Extended interview: Nucleus Genomics CEO Kian Sadeghi

It feels like we are on the brink of some marvelous new era in genetic— what? I don't even know. Where are we? What's happening?

Well, I think you're going to see a new future of health and reproduction. And so one place to start in understanding where genetics is, is that your DNA, think of it as like a 1,000-page book. Okay, so this DNA has different chapters in it, right? It used to be really, really expensive to read every page in this book, like a billion dollars expensive. In 2000, there was the Human Genome Project. The Human Genome Project was really focused on basically mapping or reading all the pages in life, in human DNA. And so that project was about a billion dollars. Now that cost has come down to a couple hundred dollars. So you can read life's source code. You can read the origin of life, if you will, for just a couple hundred dollars. What does that mean? So what? It means we can much better predict, and then also in predicting, prevent disease, like cancers, like heart disease, like schizophrenia, like Alzheimer's, like rare genetic conditions. So in understanding where we are in genetics, it's really a story about Human health and the future of reproduction.

What we're talking about is sequencing not a full-grown adult, but an embryo.

Yeah.

But doing so with the same concept in mind. You're getting the pages of the book before the book is published.

Yeah, kind of. Yeah, that's one way of thinking about it. So you get about 50% of your DNA from mom, 50% of your DNA from dad, right? That DNA is in an embryo, which makes up of these 2 parts. And that embryo then divides and forms you, the person. So actually, if you can basically go back to the very, very beginning of life, you know, an embryo, and you can actually get a— take one of those cells, you can actually read at the beginning your story, your DNA story. So that's kind of what Nucleus does.

So the technological marvel here, the thing that's new, is not the whole sequencing of the body, it's the ability to sequence the embryo and to do it in greater detail than we could just a few years ago?

Yeah, the thing that's new is that we can now at scale and cheaply read the entire book that is life. And we can do that, to your point, in an embryo, right? We can do that in an embryo. But really, the thing I want people to understand is that if you read an embryo's DNA, that DNA file that comes out of it is the same as an adult's DNA file, right? Because ultimately, that embryo will form life. And so that embryo, when you take a cheek swab and swab your cheeks, that's the same DNA that's in an embryo's DNA as well. So that's what's new. What's new is the fact that at scale and cheaply, we can read the entire book of life, and we can apply that to adults and, well, an embryo.

What excites you about this?

Well, a lot of things. I mean, for me, obviously, Nucleus, you know, began in my bedroom. It was a dream. It was a vision. I became really inspired by actually a personal tragedy. My cousin, she very sadly, she went to sleep one day and she actually didn't wake up. Because? She had a rare condition that can cause irregular heartbeat, can cause sudden death. And so at the time, I, you know, asked my dad, who's a physician, he's an ophthalmologist. I went to him and I said, you know, how does that happen? And he said, oh, you know, bad genetics. I said, bad genetics? What does that even mean? Right? How is it possible that you could have another 15-year-old survive, live well, and another 15-year-old die? I mean, that didn't make sense to me. I was almost 7 at the time. I just couldn't reconcile that. And so with that in mind, I was always thinking during my life, like, could you build technology that stopped what happened to my cousin from really happening to anyone in the world, and that eventually led to Nucleus.

And you're doing this in lieu of going to college. I mean, is that what I have— I mean, do I have that right? You're 25.

I'm 25, yeah.

You had a fellowship.

Yeah, that came even later. Actually, even before the fellowship, I actually left school. And there's actually a story here, and I'm gonna apologize to my mom and dad for telling this story. I actually left college, and I knew because my parents are Persian immigrants, they were going to kill me.

Yes.

So I, um, actually created a fake email from a professor at Penn that said, hey, Kian, you know, you're going to work in my lab for the next year. It was during COVID And I showed it to my dad, and I was like, look, I'm going to work in this lab. And he said, okay, that's fine. And I spent every single day, 12 hours a day, for about a year building the kind of intellectual foundation of the company. I think my dad's finally forgiven me, but that's how Nucleus got started.

Okay, so you mentioned bad genetics.

Yes.

What are good genetics?

Well, I think something to remember is that if you're a parent, right, and you're a parent and you're thinking about your future child, right, if you go and think about IVF today, you should look at what people are already screening for. So just to give kind of the audience more broader context here, right? So there's different ways of conceiving. Everyone knows the typical or the quote unquote normal way of conceiving, right? You're

talking about sex.

Talking about sex, yeah.

Natural insemination.

Natural, yeah, naturally. In the 1980s, there was something called IVF, in vitro fertilization, this idea that actually you can basically make an embryo, you can fertilize an egg with a sperm in a test tube. And so the context I'm thinking about, kind of embryo testing, is very much in the context of the second bucket. DNA can still be very useful for old couples everywhere when they have a child, even if you're having sex. Why? Because ultimately, your future child's DNA is from mom and dad. So if you swab your cheeks, you can identify thousands of different hereditary conditions that you could pass down to your future child. So that's kind of the typical way. In IVF, you get an actual embryo, and you can actually do further testing in the embryo. So that's the 2 ways that genetic technology can help.

Okay, so for all of human history, you had genetic pairings based on either love, or more likely convenience, or even more likely—

Mix of all 3.

Yeah, your own mom and dad being like, no, you and you. Together, right? Exactly. Pairings for political reasons, for tribal reasons, who knows? That's all of human history. Yeah. Now parents, through genetic testing, can do something similar, except instead of their parents matching them, it's them picking the embryos that they prefer?

One way to think about this is you're a couple, you want to conceive, you choose to do IVF. Maybe you choose to do IVF because you're infertile, you have a history of a disease, and you need to do IVF. Maybe you choose to do IVF electively, which is happening more and more. We're seeing parents saying, hey, I actually could conceive by having sex, but I don't want to have sex. I actually want to do IVF. Okay. We can talk more about that. People do that. It's a new thing. It's more of an emergent thing, but it's happening more and more. People want to have more control when they have their child, for example, or they even want to do IVF because they They want to do genetic optimization, which is what we're talking about.

Yeah, tell me more.

And so let's say you're a couple, you go to the clinic. The purpose of basically IVF is to generate embryos. So again, an embryo is the beginning of life, right? It's mom's DNA and dad's DNA. Okay, usually when you're in one of these clinics, they do testing, genetic testing already. So if you go to any clinic in the country and around the world, any IVF clinic, you will see basically them doing a cursory test on the embryos. Let me explain more what I mean. Going back to the book analogy, the genetic testing run on embryos today is as if you took basically a read of the spine of the book, the front cover of the book, the back cover of the book, but you don't actually look at any of the pages of the book. Okay? Mm-hmm. So you get a sense of things like chromosomal abnormalities, like Down syndrome, for example. And then the physician and the patient will basically rank embryos based off of how, kind of morphology speaking, like how structurally the embryo looks, and also evaluating if it has the right number of chromosomes, right? Those 2 things. Then they'll rank the embryos,

right? So this is already happening on some level.

This is happening already today in every IVF clinic in the country.

They're ranking embryos.

They're ranking embryos. Every IVF clinic. It's because obviously, what does any parent want? They want to have, you know, a healthy child. They want to give their child the best start in life. Okay? What Nucleus is doing, and what's new here, is we are actually starting to look at the pages of that book, right? Because we all know DNA impacts everything from height, all the way to breast cancer risk, all the way to something like cystic fibrosis. So the old way of thinking about diseases was this idea that a really bad genetic marker causes a disease, right? Maybe someone's seen like The Simpsons before, where someone falls into some sort of radioactive material, then they come out, like, you know, with a tail or something, right? That's like, there's like a mutation. There's this idea that people have of genetics that a really bad genetic marker basically causes a bad phenotype, which often is what happens, like cystic fibrosis, for example, PKU, Huntington's.

Single gene mutations.

Single, yeah, single gene causes a bad condition, basically. Okay? That's one class of diseases. Then there's more chronic and common diseases, like breast cancer, for example. So one example I always like to give here is like Angelina Jolie.

She was very at risk of breast cancer. She learned this through a genetic test. Exactly. And she opted for, I think, a double mastectomy.

Exactly. So she had a genetic marker that substantially increased her risk of breast cancer. Now let me go back to IVF. So let's say that you were like Angelina Jolie. If you went to an IVF clinic, Today, the genetic testing that they do in the clinic would not screen for that genetic marker. Think about how crazy that is. So you're talking about every woman undergoing IVF today, if they did have a hereditary marker for breast cancer, they would unknowingly and inadvertently pass down breast cancer from mother to daughter. I find that crazy.

So in other words, they would leave it to the daughter to deal with as an adult, potentially getting another double mismatch.

They would leave it to complete chance. Instead of just doing, instead of doing further testing, instead of actually reading the pages of the book, remember, because I said the current testing they do looks at the spine, the front cover, the back cover, but doesn't look at any of the pages. And those pages can really determine the health and well-being of your future child.

Okay, so Nucleus is the new alternative. Tell me everything Nucleus can find out or predict about an embryo's future health. and makeup before it's even implanted.

Yeah. So we look at over 2,000 different diseases, conditions, and traits. We look at everything from hereditary breast and ovarian cancer, all the way to cystic fibrosis, all the way to something like PKU, which is like a rare hereditary disease. We look at something like height, even eye color, hair color.

Intelligence.

Intelligence. We give you— Acne. Acne, yeah. We give you the full range of insights there is to know about your future child. We really think it's the parent's right to know, right? If a parent's undergoing IVF, it's a long process. It's an emotional process. It's an expensive process. Why would you not do further testing? Why would you not get further information about your future child? I mean, that's something that we really believe it's the parent's right to have.

Where did this idea of a parent's right to decide come from? You mentioned the story of Nucleus, your cousin who you lost because of a genetic mutation. I understand the desire to want to optimize, to use your word, to cure disease.

Yeah.

Why not stop there? Why continue on to all these other things like height, obesity, certain mental potential disorders, anxiety, you name it, acne, etc., etc., onto and including intelligence or other performance

Yeah.

Parts of life.

Well, I think when you talk to parents, any parent will tell you, you know, life is much more than just not having diseases, right? For example, when you have a child, you want your child to be healthy, of course, first and foremost, right? If I ask my mom, like, Mom, what do you want in your children? The first thing she'd say, healthy. What does she also want, right? They're immigrants from Iran. They want us to, you know, play sports, and they want us to go to the best school. They want us to be well-educated. They want us to thrive. Life, I think, as a parent doesn't just stop at, I want my child to be healthy. Of course, God willing, your child's healthy. But it goes well beyond that. Life goes well beyond that. And so our job as a company is to thoughtfully, carefully, deliberately give the full range of insights there is to know about your future child, and then ultimately let the parent and the physician decide what and how they want to implant. When we talk about height, for example, we're not saying that you're taking an embryo and then you're changing anything in the embryo. These are embryos that already exist. These are embryos that are already being ranked today in the IVF clinic. So you're just getting more information on each embryo. What's the alternative? The alternative is randomly implanting an embryo, which, I mean, when it comes to your kids, there's probably, of all the things, you don't want to do that randomly. You wanna be very deliberate and thoughtful in your choice.

But that is all of life up until this moment.

Random?

Yeah.

Well, unfortunately, sometimes that randomness can cause personal tragedy. So it is all of life up until this moment, but when I think, and I'm sure you've had someone in your family that's had a disease, I'm sure, Kian, there's cardiac disease in your family.

Every family has something.

Every family, right? And I think when you see somebody that you love suffer, and then you think genetics is sort of a tool that at the very beginning of life, without any needles, without any surgeries, without any invasiveness, just at the beginning of life on a software platform, you can pick an embryo that is going to have greater longevity. I think that is beautiful. I mean, that is the realization of Preventative medicine, I think.

I think most people agree with you. There's been some surveys on this. A majority of Americans fully support screening for diseases, preventing suffering.

And some communities, like the Ashkenazi Jewish community, for example, they actually will pair people based off of if they're a genetic match or not, right? So you can actually take mom's DNA, dad's DNA, make sure that they're not at risk of passing down a hereditary disease. And then you could accordingly say, actually, you guys are at risk. Either you could do something like IVF, or you can basically, in that community for example, actually get them a different partner. So genetics is a realization of the ultimate preventive tool that we have today.

Most people are fully with you when it comes to preventing disease.

Yeah.

Most people are not fully with you when it comes to all these other things like eye color, hair color, intelligence. What do you say to those people?

I say, I think, a lot of things. One is that I think at first it can sound like it's scary, right? Like, you can predict intelligence from DNA? You can predict, you know, height from DNA? Height is maybe more obvious. I mean, people can look at their siblings and be like, well, my, you know, my brother is like 4 inches taller than me, right? That's not because my mom fed him and didn't feed me, right? It's because of our DNA. Yeah. Right? So that's just how it is.

But just if you think about that for a second, potentially, if your parents had been using Nucleus, They would have not selected your embryo.

My mom said she wanted a taller boy.

But does that not give you pause as you think about the lives that will not exist as people optimize for things, not realizing they're losing a Kian in the process?

No, I— first off, Kian would have still been made, because remember that even if you optimize by an inch or 2 inches, you're not actually changing most of my DNA.

You said 4 inches.

Okay, 4 inches, sure. But come on, 4 inches? Like, you think by, you know, The idea that, I think the idea that, you know, 3, 4 inches, for example, if a parent has a couple embryos and they wanna have a taller child based off the embryos they have, I think that is absolutely their right and their choice. And remember, this is really, really important point. DNA is not destiny. So I think when sometimes when we talk about using genetics to predict something like height or IQ, They think you can look at an embryo's DNA and say, that one's gonna be 5'11, right? That's not how it works. Why? Because anything like height, for example, is a mix of nature and nurture.

Absolutely. But Kian, I think we're onto something here. Like, does it not give you pause knowing that within your own family, if your parents had sought to optimize for height, understanding it's not a perfect science and not destiny, if they had done that, potentially someone like yourself would have been overlooked at the embryo stage?

No, I think the thing to remember is that you're really picking an embryo that it's not, you know, the embryos that you have are still based off my mom and my dad's DNA, right? So the embryo's DNA between them, they're not that different between them. It's not like one embryo, for example, is 5 feet and one's like 7 feet, right? That's not how this is. You are picking from basically already existing embryos that are from mom and dad's DNA. So they're combinations already of life.

But let's think about it the other way. What if they were optimizing for intelligence? I have no idea what your brother does. I'm sure he's a bright and interesting guy, all right? But you're running this company, millions of dollars are backing you, okay? You've got something going on upstairs. You exist, but your parents choose against, they choose you, and he ends up not existing. These are real, if a parent is having 1 kid or 2 instead of 3, We are living in a world through this technology where they might choose you, the one who's smarter in the pre-genetic sequencing, than the other one who might be— have other qualities that people value. You see what I mean? Your brother might not exist in this scenario.

It's not— it's really not how I think about it. So I think the thing to remember is there's this idea that— I think there's this idea that like the embryos, for example, are dramatically different from each other. This is a point when you've looked at the chromosomal count, you've identified that's normal, looked at the morphology, you confirm that's normal. And then you basically say, hey, this embryo is going to be 5'8 and this embryo is going to be 5'6. These are not fundamentally different. They're the same DNA from mom, same DNA from dad. But then it gets to a more important point, which is I see it as our job at Nucleus to be very thoughtful, very deliberate in how we present these results to patients. But it is ultimately the result of the couple to say, hey, I want a taller child. Just like, for example, if someone decides, you know what, when I'm on Tinder, I want to pick a 6-foot-tall man because I want my kid to be tall. What, am I going to say, you know, that's not okay? That's their right. That's their choice. In the same way that now— or similarly, right, we make all sorts of decisions that impact our future child, right? When a woman's pregnant, you say, hey, probably shouldn't smoke. Hey, you probably shouldn't drink. Right. Right? These things can negatively impact the development of your child, right? Genetics is just another tool. Even with like growth hormones, right? A parent could say, hey, I want to give my son or daughter growth hormones. I want them to be taller, right? I want to— actually, sometimes people break legs and then extend the bones of their child for them to be taller, right? So in other words, what I'm saying is that genetics is an already existing tool that parents use to help their future child. And I also think one more point on this, which is When you actually talk to parents, right, there's like the theory of this, then there's the on-the-ground level. We are grateful that, you know, we've worked with thousands of families in our genetic testing for adults, right, and embryos. So when you think about this, I think parents view it very pragmatically, which is they have 5, 6 embryos, okay? Already they're going to have to rank, sort, and compare the embryos. Now they have more information to make a more thoughtful and deliberate choice on which one that they want.

Is there any quality that you could genetically test for that you would say, I don't feel comfortable testing for this?

I think currently we provide basically the full range of insight that there is to know on your future child, from both the health perspective and well-being and longevity perspective. As a company, we like to say that parents should build generational health. This idea that you don't just pass down your kind of values, your morals, but you also pass down your DNA. And people can be very deliberate and thoughtful in the way they do that using Nucleus's technology.

So height, weight, personality, intellect— as we get better and better screening for that, you're comfortable with all of those dimensions being part of the test?

We provide them. We provide them openly. We provide them proudly. We think these, you know, These insights, they don't belong behind kind of a dark wall. It's one of those things that, you know, people are still, I think, a little uncomfortable talking about. Our approach is to say, my approach has always been, this exists. This is how it works. This is how you can use it. And to me, I really believe that, you know, sunlight in that way is the best disinfectant. We should put this out in the world because everyone, everyone, no matter where you're from, no matter how you look like, no matter how much money you have, You want to give your child the best start in life, and this technology can help you do that. And it's an expansion on existing technology that we already use to do that. So I think it's a win-win for everyone, for the clinician and for the patient.

You see this as a continuation of what humans already do?

It is. Absolutely. That is the case. Yes.

When we date, we might look for somebody who is tall and smart.

That's what people do. Yeah.

Right. Or a great musician or a great artist or you name it.

Yeah.

So this is a continuation of what we already do when we're dating. And what we already do to some extent before we have kids.

Yes.

And now we're just reaching further down the line.

100%.

This is where it gets super fascinating. Yeah. And my father had schizophrenia.

Really?

It's probably caused by some drug use in his life, although there's some evidence that his father also had schizophrenia. I have not.

Did you ever take a genetic test?

I've taken— not for that specifically. Maybe we'll find out later.

You could, yeah.

But so he has many qualities One aspect of his life is the schizophrenia or the bipolar nature of his life. That's one dimension. Yeah. Would you throw— it's a hard question for any family to think about, and we're getting into philosophy here, but do you throw away that whole life, which includes me and then all of my children, because you're trying to sort out the schizophrenia?

I wanna again restate that of the embryos you're picking, these are embryos from mom and dad's DNA. You're basically picking among siblings. Right? Yeah. And so the idea today already, the idea of like, oh, you throw out this embryo, throw out that embryo, that is done in every IVF clinic in the country and around the world. They take embryos and they'll say, this embryo, for whatever reason, it's the parents. If the parents want to implant an embryo that has the wrong number of chromosomes, for example, they have the right to do that. Parents today mostly choose not to do that. And so similarly, if a parent doesn't want to implant an embryo with breast cancer or diabetes or cancer, That is a, from our perspective I think, a very common sense right of the patient. It is the right of the patient to know that that information exists, that they can get that information, and to choose to use that information. Those things all matter. We're not saying everyone needs to do this or not. What we're saying is you should know it exists, you should know it's a real option, and if you want, you can access it. Anyone.

You used the term genetic optimization earlier. I know other people would say eugenics, right? I know, I know you, I knew you'd have a reaction to that word. That word hangs like a shadow over this whole industry. Tell me what you hear when you hear that term and how you're different.

I think the thing I think about is patients coming to us who used our technology, who identified some sort of hereditary disease risk in their child, And how now, because of the power of Nucleus, they don't have a child with a disease. They don't have a child that, God forbid, had the same fate as my cousin. That's honestly what I hear and think about genetics. I think, I also think about how genetics as an industry is getting cheaper, it's getting more accessible, and it's moving from this idea of kind of ancestry testing, which we had spoken about, like kind of 23andMe and Ancestry were very focused on that. to people understanding DNA as a tool for health, well-being, and building what's called generational health.

So gender, or genetic optimization, is not eugenics because—

By any stretch. Because it's fundamentally about empowering people with information that they can use to give their child the best start in life. It has absolutely nothing to do—

But it is selective breeding based on the idea that you can have a better outcome and that outcomes are not desirable.

The American College of Gynecologists and Obstetricians recommends this sort of screening, carrier screening, preconception screening, in every couple in the country. Right? So the idea that, hey, we shouldn't pass down hereditary disease, I mean, that's— You

know, everybody's with you on the disease part. Totally. Right? Like, I don't think anyone wants suffering.

Remember, we don't— it's not like we take an embryo and we're like, oh, this embryo's height is 5'6. Right? These are one— that's one of 2,000 analyses we provide. So when you ask me about this and you say, oh, you know, intelligence and height, I'm like, yeah, we do that. And yes, if you want 2 inches taller for your child, 3 inches taller, right? If you want a couple IQ point difference, absolutely, by all means do that. But I'm saying what you're really asking me here, you're asking me, what is life about? That's actually what you're trying to get at when you talk about height and IQ, right? They're abstractions of life, right? You're trying to gauge, okay, can I give my child a better start, right? The thing that I think is most important to realize is 2 things. One, because DNA is not destiny, the messiness of life, the nurture element of life, right? How hard your child works, you know, what school they go to, what resources they have, serendipity, all those factors are never ever going to go away. Even if your kid is 2, 3, 4 IQ points or 3 inches taller, these are just little details that also make life. And so I think sometimes people forget that. They want to basically abstract down DNA, abstract down life just to this genetic material. That's the beginning of life. That DNA is not life. DNA is the beginning of life.

Totally. But if life is so messy, then what's the point of any of this?

It's sort of like saying like—

What value is in nucleus if it's all a mess afterwards anyway?

You know, when you make a weather forecast, you know, if I tell you it's gonna snow tomorrow, That's gonna be pretty useful, right?

Yeah.

And by the way, sometimes when the weatherman says that, they say it's gonna be 12 inches, it might be 9 inches, right? But no one's that upset. Why? Because you get prepared for the next day, right? So we make forecasts all the time.

Yeah.

We practice preventive medicine all the time. Nobody wants to get a disease. No one wants to have it so, you know, I've been short my whole life. I've never shared what I'm about to share publicly. You know, my parents at some point said, you're really small. We should take you to the growth hormone doctor to see what's wrong. Yeah. And we went there. I remember they, you know, had these growth charts, and basically I was like dramatically undershot, right? I was probably in like the, you know, whatever, 9th percentile or something. And my parents deliberated, like, you know, should we give him hormones, for example, to be taller? Well, we didn't end up doing that. We decided not to, right? But one has to wonder, right, if, if one wanted to, if a parent wanted to, right, In that way, actually, height became somewhat of, you know, you'd argue a medical issue to some extent, right? It's about development and growth, right? What did my parents want? If my parents wanted, you know, basically me to be a couple inches taller, the emotional, hormonal, physical, expensive cost that would be required 15 years later, 20 years later— Alzheimer's is another great example of this, right? 80 years later, you have neurodegeneration when at the beginning of life you could have noninvasively without any needles, without any surgeries, at the click of a button on software, you could pick an embryo that's healthier or taller? As a parent, I really want you to put yourself in a parent's shoes, right?

I have 4 kids.

You have 4 kids, right? Of course you're gonna want that. Who doesn't want that?

Here's where it gives me pause. Sure. I'm speaking here, but I think I speak for a lot of people. Yeah. When you select an embryo based on your predictions, it's hard to know what you're eliminating at the same time, and it's hard to know because Let's say you're trying to avoid schizophrenia because it ran in my family. Well, schizophrenia has also been found in many great human beings. I

have a very high genetic risk of schizophrenia, actually.

Okay, so like, if you were optimizing against depression, for example, well, there's good evidence that Lincoln had depression, and it might have actually helped him survive some of his difficult— some of the most difficult times in this country's history. So in other words, while you're throwing out schizophrenia or depression, for understandable reasons, you might also be throwing out a complex mix of things that go along with it. And you don't get a Lincoln, and you don't get a Van Gogh, and you don't get my father.

No, no, no, absolutely not. Let me tell you why. Why? Let's say I had kids. I'm high genetic risk for schizophrenia. I'm your example. By the way, a lot of founders I know, they're very high genetic risk for schizophrenia. All right, so that's something interesting, right? If you actually— if you do studies, you can see that High genetic risk for schizophrenia can be associated with like a lot of creativity. Exactly.

Beautiful. Right? So how do you preserve the creativity?

Well, but I'll tell you how. I'm high genetic risk for schizophrenia, right? Even though I'm high genetic risk for schizophrenia, my chance of getting schizophrenia is still really low. So typical population is like 0.4%, I'm probably like 1.5%, right? So even though I'm really high genetic risk, my overall chance is really low, okay? And so let's say I married a girl who also has really high genetic risk for schizophrenia. This is what we have to understand. The embryos are all going to have a high risk for schizophrenia, right? Maybe as a couple I say, look, I want to preserve that. I want to preserve that essence. Maybe I want to preserve that creativity, right? And again, this is part of the importance of genetic counseling and people understanding the complicated way that genetics can manifest. I cannot, because I had a high genetic risk for schizophrenia and my wife has a high genetic risk for schizophrenia, I cannot say, oh, I'm going to make an embryo without a high risk of schizophrenia. This is the thing that I think is very important to understand. You're choosing among embryos that all have high risk because mom and dad are both high risk. Similarly, think about height. Obviously, if, you know, a 6-foot person marries a 6-foot person, the kids are going to be quite tall. Meanwhile, if 2 short people marry, they're not going to be able to have tall kids. So you're not— this is my point, which is you are still passing down the essence of who you are. And now think about the schizophrenia example. I might not want to pick that embryo that is the highest possible schizophrenia risk, right? I might pick one that is maybe medium or low based off of the pool of DNA that I have.

You're saying it's still in there and therefore you're not—

Absolutely.

Getting rid of it completely.

Absolutely. You're not by any means. You can still get exceptional people. But let's be real, exceptional people comes from a lot more than just DNA. I mean, it comes from life. And I mean, nucleus is a creation. You know, it came from extreme hard work, extreme fervor, a level of passion for and personal connection to the problem, right? That didn't come from because, you know, you're born a certain way. I think a lot of the questions you're asking reflect this underlying fear, a fair fear that people have, which is this idea that we're going to start measuring DNA and then start measuring DNA, it's going to be— Determining race. Destiny. From the beginning, there's this idea since the '90s that you look at DNA, it's like, oh, evil man, this is your genetic destiny. That's not how life is.

Well, I think—

That's not how life is. Even if you pick for IQ, even if you pick for height, I'm sure you know many smart people that are miserable. I'm sure you know many short people that are living top of the world. Life is complicated. And so what we do is we don't want to reduce down life in that way. We give you this information and we recognize that it's just one of many tools parents will use. Sending your kid to the best college, trying to, you know, people spend their entire life to do that, for example, right? Giving your kid the best food, right? Making sure your kid's healthy and physically fit. It's just one more tool in a parent's toolkit.

The word hubris comes to mind.

Okay.

Not as an accusation. Sure. But just the idea that we could select embryos better than the chance of the universe, the randomness of it, the holiness of it, depending on one's worldview. Is that not the very definition of hubris?

I think when you go to an IVF clinic today, you have OB-GYNs, you have REIs, they are looking at and appreciating the sacredness of an embryo. Why? Because obviously an embryo comes already from that process, right? You're not changing that process. A sperm is meeting an egg and it's random, right? They're meeting and they're forming life. And then today a doctor will go and say, hey, this embryo is more likely to have Down syndrome, this embryo isn't, for example. And they'll give the choice to the parents. The parents will say, okay, I want an embryo, for example, that is chromosomally normal, right? That I think is actually using the wonders of technology, which we use every day, to improve a process that already exists. And so I really see it as an augmentation, as an improvement of what we already do today, every day in IVF.

How accurate are these predictions?

The way to understand genetic prediction is that certain traits are more genetic, certain traits are less genetic. For example, height. Scientists estimate height is about 80% genetic. Okay. Meanwhile, something like depression, about like 10%, much less. So even if you built the best genetic model in the world to predict depression, right, there'd still be a lot of stochasticity and error. Of course there would be, right, because you haven't modeled life. You haven't modeled the nurture, right? Who are their parents? How are they raised? You know, what are they taught? What are their values? You know, who are their friends growing up, right? And so the question of accuracy always comes down to how genetic is the thing. The more genetic the thing, The tighter the error bars, the better the forecast, the more certain I am that there's gonna be 7 inches of snow tomorrow, right? But most things, even height, height's the most genetic thing you can probably think of, right, besides hereditary diseases, but in terms of common traits you think of, height is still 80% genetic.

What about intelligence? Because that is the one— obviously the world is getting only more complex. It would be helpful for everyone's kids to be even smarter and smarter and smarter. Every parent was thinking to themselves, I want my kid to do well in school and get ahead in life, right?

Yeah, yeah, absolutely.

How genetic is intelligence? How accurate are your predictions, do you think?

It's about 50% genetic. You can probably today explain about 20% of that, 25% of that. In other words, you can get probably around 8 to 9 IQ points in your child. And so you can think of it as almost like very similar to Actually, I think it was during the mid-20th century, they started putting iodide in salt, and then the entire population's IQ actually increased because of just an environmental thing, because people had more access to resources. Like after the Industrial Revolution too, you had people grow about— Persians, speaking of height— around 7 inches. Hmm. Because they had more access to food, et cetera. Right? So my point is, even if you do try to measure, right, like something like IQ, Which we measure every day. SATs, grades, and IQ is also one part of what makes a life a life. We all know that. But all those asterisks aside, you can expect around 8 to 9 IQ points.

And what's the evidence to support these claims? Are you planning on tracking people long-term? Have you already? How do you even know that these predictions, which are so very new, are any good at all?

Well, these models are trained and validated in millions Millions of people. So let's think about height, for example. Yeah, let me explain. It's actually very interesting. So height, if you think about it, right? Let's say I took a large population of people. Let's say I took half a million people. Okay. Let's say I read the DNA. Remember, the DNA that I read in an adult is the same as an embryo, right? That embryo DNA divides, right? And it stays the same during your entire life. It's called germline DNA. Yeah. Okay. So I read DNA in an adult. Let's say I cover their actual height, right? So I don't know what their actual height is, I just read their DNA. I then make a prediction based off their DNA, right? Which again is the same as an embryo's DNA, because it doesn't change your entire life. Yeah. And I say, okay, based off my model, I predict this person to be 5'8. And then I take my prediction, 5'8, and I compare it to their actual one. I say, oh, they're 5'9. Okay, that's how you do it. So you can actually validate the models in millions of people in large biobanks where there's both genetic data and And phenotypic data, things like height and disease risk.

Interesting. So that's true for height, that's true for hair color, eye color.

Eye color, you know, disease, Alzheimer's, diabetes. We actually announced— yeah.

What about this more far-flung stuff like depression, anxiety, acne, intelligence?

Well, yeah, it matters how genetic are those things, but you can follow the same logic for any of these.

But has that been validated in a similar way?

Yeah, exactly. like breast cancer, for example, or heart disease, coronary heart disease. What you do is you say, okay, like, think about it more intuitively, like, how would you do it? You would say, okay, let me get a bunch of people with heart disease, put them in a group, and put a lot of people without heart disease. Let me do my best to account for other variables. And then you find that there are genetic markers that are basically disproportionately found in the heart disease group. Hmm. Okay, and then you can build a model, and then you can give everyone kind of like this basically like a score, and you can say, oh, these people are actually more likely, and you can actually test this model. So, sorry, I'm getting into a little bit of the weeds here. I don't know.

No, no, I get it.

I know this makes sense. And then you find the associations, and then you take another group of people, not the ones that you trained in. You take another group of people who are a mix of heart cancer or heart disease risk or not, and you basically test the model to see how well can it distinguish between someone who's more likely to to get heart disease versus someone who's less likely. And then you can see how good it is. And you measure how good it is compared to the theoretical, basically, maximum genetic effect. Sorry, I'm getting into the weeds here.

No, no, this makes sense. But so you've done this for intelligence by what, tracking grade reached or educational attainment?

These are large public biobanks. So actually, if you look at UK Biobank, right? These are government, actually. They have these large biobanks that scientists can access, and they can do these sort of studies. So the United States has the All of Us. There's a lot of other ones as well that you can actually use to basically, yeah, get information on everything from cancer or height or intelligence. They do a lot of different intelligence tests, and sometimes people use different proxies for it as well. That's how you do it, yeah.

So you feel confident in these predictions? Oh,

absolutely. I mean, we just published a paper yesterday that we showed that our predictors can better predict longevity from an embryo's DNA than any other genetic model ever built. That model was trained and validated in about 1.5 million people. And so, we're very confident, and we released actually a white paper on it as well for the scientists listening, and they can check it out and read it. Okay. It's great. It actually shows that not just you can stratify in a population. But you can actually show between siblings, right? So like my brother and I, right, you can actually see that my brother genetically is predicted to be taller, right? Which he is. Okay, so like that's like a good way of thinking about it.

Okay, so you think this works. The other criticism people have is it's expensive, it's limited to the elites, and it's going to deepen inequality. To that you say what?

I would say the opposite is true in that The fundamental mission of a business like Nucleus is to make sure this technology is accessible to everybody. And we've seen that already. It used to be $1 billion to do this genetic test. Now it's a couple hundred dollars. The price is going to keep getting cheaper. IVF is going to keep getting more accessible. And the purpose of a startup, the lifeblood of Nucleus, why I made Nucleus, is to bring the technology to everybody. Right. The fact that we can have this conversation right now on CBS. I tell you, 6 years ago I was in my bedroom. I'd come across these papers and I would say, how is it possible that we can predict everything from cancer to Alzheimer's to IQ from DNA? From DNA, from just A, T, C, and Gs, that we can predict these things and nobody in the world knows about it? And now we're on CBS, we're telling the world about it. That's beautiful. And that is part of our mission, that's part of my personal mission, to make sure everyone, one, knows about this technology. Right, because a lot of people don't even know it exists. And then once they're educated and informed about it, they can choose to access it and use it to help give their child the best start in life.

But you've got some big financial backers, Peter Thiel's Founders Fund, Alexis Ohanian's investment firm. They're expecting to make a profit, right? So how is it for everybody if it's really part of the marketplace?

Well, I mean, think about the iPhone, right? It used to be in a very small number of people's hands. Nobody had a smartphone. It was like investment bankers in New York, right? Now I look around, everyone has a smartphone, right? You can actually see that a lot with technology. Technology gets cheaper, it gets more accessible, and it gets more accessible because there's investment. I mean, the Human Genome Project, it cost $2-3 billion. Now today we can do that for a couple hundred dollars.

So take me into the future. You imagine as a standard thing, a baby will be born— let's say this way— a baby will be born, it'll get a little baby box at the hospital with some Some diapers and some wipes and maybe a little hat and a little, like, a wrap. Like, there'll be supplies after birth, and before, everybody will do this?

I think everyone should know that it exists, that it's an option, and if they want, they can choose to use GeneX to give their child the best start in life.

How many people have done this so far?

Well, between our adult and embryo product, we've had thousands of— we've helped thousands of families. But remember that the IVF Plus partners we work with, they've helped thousands and thousands of families have children for years. What we do is that we are this kind of end-to-end IVF process and we give you a little bit more information in each of your embryos. You're not changing the IVF process. It's not like, oh, with this new technology you have to do a whole new IVF technique. It's the same thing. It's the same thing that's done in every clinic in every country, but now you get a little bit more information in your embryos.

One of the major medical bodies has said that this is moving, and I'll quote them directly here, Too fast and with too little evidence. Do they have a point?

I would encourage that body to review the most recent research that actually Nucleus produced and other entities in the space produced. I think you're seeing now this kind of prediction. 10 years ago, that was a fair thing to say, right? Actually, one of the bodies, when they cited the idea that these things are moving too fast, they were using models that were, you know, 4, 5, 6 years old, right? But just like with kind of AI models, you know, they get better and better and better and better. And people are starting to be like, oh, these things are getting kind of smarter, right? In the same way, genetic prediction models are getting better and better and better and better. And today, to say that they work and that we've shown publicly that they work, I think that's a very, very fair statement. In fact, we are the only company To have actually open-weighted our model. Think about that. Any researcher, any physician, any academic body, any American institute, they can go and see every single detail into our model, and they can independently test it. That is what we stand for as a business. We stand for openness, we stand for transparency, and we stand for access for everybody.

So, Kian, what does this cost? What do you get for it?

So we provide something called IVF Plus. So there's 2 ways of doing IVF today. You can do IVF, which is focused on having a baby, or you could do IVF Plus, which is focused on you having your best baby. Okay, whatever that means to you. Yeah. And so IVF Plus is actually an end-to-end IVF process that is powered by the most advanced genetic technology. So it's actually not all that much more expensive than regular old IVF. It starts at $30,000. $30,000 for, to be very clear, the cycle, the medications, the consults, the implantation of the embryo, everything, and the genetic testing and the analysis. So you go to an IVF clinic, they'll usually be like, oh, a cycle is $20,000. They won't break up all the other costs. We want to make things very easy and seamless for patients. So we have one price that includes everything from the genetic testing to the cycle. It's $30,000. It starts at $30,000.

IVF Plus. You use the term your best baby.

Whatever that means to you.

Whatever that means to you. I have to key on that phrase because people will hear it, and they'll think, wait a minute, all babies are precious, equally precious. You can't rank the preciousness of them. So the idea of best is just hard to integrate into the idea that we're all created in the eyes of God, or created equal, or you name it depending on your worldview. You know what I mean?

Yeah.

So best baby? What does that even mean?

One time what we did with patients is we showed them about 8 different embryos, okay? And there was about like, I think like 20 people or so. And we asked each of them to pick the embryo that they would pick, right? Just to start understanding how it works and everything. And what was most amazing to me is that the most votes an embryo got was 3. In other words, Each person, depending on their values, what they prioritized, chose differently. Why? Someone else— someone had a history of breast cancer. They, God forbid, saw their mother suffer. Someone else saw their grandfather die of Alzheimer's. Someone else was really, really annoyed that, you know, they were 5'7 and they wanted to be 6 feet. Whatever it was, people ended up picking differently based off of their values. And that's what you're going to find because— Life, again, it's not saying like this is better, this is worse, right? Optimization, the idea of genetic optimization, what is optimal to someone else might not be optimal to yet another person.

Well, but come on now.

There is no— no, there is no— there is no— you cannot say, oh, this thing is better than this. It's just not the case. If you talk to a deaf couple, right, a deaf couple might say, I want our son or daughter to be deaf. Is that a choice you would make? Is that a choice someone else would make? I don't know, but it's their right and that's their choice, and to them, that is what's best. That's the kind of life that they choose to live.

Right, but no one's gonna sit there and choose, I want a short, acne-prone, anxiety-ridden person with bad eyesight and no ability in sports.

Well, similarly today, people are gonna say, hey, as a parent, in every IVF clinic in the country, they will say, you know, I don't want a baby with cystic fibrosis. I don't want a baby with Down syndrome. And in the same way, that's their choice, right? They rank embryos on morphology. They say, hey, this embryo is better to implant than this embryo. That's not something that Nucleus has created. That exists and is done. Hundreds of thousands of babies are born in IVF. IVF itself used to be test tube babies. It was quite stigmatized. Yeah. But now it's common practice. Do you imagine—

There's a lesson in there. Do you imagine a future though where short people, acne-prone people, anxious people are genetically tested out of existence?

No, because again, you have to understand what we're doing. Which is, 2 short people—

Every generation though, if you choose the least likely outcome—

No, but even so—

Over time, no?

Even so, you mix up the DNA, people are— what's gonna happen is, people are going to, like, again, if short people marry each other, right, if you really wanna have a tall kid, right, you're gonna marry someone that's tall, right? That's been true forever. Short people are gonna marry each other because, you know, they're gonna be the same height, whatever, and then they're gonna— their choice, their outcome space is gonna be smaller, right? So, this isn't— you're not changing the DNA. the randomness of DNA will still happen, right? You're not changing anything. You cannot go outside the scope of where already mom and dad creates the clay, for example, of the possibilities. So—

So optimization over time will not reduce certain classes of human beings out of existence? No,

absolutely not.

Okay. You, when you launched the company and were online, You spent hours in that initial day batting off various accusations, criticisms, assumptions. And there was a moment where you have a whole company to run, you have a lot of science to digest, but you were engaged online with the critics.

On Twitter.

On Twitter. And you got lots of impressions. It was a big viral thing. I think you later said you got 5 million impressions, right? What was the criticism? You think you won the argument?

No, there's no winning the argument here, okay? Because what's important for us is to educate people about what the possibilities are and what exists, and then let people decide for themselves whether they want to engage with that tech or not. It's not I'm right, you're wrong. If somebody doesn't want to engage with the technology, by all means, that's their choice. I think one of the most important things is that we maintain that reproductive autonomy. While also, if you choose to engage with the more advanced tech, being very deliberate and thoughtful in the way we communicate. You know, on Twitter, one thing that definitely came up is, and I believe this, I think Nucleus believes this, and I think eventually this will be clear, which is genetics is the single greatest preventative medicine tool that has ever existed. Why? You have millions of babies born around the world with severe genetic diseases. You have hereditary cancers. I gave the Angelina Jolie example. Right? Where if Angelina Jolie went and did IVF, she may have, without knowing about the BRCA variant, assuming she didn't know about it, she would have inadvertently passed down a hereditary disease risk to her daughter. I don't think that as how things are is acceptable. And I think at the very least patients should know the technology and information that exists out there. They should know it works. They should know it's reliable. And they should know that they can access it. That's what to me what this is really about. Thank you.

$30,000? Is that what it costs?

Yes, but remember that I— so the actual genetic testing part is a very actually small part of that. IVF itself, you know, a typical cycle can be $20,000. And so when I say $30,000, I'm not just talking about the cycle. I want to be very clear, $30,000 is actually a very, very good price for an end-to-end IVF process from initial consultation all the way to pregnancy. It covers everything: medications, cycles, consults, the genetic testing of the embryos, the analysis of the embryos, AMH testing, blood testing. So we've actually already, as a company— some companies, they'll charge, you know, a lot of— $40,000 just for the genetics. That's not how we do it. We keep things cheap because we can do things at a higher scale because we've been around longer. And so we as a company really, really, really important to me. I cannot even tell you this. Like, when I, when I was in my bedroom and I was building Nucleus, remember probably the only genetics company started in a bedroom in history. And I was thinking how the software that you were building, the wonder of software is that it can be ubiquitous, right? Anyone can go on their smartphone, anyone can open up their computer now, and they can access something like Nucleus, you know, IVF, right? Like, that's kind of an amazing thing to me, which is like the fact that you're applying this sort of beauty of the kind of iterability and accessibility and reach of software But it's something that is so consequential and as important as life itself.

Take me into the future.

Yeah.

Where do you see Nucleus going?

I think you are going to see every person and every, probably every, so there's a couple ways to think about this, right? Because genetics as a tool helps both adults that are alive and well, Helps people live longer, healthier lives, identifying risk, also helps the next generation. So we call it generational health. I think as a company, we think that everyone in the world will be building generational health. What does that actually mean? That means that they're gonna have the ability to not pass down disease risk burden, right? Not pass down cancers, not pass down rare genetic diseases. You're gonna have a child born who won't have the same fate as my cousin had, right? And it also means that parents will have the right to choose, and they're gonna find that you're gonna come across the same messiness of life when you do this. You're gonna be able to choose height, even IQ, or eye color, right? That's gonna happen. They're gonna have the right to do that, and it's gonna be something that, just like with IVF, at first it was somewhat stigmatized. Now it's how 1 in 50 babies in the United States are born. It's gonna be the same evolutionary process. And people are going to, I think, realize that in diving deep into the language of life, in diving deep into what it is and what it can tell you, you can also realize its limitations. And that, I think, will be the most important lesson for us.

I imagine, and you tell me if I'm right, that the biggest risk for Nucleus is a law in Congress that says, thou shalt not test for these things in embryos. Thou shalt not play God with our future.

Well, to be clear, there are already regulations, right? Embryo testing is regulated. Genetic testing is regulated. Nucleus is an informatics laboratory. We're CLIA certified. We're CAP accredited. So these things are regulated.

But there's no limitation presently on any of these predictive genetic tests.

No, there is actually oversight over this.

So what's illegal then?

What's illegal?

Yeah, what couldn't you test for?

Well, the thing to remember is that, you know, as an informatics laboratory, right, Nucleus is actually a medical laboratory, we're able to provide patients with the disease analyses. It's called, more technically, it's called PGT testing, basically, right? So there's PGT testing that's done, and then we analyze the data.

Preimplantation genetic testing.

Yeah, exactly. So it is regulated. And again, it's done in hundreds of thousands of embryos every day.

I guess what I'm asking you is, are you concerned, and I imagine you would be, that Congress will come along and say, we don't feel comfortable with any private company testing for, say, intelligence?

I think that ultimately what it comes down to is the patients are going to be able to determine what they want to select in their future children. And I think what's going to be important is that anyone, anywhere should be able to have that choice.

So genetic counseling, how does this work after the sequencing and the review? Do I get just sort of a piece of paper with results? You guide me? What happens?

Yeah, so we provide patients with basically the software platform, which we can show you. You have your embryos, there's their sex, there's information on the embryos. And we also assign you a genetic counselor, we call an IVF Plus counselor, and they actually can walk you through all the results. They can walk you through the implications, how to understand the results. Because doing great science is obviously critically important, but just as important is meeting the patient where they are. Because patients, they don't come from a genetics background, they don't know, they don't understand R-squareds and the intricacies of the models. So by having a genetic counselor walk through, you bring that patient empathy meeting the data. And so that's really important to communicate, which is anyone doing IVF+ has an IVF+ counselor that walks them through the entire IVF process, which by the way, genetics is a small part of that. And then when you actually get your embryo results, they can help guide and inform you and help you understand the results alongside the software itself. We're very careful in the way we design the software. We want it to be kind of beautiful and thoughtful. But of course, there's always that person there to answer any questions.

So someone's gonna come along and be like, this embryo here, that's your homecoming king.

No, no.

This one over here though, total dunce. Total dunce. Night school all the way. Forget about it. Behavior problem, mental health issue. This one over here though, nerdy, but gonna go far. Yeah. This is a promising one.

I wish DNA could do that.

No?

DNA cannot do that. DNA's never— DNA can't tell you stuff like that. You, you are talking about things that only life itself, nurture, your environment, your parents, that's gonna determine that. You can't look at an embryo and be like, oh, yep, that's the one. No, you're gonna see. I'll show you the software. I think it will ground things quite a bit.

All right, cool.

All right.