously fully into, but I want to push back on it for a quick second. Sure. That would imply though that you need a bunch of data, right? For it to say like, hey, we notice other people over the course of time and the timelines obviously have to have some extent because maybe in the 6 months you have a drop in LDL-HDL and then maybe 6 months later there's a pickup again. And I don't see a scenario where that would be the case, but just like again to argue edge cases here, it requires data. So my point when I said we don't have data, So it seems like Nucleus is pioneering this, but because they're pioneering it, what is the gold standard benchmark? It's like, okay, so based off of 5 people, we now can give the 6th person a recommendation, which is, yeah, basic statistical analysis. But with health and with America being such a diverse country, especially if we're operating, talking primarily about the United States, it gets super complex and difficult because what may be the case for one person and say, okay, for you, whatever is running, has that 10% decrease for someone else that actually increases that same marker a good bit just because there's factors that's not being classified into. So, how do we go about thinking like that when, yeah, it's just like you guys are pioneering both the data collection, which means you're like the validation and the test set. How does that work?

So, there are large biobanks. So, what you're implicitly suggesting here is there needs to be large databases with as much health information that possibly exists. That's basically what you're saying, right? You need someone's genetics, you need their blood, and it needs to be longitudinal.

Yes. Over the course of time. Yeah, exactly.

Yeah. And so, these databases, they do exist. I mean, the foundations of which I should say exist. I think on the wearable front, it's coming along quite well actually. If you look into the All of Us program in the United States, for example, they're trying to get a million genomes and they also collect a series of other information including notably wearable information. And they're starting to do deep statistical analyses to do exactly that you're describing. And so, I think I agree with you that it is going to come in part from the private sector, this massive data aggregation and analysis over a period of time, and that ultimately, someone's going to start pulling these pieces together and get far greater insight. And then similarly, I think if you look at the public studies, public governments, They, you know, when you think about a biobank, a biobank is principally as quantitative perspective of someone's health as possible, right? Sure. So basically quantitative molecular measure of everything, ideally, ideally almost everything of their health, and then integrating that with wearables and actually tracking those patients in the biobank over time. That combined with the private sector's efforts is going to combine together where companies can use public and private data to build better and better models. That, to your point, not just better assess risk but also can give more targeted recommendations to the patient. And so, when I gave my example of the reduction LDL based off of some exercise and some diets, obviously you would need, to your point, some sort of validation dataset, right? You would need some testing dataset that you could actually show, hey, this is actually what happens. You also test the model in some independent cohort and make sure it's actually Correct. But the foundation of the data is there, and I think you're only going to see it accelerate. I think the meta point is that medicine today is data science. And from that perspective, you start realizing that the kind of old school qualitative and sporadic kind of white-shoed, like kind of posh medicine is getting replaced by computers, AI, and data. And this is an awesome transformation, I think.

No, super fair. This is sparking a thought. I was just at a talk with a researcher from DeepMind that was working on AlphaFold. Do you think this plays a big role in the future of any kind of drug development or drug personalization, knowing that a lot more people now have genetic sequencing and then keeping that all in a big database and seeing how things affect them over the course of time? Is that something that's actively happening? Is it something that you guys are thinking about? How do you think that changes the way we go about medication and drug development?

Yeah, absolutely. So, one thing to understand about drug development when you think about genetics is one thing that is always very important for drug development is mechanism, right? So, researchers are always trying to understand the genetic basis of things like Alzheimer's or Parkinson's, especially in neurodegenerative diseases where there's less drugs. And if you look at these conditions, what you basically do is you take a whole genome test like the one Nucleus runs and you wanna find rarer genetic markers. Generally, the intuition for genetics is that the rarer the genetic marker, the greater the effect the marker has on a given condition, right? Meanwhile, the more common the genetic marker, the lower the effect it has on average. This is kind of evolutionary reasons. And so, in other words, if you wanna understand mechanism and elucidate mechanism of common phenotypes, What you would do is you'd get a whole genome and you can start kind of mining for these rare markers. These rare markers can then give insight into some sort of mechanism which then can be used for drug discovery. Maybe that's too technical of a description. That's fine. Basically, you can use whole genome to get genetic markers that tell you something about pathways that then you can target with drugs. And so, genetics is going to play a fundamental role in drug discovery. And I think if you look at 23andMe, 23andMe is interesting because they actually use a small snapshot of DNA. So if you think of your DNA as a 1,000-page book, 23andMe looks at one page, a very small fraction. And still, you can see Regeneron went in there and tried to buy it for $250, $300 million, which of course, you could wager, I would wager that actually wasn't for the data. I think the data's actually not very valuable, but still, they went in there and tried to acquire it. I think there's notable here that with whole genome testing, which is the next generation of genetic testing, you're going to see a dramatic, dramatic, I think, boom to drug discovery efforts. And just to be clear here, Nucleus is a company. We serve consumers. By default, we don't share any genetic or protected health information with any drug companies. I want to make that very clear. We're HIPAA-compliant entity. So people who do Nucleus, The genetic information is only used to provide you with better care, just in case anyone listening is wondering as I talk about drug discovery.

Yeah, no, absolutely. Well, yeah, that's important to know. But, it might be a stupid question, but you talk about how the costs are going down. 23andMe didn't give a good look of the whole genome. Is Nucleus and the technology that's available today looking at the full and total genome, or are there things that are still being left out? In terms of genetic sequencing, we look at the whole genome. But, how much far is like what's the next evolution from a technological perspective or is it analysis on the current whole genome or is there more that you can get from different types of testing?

So, this is a whole genome test. It's something called a short-read whole genome. So, you basically get the vast, vast majority of the genome. There's specific regions like around centromeres and telomeres that the short-read genome struggles in. 'Cause it's like repeat regions, et cetera. So there's some technical limitations, but for the purposes of like a population-level screening, it is a whole genome test that is 99.9% analytically validated that you can basically flag pathogenic markers genome-wide effectively. There are long-tail cases where like there are longer genetic markers that are really rare that the technology might pick up— excuse me, the technology might not pick up. They're very rare. And usually, that's mostly relevant in a clinical genetics department if there's some baby born with some really unknown de novo condition or the like. But yeah, I mean, the technology we're using, it's sort of like going from a horse carriage to a car. A Mercedes is a really good car. Do you really need a Bugatti? Not really. You know, it's kind of like that. That's the way of thinking about this. Like, 23andMe was, you know, the horse. Nucleus is a Mercedes. And then it's like, yeah, does a Bugatti exist? Yeah, but you basically, you probably don't need a Bugatti. That's like, yeah, that's basically the analogy.

Yeah, no, super fair. I want to shift gears a little bit to a topic, and probably the most exciting topic I wanted to talk to you about is epigenetics. You know, I'm going all the ChatGPTs and looking all the things I can up, and everyone's got a different answer for me. I even talked to someone getting doing pretty deep research in epigenetics and obviously a pretty biased answer there. But, what's your take? Is epigenetics real? Give me just the breakdown on Kian and epigenetics.

What do you think about epigenetics? I'm just curious.

Oh, I don't know. I honestly, I don't. Genuinely, this is one of the few topics in genetics that I've actually tried to read as much as I can about. And, it's so blurry as to what it actually means. Like, yeah, okay, environment can change your genetics, but like, what does that mean on the sequencing level? Like, would my whole genome test change from generations from, you know, different things? But like, I think there's some belief in it that like, there's a good bit of instances in different cultural groups with like generational trauma or just like these kinds of things. I think there's definitely some correlation to epigenetics, but I'm too clueless on the subject to give a true answer, and I'm a lot more excited about what you have to say.

So, as a general rule with epigenetics, the way I kind of— a couple things. First and foremost, obviously, just so people understand, when people talk epigenetics, you're not changing your fundamental DNA sequence. So, if you do Nucleus and we read your DNA, we're getting the ATCG read of your DNA, all your whatever, 46 chromosomes. And we're reading your DNA and we're not looking at any methylation, which is commonly what people think of when they think of epigenetics. We're just looking at the germline DNA. And so, today, Nucleus does not do epigenetics. Now, to address your question more directly, I think a lot of things. One is the thing to remember is always to take a step back and remember where a scientific discipline is in the sort of broader kind of research. What do I mean by that? If you think about kind of hereditary genetic testing, which is what Nucleus does, it goes back all the way to the late 19th century to a monk named Gregor Mendel. I mean, we all learned this in school, right? Gregor Mendel was playing with peas. And then when he was playing with peas, he started discovering things about heredity. And that's awesome. If you think about epigenetics, epigenetics was, you know, really started to be established in, you know, 1970s, 1980s. And then really kind of took off more post the Human Genome Project in the 2000s. In other words, if you think about like the research effort and timeline that has gone into epigenetics, it's probably like, let's say decades, you know, like maybe 30, 40 years. Genetics, hereditary genetics has been around for probably like 150 years. And so, in other words, you have almost, let's just say a century more of research and understanding. And what I'm trying to say here is that genetic testing technology, the kind we do, is in a far more sophisticated state. I mean, looking at epigenetics without looking at your genome, you know, it would sort of be like, I don't know, I don't really, it's just like, it would be kind of crazy, honestly. It would be, I'm sorry, no analogies come into my head right now in terms of what it would be like, you know, but it's just like not, it's just not right. I mean, you need to run the germline test because don't forget you come from DNA. Like literally you come from DNA. Like that's where you come from and that shapes everything about you. So that's my first point. My first point is more broadly on this idea that epigenetics as a discipline, you should be aware that it's a new discipline. And it being a new discipline, it is dramatically behind like germline testing where the different associations that we use, the different mechanisms we have are far more elucidated impacting every single one of your disease risks, right? Sometimes people do these like biological age scores And they're like, oh my God, my biological age is like I'm 8 years old or something. And then, I'm like, have you done a whole genome test? And they're like, no. And I'm like, your biological age could be 8, whatever the hell that even means. Who knows how they even derive that model? But, you could have a genetic marker that could, God forbid, God forbid, that could kill you at 25. And, you could have— you know what I'm saying? This is serious stuff. Yeah. We have patients who are young who do Nucleus and they identify genetic markers that could literally kill them. But then, once they do nucleus, they can identify the next step and actually prevent the condition. I don't want to scare people, but I've seen it directly because of my cousin. These things are real. Yeah. And so, I think that's the thing I always found confusing about the epigenetics. Someone would do a lot of epigenetics and then they miss on the fact that, again, their biological age could be 15, they could have an E4E4 marker dramatically at high risk for Alzheimer's and they get Alzheimer's. And, they just had no idea that that was the condition and that was the mechanism. Remember that people don't die. People usually die from chronic disease, and chronic disease usually starts in some region, right? It's not like your entire body gets cancer at first, right? Cancer is usually localized somewhere and then spreads. And so, you're not really trying to say, oh, my biological age is 5. You're trying to basically, to the capacity that you can, prevent the thing that you're more likely than not to die of. And genetics is one key piece of that. And so, When you think about this logic as well, I think epigenetics kind of falls short. That said, I don't want to knock epigenetics too much, right? I'm all for frontier diagnostic testing. I'm all for different methylation testing. And I think it's interesting. I think it's interesting as a complement to germline DNA testing. And on my first point, it's only going to evolve. I mean, the research is going to get better. You're going to understand more and more kind of what the implications of different epigenetic markers are. Yeah. And yeah, I think it's going to be really interesting, not just epigenomics but proteomics and other omics coming together.

Have you seen people do anything super weird in the epigenetic field whether it's optimizing however they can optimize their own epigenetics or any crazy research that sticks out to you?

In

epigenetics? Yeah. It can be the most out there. I, I gotta, I gotta throw that one out there.

I mean, people have tried to gene edit themselves. That, that's always very notable to me. Uh, on the epigenetic front, I don't really know.

I mean, what's the, what's the, what's the form factor for, uh, like, as in CRISPR, or in what sense?

Yeah, yeah, they try to inject themselves with CRISPR, presumably. There's some, like, delivery mechanism they use, and, and then they inject themselves with it.

Okay.

And I, I, you know, the question of if that works, I mean, You might get some— Is it? I mean, I think one thing about adult editing versus germline editing is that you have to remember you have to get a lot of cells, not just like one, right? If you're an embryo, obviously you just target a couple of cells. If you're, you know, adult, it's a different story. Also, it's like you have to— like the delivery mechanism for CRISPR is just as important as CRISPR itself. Like you have to get the CRISPR in the right place, right? Like, you know, and so I think that's a good point. Also, there's still off-target effects of the device. But, it's gotten much better actually. You can give much more precise edits to the genome.

Yeah, that's super fair. What's like the— I want to wrap up here before we jump into some rapid fire. It sounds like there's a lot of exciting things happening in the shift in healthcare as we incorporate genetics. What's the grand vision? You've kind of dabbled in it a little bit, but 5 years from today, what do we do with genetics? What does Nucleus look like as a company?

I think you're going to be building this health and reproductive stack. So, I think you're going to bring together sequencing DNA, analyzing DNA, and engineering DNA. And, you're going to see that basically across the entire reproductive stack again from preconception to conception to birth. That's one.

Actually, I want to click on this. I want to add a quick caveat. And, who's the one that's in charge of it is a big question I have as well. What does it look like? Okay. So, the person themselves, not a physician or someone else looking at it for them.

Principally, everything we do at Nucleus is for the customer. We really believe in kind of what's called participatory medicine or this idea that the customer should have agency over their health and that of their children. And, I think that medicine's changing as you know. People want their doctors to not be the arbiters or the gatekeepers but instead to be facilitators for people. And, I think that's really important. On the health side, I think you're going to be building this real-time consumer-centric quantified health platform that's going to be integrating someone's blood, genetics, microbiome, wearables. It's going to be able to flag underlying molecular signals prior to any obvious phenotypic signal like a cough or something. And basically, you should be able to prevent any disease theoretically if you collect enough data. That is, I think, really, really interesting to us. So between these 2 things, and they're actually much more related too, because As you build the reproductive stack, you're going to actually get a baby. And then, once you sequence the baby's genome, guess what? I guess I said DNA is just the beginning. You want your baby to live as long as a healthy life as possible. So, there's going to be applications that exist not just to optimize your genetics like Nucleus just launched, but also to really optimize your entire baby's health as well as you do for adults. So, longevity is going to come not just for adults, I think it's going to be for children as well.

That'll be super exciting. Um, I want to jump into some rapid fire with you. I think these, some of these will be pretty fun. Um, I'll just give you a quick question. Quick question. Just give me the first thing that comes to mind. How does that sound?

Great.

What's the weirdest person you've ever met?

Weirdest?

Weirdest. In like a nice way. Or in a mean way, but nice way works too.

I know a lot of, I know a lot of weird people. I have no idea.

We're looking at weirdest. What sticks out? What sticks out to you?

The weirdest person I've ever met? I don't know, probably someone at some Founders Fund party. I've met some weird people at some Founders Fund parties.

That's

fair. That's fair. That's a sufficient answer.

I hope not the TBPN guys.

No, they're the most normal. That's why they did the podcast.

That's just why they're killing

it. They're normal. That's why they're killing it. Exactly.

I got it. What's your most contrarian belief?

Classic. I don't know. I've been asked this. I mean, I have so many here. Here's a fun way of answering this question. I think my most contrarian belief is that a better question would be, what is something that you believe to be true that everyone else also believes to be true?

Yeah. Okay. Let's run with that one.

Are you asking me?

Yeah. Oh, you want to answer the question?

You asked me a question.

Yeah. I, oh, I'm just, I'm playing goalie. I'm bouncing it back.

Uh, what is the thing I believe to be true that everyone else also believes to be true?

Yeah, I'll think while you give me an answer.

Okay, great. So I have no time to think. I'm just kidding.

I gotta make it hard for the guests.

I think it's interesting, this question, because you start thinking about what does everyone actually believe to be true? And the most obvious things that you would give, for example, the first thing that came to my mind is like, oh, that probably hard work and determination and grit is probably the singular most important thing to succeed. But I actually think that would be controversial to some audiences. And so, I actually, as I think about it, I'm like, what do I believe that everyone else also believes is true? And then, what do other people also believe is true is also maybe just as interesting of a question. If I took 100 people in a room, what can I actually get them to agree on? all agree on. Uh, and so then now I'm sort of lost. I don't know. What do you think?

I, I think we can make an argument for peace. I mean, what's the statistical chance that we bring like a warmonger into the room or someone with like a lot of hate? I feel like that might be, that might be a—

I think if you said 100 people, at least, at least one would probably be like, at least one, I don't want peace.

Yeah. Maybe like peace and no war.

Maybe like food. Food would be good to be like, okay, we like food. But then someone's gonna say no, they don't like it. No, someone's gonna say no. Someone's gonna say I don't really like food.

I don't know. I think 100 people, we got a good chance. 1,000, we might lose this. Um, well, we'll jump to the next. What, what, uh, industry or breakthrough you're most excited about outside of health and wellness genetics?

Probably the artificial womb.

As in virtual reality?

No, no, like, uh, like, like, uh, being able to Basically grow a baby outside a human womb. That's why it's, you know—

Is it gonna happen in a humanoid?

No, I don't think you need a humanoid. Well,

no, but just to make the experience feel more real, more human-like.

I think if you want to make it more human-like, you should just do it in a human.

That's fair. That's fair. What's the best thing your parents taught you?

I think my parents taught me many things. I think the most important thing is just to be like, kind of like a— I think my mom did a really good job of like, you know, there's a way that people show up to the world, right? There's a way you talk to people. There's a little respect you give anyone, no matter their background, no matter where they're from. It has nothing to do with smarts, has nothing to do with even determination or anything. Just has to do with respect and kind of— there's a Farsi word for it. It just means kind of like manners, really good manners. What's that? Being respectful, being kind, being good to people, showing up, lifting up a room. I think that's the most important, one of the most important things my mom really instilled in me.

Would you say she did that verbally or by example?

I think both. And, you know, by ex— you know, I think if I didn't, you know, say hi to someone when I entered a store or something, my mom would like, you know, yell at me. And so I think I became very good at being like, okay, like just like welcoming, you know, nice, just like being a nice person.

Yeah, that's amazing. It's not too many of those out there in the world. Last one for you. I always like to play this game with the guests. Teach me something interesting, something that we haven't talked about. I mean, you've taught me a lot so far, but something we haven't talked about, something that's out there that most likely most people listening to this have never heard.

Hmm, on any topic?

Any topic, free game. Prefer— I mean, I'm sure you could teach us a lot on genetics, but let's, let's, let's make it harder for you. Something outside of, outside of Nucleus.

Do you want to give me like a guiding topic? I mean, ah, there's so many things. I mean, uh, I don't know. I mean, startups more generally, I could give a lot of advice.

Startups, like, yeah, what's some like super unconventional startups?

Here's a random piece of startup advice. When you're fundraising, who introduces you to investors is just as important as the pitch. A lot of people don't realize that.

Like an exited founder or like an exited founder of the portfolio?

Maybe they're in the portfolio. Yeah, maybe they have a strong relationship with the GP because the first thing the GP is going to do after they— if you talk to them, is they're going to call their friend. And so remember that. So you always want a quarterback in your round, basically, who can help you pull your financing round together.

If I have like a founder of an okay portfolio company that's not doing too hot, make an intro, is it better at that rate just to go cold or do I still make the warm intro?

I think it depends on the relationship that they have with the GP. Like if it's some like really random person in the portfolio, I would say no. But if they're like kind of homeboys with the GP, then I would say yes.

Is this the strategy you took? What you guys raised? You guys just raised a Series A?

I learned from experience, so I didn't know anything going to pitch the seed round. I'm thinking about the seed round, man. You don't know anybody. You gotta figure this stuff out, man. So

that's the fun part. Well, Kian, thank you so much for hopping on the Silicon Fox Podcast. It was a pleasure and love to see you here again.

Thank you so much. Thanks for having me.

Absolutely.