The Quiet Revolution in DNA Sequencing | Nucleus Genomics

0:00I think we're in the age where there will be a trillion dollar consumer healthcare business. and that business is going to be integrating in the entirety of someone's health data on the platform. I'm not just talking about your Apple Watch, your Whoop, your Eight Sleep, your levels. I'm also talking about diagnostics, lab tests, like sequencing, epigenetics, blood tests, urea analyses, et cetera. There will be that platform. And genetics is a huge part of that. If you were going to collect the single most consequential piece of health data about someone, you'd collect their whole genome data. DNA is the foundation of your health.

0:39And I think that's something that actually gets often missed.

0:53Welcome to Sorcery. I'm your host, Molly O'Shea. Today, we have Kian Sadegi, founder and CEO of Nucleus Genomics. Nucleus is a health platform designed to integrate your DNA into your daily life. Nucleus uses whole genome sequencing, which reads a thousand times more DNA than other tests, helping you uncover how your DNA influences many things about you, from your risk for heart disease to your IQ and more. They've raised more than$18 million in venture funding to date with the last round led by Alexis Ohanian of 776 with additional investors such as Peter Thiel's Founders Fund. A special thank you to Corey Levy, founder of Z Fellows and investor in Nucleus for the introduction.

1:36This is a really fun conversation and we uncover all things genomics, health, and their recent product launch, Nucleus IQ. I hope you enjoy. Hi, Kian. Thanks for joining us. Hey, Molly. Thanks for having me. Well, I know you just got off of a very popular X Live with Alexis Ohanian, Delian, a couple of renowned scientists. And this was all to discuss the launch of Nucleus IQ. Yes. Could you share more about this? What was the live about? Yeah, absolutely. The live was an amazing space for our lead investors, our scientific advisory board, and kind of customers, et cetera, to all come together and talk about the public launch of Nucleus IQ.

2:24I think we heard some amazing anecdotes, not only from sort of the Silicon Valley tech investors, but also from more classical scientists, traditional geneticists, both super excited about the release of Nucleus IQ. And I think the reason for this, why across expertise, there's such kind of unanimous excitement is because everyone is excited about Nucleus' mission, which is integrating in genetic insights into everyday life. We mean that from the individual health perspective, which is about looking at your DNA and predicting your future health. We mean that from the generational health perspective, making sure you can use your DNA to have healthy children.

3:05And then, of course, the one – the only thing that we're talking about today, which was personal discovery, using your DNA to learn amazing new things about yourself that you didn't know, such as your IQ or longevity. And so I was doing a demo of the Nucleus IQ report. It was a little buggy though. So maybe I'll do it again now, Molly. What do you think? I think you should do it. Do a demo. Oh, yeah? Okay. Yeah, so what I was saying in the live stream was that, you know, nucleus IQ, the function of it is not to predict your IQ score. The way it works is it basically tells you people with similar genetics to you how they tend to score on an IQ test.

3:50If you want to get your IQ score, you should take an IQ test. If you want to understand the genetic contribution to your IQ that we can measure today, I would then recommend doing nucleus IQ. So I'll share my screen here to my kind of nucleus portal. I think this is super cool. Here we go. Screen. I'm going to share this. So this, you can see my screen, right, Molly? It's, yeah, we can see it. Okay, amazing. So here, first off, yeah, I'm higher genetic risk for schizophrenia and a couple other things, which is pretty interesting. I think I've released some videos on that publicly about kind of going through those results.

4:28But you can see here IQ, it's, you know, brand new report. So if you're a Nucleus Premium member, which is if you bought our DNA kit, you actually get access to this. I'm going to click on this. The first thing I want to highlight is actually this disclaimer here. I'm not going to go through each of these points, but I just want to reiterate that the goal of Nucleus IQ is not to predict your IQ. It's to tell you your genetic contribution to your intelligence. So I'm going to continue the report. Beautiful graphics here. As you can see, people with my genetics tend to score higher on an IQ test by around six points.

5:01I think this is super fascinating because a lot of people don't even fully recognize that at the frontier of science, we do already have associations with genetics and intelligence. And we really believe in giving these insights to customers. If you click down here, you can see a genetic score. So what this does is this is taking over 550 ,000 DNA differences and combine it together into a score. The higher the score, the higher people with similar genetics to you tend to score on an IQ test. And the lower the common genetic score, polygenic score, Z score, all those terms work, the lower this number, then the lower score someone tends to get on an IQ test.

5:44So I'm above average. I'm very curious to see. I think my sister just sent me a text saying that she was actually higher than me. And she was completely bantering with me in my DMs. I think she was 99.1 percentile. I think mine was 97 percentile or something. So I guess she wins this one, Molly. Well, there you go. the sister usually wins. Yeah, that's true. Okay. So within the nucleus IQ analysis itself, could you just break down all those elements again? So what is the consumer getting out of it? Yeah, that's a good question. So what someone's really going to see is the genetic contribution to their intelligence.

6:26So basically the higher the score that you have, the higher the genetic score, the more likely, the higher you perform basically on average on an IQ test. This is super interesting because we received a lot of blowback. There's a lot of controversy on that. These sort of insights shouldn't be in the hands of consumers, shouldn't be in the hands of people. There tends to be an opinion of certain scientists, ethicists, as well as sort of the public policy bureaucrats that people shouldn't have access to frontier genetic insights. They are sort of, they deem themselves as the brokers of genetic insights.

7:04And from our perspective, we believe anyone anywhere should have access to your own data, your own insights, and so much for to learn everything about that the DNA has to say about them. So why is that controversial? I know that Nucleus itself was kind of the crosshairs of a couple of different articles that were put out on the web from researchers from MIT and from Harvard. But could you just break down, like, why is that controversial at all? That's a good question. I think there's a lot of historical baggage, first and foremost. and then moreover I think that in medicine today people tend to think that information without any very clear clinical guidelines should not be given to a patient and with that perspective is it's a very paternalistic perspective and then kind of paternalism can kind of become gatekeeping so I think they view it as dangerous as something that given to someone could really dramatically affect them negatively, not positively.

8:09So for example, if you give someone a schizophrenia, genetic risk, they won't understand it. It's something that will kind of mess with the psychology, et cetera. We, I think, believe that one is there should be no broker of genetic insights. No one should decide for you except for you what information access you get. Moreover, we think that we can build better and better communications to explain people the kind of nuances of these scores. If you look at our reports, for example, I'm sure they don't look like any other genetic reports you've seen, right? I think they're quite tasteful. They're extremely thoughtful.

8:44They explain everything to the customer. You can get as deep as you want in the results. And we also employ, I think, scientifically sound different kind of methodologies to make sure that some of the criticisms that have usually been thrown on some of these scores don't actually apply because nucleus has such a kind of comprehensive and accurate whole genome assessment of someone's disease risk as well as their traits. Within your score in particular, and I know you posted this on Twitter, but you ranked pretty high in schizophrenia and I'm sure that was kind of shocking at first. I think the nuance is really important even when you're receiving these scores as you've mentioned.

9:29Could you just break down, even though you scored high on that, why you're not very concerned? Yeah. So someone can be very high genetic risk, but still be very low overall risk. Let me actually share my screen again and show this, because I think this is an important point. So if I come here, I'm going to go back to the summary section, right? Go to my higher genetic risk. You see it's sorted by genetic risk. I click view full report. The first result that a customer sees is that one, they don't have any really bad DNA differences, variants that dramatically increase your risk, which is good.

10:07Then we analyze these other kinds of DNA variants to determine someone's risk for schizophrenia. And you can see here how even though I'm dramatically higher genetic risk, 2.48, I think is in the 99.3 percentile, my overall risk is 1.43%. And this is actually very much by design. There's a reason why we show the overall risk first and then the genetic risk after. And that's because this is the result. And as you can imagine, a 1.43 % is a very low overall chance. So you can have a very high genetic risk, but still a very low overall risk. And this is, I think, one of the care, this is some of the care that we've built into the platform where instead of just giving out these raw scores, which can cause a lot of potential stress to a customer, by integrating it in with other non-genetic information, we're able to provide people much more holistic and complete assessments of their risk for different diseases.

11:09by giving someone overall risk, it helps, I think, ground the genetic scores. And I think that's a key feature of Nucleus. And we all like to freak out, so that'll help us freak out less. Exactly. So within that, though, you were talking about IQ and IQ tests. I think it's important to understand the differentiation between intelligence and IQ and IQ tests. um silicon valley is just so obsessed with iq i'd be really curious to break that down and understand how you're measuring iq with nucleus and then how you know you can take any sort of consumer iq test online like i'm not gonna lie like i'm kind of obsessed with that too i think it's really interesting i have this like brain training app and i track that and i think it's cool.

12:02But what is the difference between that and then also intelligence? Yeah. So at a genetics company, what we do is we show people their genetic contribution to intelligence. And you're right. We do use the word intelligence and IQ a little bit interchangeably. It's actually a thing in the literature. People tend to swap these things. Technically, the definition of IQ that we use is a lowercase g or general intelligence. That's what the researchers as we're trying to gauge in the paper that we use to build the models. The thing is, though, all the different kind of measurements of intelligence, they tend to correlate, right?

12:43So you can kind of somewhat interchangeably use these terms, even though they're not exactly the same thing. Regarding Nucleus specifically, we want to show people how their genetics contributes to their intelligence. We are not necessarily at this point, you can't from genetics predict someone's IQ. And actually what a lot of people don't realize is you will never be able to. And the reason for that is because 50 % of intelligence is environmental. The other 50 % is genetic. So even if you built a perfect genetic model, I'm gonna actually show this in the reports, even if you built a perfect genetic model, you would still have error bars in the prediction of someone's actual IQ.

13:26which I think is pretty fascinating. So that's kind of how the Nucleus IQ works from our perspective. Is there anything surprising that you noticed within the test so far that you've collected from the small cohort that's been using it? I think it's funny how people kind of interact with each other on this course. I definitely think there's a lot of kind of friendly banter. I mean, I actually just checked my phone after the live chat and every single person basically was texting me, what was your score? What was your score, what's the score, right? It's almost like, I don't know, like if we do, you know, take a test in high school.

13:59So everyone's like, oh, what's the score, what's the score, what's the score? I thought that was pretty funny. As mentioned to my sister actually had a higher score than me and she was absolutely dominating me in the, in the group chats, the family group chats, both my dad and my sister, um, had higher scores than me. Um, so now that they're like, oh, you know, these models really work so well. I'm like, oh, I'm sure they do. I am sure they do. All you have to do is tell someone they're intelligent. They're like, oh, this is legit. This is 100 % legit, which I thought was pretty funny. Hey, we'll get right back to the conversation after a word from our sponsor.

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15:08Visit Archer.com. The thing that I think is also interesting is that people are kind of getting more familiar with the idea that there can be a genetic contribution, because I think a lot of people understand that this research exists at the frontier, and a company like Nucleus is removing the access to the gatekeeper so that everyone can get their genetic intelligence score. So I'd love to actually draw that out a bit further and get into the overall history of genomics, consumer genomics, and why there is such a gap and a large opportunity now. I think you said before that Silicon Valley, the Silicon Valley model of genomics is from 20 years ago.

15:54Yeah. So 23andMe, when they got started in 2006, right? 23andMe is the company everyone always heard of. 23andMe, the cost of actually sequencing all of someone's DNA, you know, getting the entire read of it, not a small fraction, all of it, was around$10 million per sample. Obviously, way too expensive for any company to actually leverage that technology. So instead, they opted for a much more naive technology that looks at a small snippet of someone's DNA. And that technology has not changed in 20 years, which is crazy. It's basically stagnant. The genetics industry is basically stagnant for 20 years.

16:30And so people's understanding of genetics is, oh, does my pee smell like asparagus? Oh, where am I from? which I think it's time that we employ far more sophisticated technology, which is what we do. That cost of$10 million has now come down to$399. So instead of$10 million per sample, it's now$399 per sample on Nucleus' website. And using this powerful new technology, we can get the entire read of someone's DNA, which means we can provide much more accurate assessment of someone's genetic risk for diseases and their traits. And then this gets to our meta point, which is we believe in integrating DNA into everyday life, right?

17:09We believe in using not only predict your future health, not only to make sure that you have healthy children, but also for personal discovery and even how your DNA affects your metabolism and drugs. Those different buckets I've described historically were tens of thousands of different genetic tests. Today, they're just one. I think that's such an amazing opportunity now for us to seize, to scale up whole genome sequencing and give everyone access to technology that used to only be in the hands of the very, very, very few or no one. So I definitely think there's a paradigm shift in genetics. And at some point, I think it's going to combine with AI to build even more sophisticated models.

17:49I'm very excited. Do you have any sort of sense how many tests have been sold globally over the last couple of years? Do you have any sort of idea how many people are buying them? So 20th of me has a database of around 15 million people. Ancestry, I think it's around 30 million. So let's just say 45 million. Let's just say one in six people, I think, in the United States approximately have probably done consumer genetic tests. Of course, that doesn't include clinical genetic tests, right? So I would think that's a good ballpark number. But of course, the United States has 300 million people. And the other kind of side of that is, sure, that's a lot of people.

18:26why did hundreds of millions of people not get their genetic testing done, right? This is information that could save your life. There was a great study that showed millions, millions of people have a DNA difference right now that dramatically increases the risk for breast cancer, colorectal cancer, two diseases that are preventable, that there's very clear evidence-based recommendations that could prevent these conditions, and greater than 90 % don't know it. That's the problem when genetics isn't integrated in clinical practice. Life-saving insights that Nucleus can give you. Insights that you can get from a swab.

19:01It's not even like there's a blood test that doesn't need anything. It's a swab. You can swab your cheek and get a result that could save your life. Yet millions of people don't know. I mean, that's, I think, pretty crazy. And that's not anything Nucleus is going to tackle head on. And why is that? Why don't doctors start to implement that within their practices? Yeah. You know, doctors are actually not trained in genetics. A lot of genetics is not yet integrated into standards of care, and a lot of medical schools are still catching up on thinking how to integrate genetics into patient care. So it's a big problem.

19:39I think part of that is a job for Nucleus to not just educate consumers but also physicians. It's a two-pronged need that we can offer society. Do you have any sort of sense if that 90 % will trend down? Where do you think that trend will go? I mean, I think given COVID, everyone became super, super conscious of their health and their family's health because of one pandemic and you didn't know how it was going to affect you. So I'm just really curious if you've seen at all, at least since like 2020, if there's been like a shift in sort of the mentality to do more understanding of underlying predictive and preventative health.

20:25Absolutely. I think we're in the age where there will be a trillion dollar consumer health care business. And that business is going to be integrating in the entirety of someone's health data on the platform. I'm not just talking about your Apple Watch, your Whoop, your 8 Sleep, your levels. I'm also talking about diagnostics, lab tests, like sequencing, epigenetics, blood tests, urea analyses, et cetera. There will be that platform. And genetics is a huge part of that. If you were going to collect the single most consequential piece of health data about someone, you'd collect their whole genome data.

21:05DNA is the foundation of your health. and I think that's something that actually gets often missed where someone might take a lot of supplements or maybe they take a blood test or they're doing some sort of other optimization right it was funny I saw this tweet that said something like you know you can follow brian johnson but then you know you'll still die of cancer from your genes and you know on the one hand it's it's pretty funny because it's like if you think about any disease just like with intelligence actually too there's a genetic component and then there's an environmental component.

21:37And any disease you can think of, everything from breast cancer to schizophrenia to coronary artery disease to HIV and back degeneration to hypertension, there's a large genetic component. So what that basically means is that regardless of your environmental decisions, you still have to understand the initial baseline risk assessment. For some of these DNA differences that really increase your risk, like a BRCA1, BRCA2, you really, you know, your diet won't get yourself out of necessarily getting the condition. You need to take other sort of clinical evidence-based recommendations. So this is something that we think a lot about in Nucleus, and we're excited to kind of integrate in DNA into people's lives.

22:22Again, that's the mission. I guess to push on that, though, like, are you seeing more adoption within consumers, or has the COVID kind of awareness started to wane off? Yeah, I think so. I mean, I think if you look around, you know, Huberman, Brian Johnson, Peter Atiyah, I think almost a good kind of heuristic for culture is like, who are its influencers? And there are health influencers. There are people whose job it is to basically say, here's what you can do to prevent disease. Here's what you can do to live forever. We're happy to be a sponsor of Brian Johnson's Don't Die conference in September.

23:02And that conference is an amazing opportunity for all the people who kind of follow Blueprint Diet to, you know, we're the official genetic testing partner to actually get their DNA sequenced. and so I think there's definitely momentum across I think the entire country. I also think to some extent it probably skews a little bit younger but I think it kind of transcends generations too to some extent. People are more curious about their health. People want to live longer. People want to prevent disease. People want to measure what was previously unmeasurable and Nucleus lets you do that. That's awesome.

23:38That's really cool that you're sponsoring that event. Yeah, we can't wait. well i i know uh we're getting a little deep but i would love to you know just go back to the beginning and talk about you kian um so in terms of the founding of the company you started the company at 20 in your bedroom yeah you're now a z fellow and a teal fellow and it's been a couple of years um so could you just explain and share how it all began what was the founding story yeah so you know the story of nucleus actually begins unfortunately with a personal tragedy um my cousin went to bed one night and she didn't wake up the next day she died in her sleep um at the time i asked my parents you know how does this happen how does this happen they kept saying oh bad genetics bad genetics didn't understand what that meant eventually though i studied studying genetics and what i realized is that you know disease can be viewed more as a problem to be solved versus like an inherent property of human beings so i joined one of the first time do yourself gene laboratories in the country where we engineered yeast to make them eliminate.

24:41We added bacteria to make them resistant antibiotics. And I started thinking about how do you combine this kind of depth and beauty of biology with the irritability of programming because the life cycle is so long in the lab. So with that in mind, I went to Penn where I studied computational biology. And there was a distinctive moment in, I think, Bio 221, which is a genetics class at Penn. This is before I dropped out. I was there for around a year and a half before leaving. and the chairman of the biology department who was our professor he pulled up the charge of the decreasing cost of sequencing and you can see from this charge it used to cost you know a billion dollars to sequence the genome and then at that time a couple years ago it cost you know a couple thousand bucks and i thought to myself what is the world going to look like when that cost goes to zero i thought to myself you know there's a delta between what what what is and what's going to be possible.

25:33And that was the inception of Nucleus. So I dropped out of school. I moved back into my bedroom in Brooklyn and I got to work. And oh God, boy, did I work. So what did that entail? What was the early innings? What were you working on? It was a lot of very deep work in kind of statistical genetics and computational genomics to figure out how do you actually build such a piece of software? What are the actual underlying algorithms that you can use to analyze DNA? I think there's kind of different ways of thinking about this. Like there's a concept in CS about like breadth-first search versus depth-first search.

26:09And I feel like you have to go kind of very, very deep and then kind of build yourself all the way back up. So like you can read a newspaper and then pretend like, oh, I understand this space. I read this newspaper. Maybe you get a little bit more technical, a little bit more technical. Maybe you can glance through a research paper, right? But you don't really get it. I think what you have to do instead is you have to go extremely deep, so deep that you have almost what I think is this intellectual foundation. You end up at an intellectual frontier. Then once you're at the intellectual frontier, you realize how much space there is to build and that you can actually productize what you know and execute on what I described, which is building the gap between what exists and what could exist.

26:51So there was a lot of independent research. I think I filled in like 18 different subject notebooks of material. I still have those notebooks. It's actually in a safe. As I put this on Twitter, it's actually – it's one of those kind of my most prized possessions. And then eventually, thankfully, I need to raise money. And there was a lot of stress, whatever, whatever. I need to raise money. My parents were not happy, let's just say, that what I was doing. and then thankfully Corey from ZFellows wrote the first check. That's amazing. And I know that they're all sequenced in the U.S. You use U.S.