#46 - Ending The Genetic Lottery | Noor Siddiqui, CEO Orchid

Summary

Noor Siddiqui, founder and CEO of Orchid, discusses how her company is revolutionizing embryo screening by providing parents with whole genome reports on their embryos during IVF. Unlike traditional screening that only examines 1% of the genome through morphology assessment, Orchid provides 99% genome coverage, allowing parents to screen for thousands of genetic diseases including pediatric cancers, birth defects, neurodevelopmental disorders, and complex conditions like heart disease and schizophrenia.

The interview was conducted at a baby shower for one of the “Orchid babies” near the Golden Gate Bridge. Siddiqui shares statistics about the prevalence of genetic disease: 25% of NICU infant deaths are genetic, 60% of moderate to severe intellectual disability has genetic causes, and 10% of Americans (30 million people) have a rare genetic disease. She emphasizes that the main barrier to adoption is knowledge, not cost, since families already paying $30,000 for IVF often find the $2,500 per embryo screening fee manageable.

Siddiqui also addresses the historical moral panic surrounding every reproductive technology from condoms to IVF, predicting that embryo screening will become as normalized as birth control. She discusses how the first embryos screened were her own, and how patient demand has driven adoption, with patients literally refusing to use IVF centers that didn’t offer Orchid, leading to over 100 clinics now being onboarded through patient-led recruitment.

Highlights

”Midway through pregnancy you find out this baby doesn’t have a skull - it’s extremely traumatic”

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“A pregnancy is an extremely intense thing. You’re metabolically running a marathon every single day for 9 months. The idea that midway through that process, you find out that this baby doesn’t have a skull, isn’t going to come to term - it’s extremely traumatic.” — Noor Siddiqui, 0:00

”25% of NICU infant deaths are genetic, 95% of rare diseases have no treatment”

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“25% of infant deaths in the NICU are due to genetic disease. 60% of moderate to severe intellectual disability is genetic. 50% of miscarriages are genetic. And 95% of rare genetic diseases have no treatment, let alone a cure.” — Noor Siddiqui, 5:29

”The genetic lottery is incredibly unfair - now you can make it more equal”

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“The genetic lottery is incredibly unfair. Now you finally have this ability to make it more equal and more fair for everyone. For the first time, parents can genetically bless their child.” — Noor Siddiqui, 10:59

”We have more data going into shoe buying than the biggest parenting decision - your child’s genome”

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“We have more data going into where you go for lunch, what shoes you’re going to buy, all these super trivial decisions, than the biggest parenting decision you’ll ever make - your child’s genome.” — Noor Siddiqui, 12:43

”Two Supreme Court cases were required just for women to get condoms”

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“There were two different Supreme Court cases fought over condoms. The first was so married women could get access, the second so unmarried women could. Previously they were banned under obscenity laws. Every reproductive technology faces moral panic.” — Noor Siddiqui, 40:03

”70-80 of our 100+ clinics were recruited by patient demand”

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“We’re in over 100 IVF centers now. 70-80 of those were recruited through patient demand - patients literally refused to use centers that didn’t offer Orchid. The first embryos we screened were my own.” — Noor Siddiqui, 32:42

Key Points

• Whole Genome Screening (0:34) - Orchid provides 99% genome coverage vs traditional 1%, allowing screening for thousands of diseases that were previously missed
• Morphology Beauty Contest (1:06) - Current embryo selection relies on visual grading under microscope; studies show rotating images produces different grades from same embryologists
• Genetic Risk Scores (2:10) - Can quantify genetic risk percentiles for complex diseases like heart disease and schizophrenia, not just single-gene conditions
• 25% NICU Deaths Genetic (5:29) - A quarter of infant deaths in neonatal intensive care units are due to genetic disease
• 50% of Miscarriages Genetic (5:42) - Half of all miscarriages have genetic causes
• 30 Million Americans Affected (6:32) - 10% of the US population has a rare genetic disease, and 80% of rare diseases are genetic
• 25% of ER Visits Under 40 (6:51) - A quarter of non-traumatic ER visits for adults under 40 are for genetic reasons
• 95% of Rare Disease Untreatable (7:51) - 95% of rare genetic diseases have no treatment, let alone a cure
• Copenhagen at 10% IVF (29:00) - Nearly 10% of births in Copenhagen are through IVF due to government subsidization, vs 2.5% in the US
• $30K US vs $5K Europe IVF (14:52) - IVF costs $30,000 in the US but only $5,000 in Europe, and is often fully covered there
• $2,500 Per Embryo Screening (14:20) - Orchid screening costs $2,500 per embryo
• South Asians 2x Heart Disease Risk (17:44) - South Asians get heart attacks 10 years earlier and are twice as likely to die than other ancestries
• 30-80% Risk Reduction (18:30) - Embryo screening can reduce relative genetic risk by 30-80% for conditions like heart disease
• Sex Selection Legal in US (21:10) - Sex selection during IVF became common in US for “family balancing” but remains banned in India and China
• Over 100 IVF Centers (32:42) - Orchid is now in over 100 IVF centers, with 70-80 recruited through patient demand
• First Customer Was Herself (35:10) - Siddiqui’s own embryos were the first screened at Orchid’s lab
• Luxturna Gene Therapy $2M (52:30) - Gene therapy for her mom’s blindness condition costs over $1M per eye and only prevents progression, doesn’t reverse it
• Condom Supreme Court Cases (40:14) - Two separate Supreme Court cases were required to give women access to condoms (1965 for married, 1972 for unmarried)
• Epidurals Faced Moral Panic (43:15) - Pain relief during childbirth was controversial because some believed women should suffer due to Eve’s fall from grace

Mentions

Companies

• Orchid (0:29) - Noor Siddiqui’s company providing whole genome embryo screening
• Stanford (36:10) - Where Siddiqui did AI research and stumbled into genomics, and where her first embryos were screened
• United Healthcare (33:20) - Example of bureaucratic insurance approval process limiting patient access

Products & Technologies

• IVF (0:50) - In vitro fertilization, creates multiple embryos for selection
• Whole Genome Sequencing (0:43) - Technology providing 99% genome coverage for embryo analysis
• Genetic Risk Scores (2:06) - Models that quantify disease risk based on many genetic variants
• IVG (In Vitro Gametogenesis) (37:59) - Making egg cells from skin cells, an emerging technology
• Luxturna (52:18) - First approved gene therapy in US for RP65 variant of retinitis pigmentosa, costs $1M+ per eye
• Morphology Grading (1:08) - Traditional embryo selection method based on visual appearance under microscope

People

• Noor Siddiqui (0:24) - Founder and CEO of Orchid, economist and molecular biologist background
• Astra (3:14) - One of the Orchid babies whose baby shower was the interview location
• Noor’s Mom (7:08) - Started going blind in her 30s due to genetic condition (retinitis pigmentosa)
• Trump (16:28) - Referenced for claiming to be “father of IVF” and embracing the technology politically
• Jeff Bezos (56:42) - His mom’s quote about him being unable to stay unhappy for more than 5 minutes

Surprising Quotes

“A pregnancy is an extremely intense thing, right? Like you’re metabolically running a marathon every single day for 9 months to create this human inside of you. The idea that midway through that process, you find out that this baby doesn’t have a skull, isn’t going to be able to come to term, like it’s extremely traumatic.” — 0:00

“The genetic lottery is incredibly unfair. Now you finally have this ability to make it more equal and more fair for everyone.” — 10:59

“We have more data going into where you go for lunch, what shoes you’re going to buy, all these super trivial decisions, than the biggest parenting decision you’ll ever make - your child’s genome.” — 12:43

“There was actually two different Supreme Court cases that were fought over condoms. The first was so that married women could get access to condoms and the second was so that unmarried women could get access to condoms. Previously they were banned under obscenity laws.” — 40:03

“Every hardship is an opportunity. Anything that’s like really hard to do just ends up being like a really good story later. So, it’s not really a hardship, right? It’s almost just like a cool story.” — 56:48

Transcript

0:00 A pregnancy is an extremely intense thing, right? Like you’re metabolically running a marathon every single day for 9 months to create this human inside of you. The idea that midway through that process, you find out that this baby doesn’t have a skull, isn’t going to be able to come to term, like it’s extremely traumatic. For the first time ever, parents have this ability to help them avoid a whole category of disease that previously was left entirely to chance.

0:24 This is Noor Siddiqui and she is the founder of Orchid. Do you want to just do a quick description on what is Orchid? Yeah. So, what Orchid helps parents do is it helps them protect their baby before they’re even born. And the way that we do that is that we help parents get whole genome reports on their embryos.

0:46 So what does that actually mean? When people go through IVF, they make multiple embryos. And when they make those multiple embryos in the IVF center, that decision of which embryo to transfer is currently made almost blind, right? So they have extremely limited information. About 1% of the genome and they usually do this sort of beauty contest where they look at the embryo under a microscope and they say based on the morphology or how does it look under their microscope, they choose which embryo to transfer.

1:16 So what Orchid does is it completely changes that. It upgrades the amount of information that parents get access to. Instead of that 1% of the genome they get 99%, which means they get a hundred times the data. They can scan for thousands of diseases that previous technology completely missed. And it allows them to make a more informed decision going into their pregnancy and avoid diseases like pediatric cancers, adult onset cancers, birth defects, neurodevelopmental disorders, genetic forms of autism, more genetically complex diseases where it’s not just driven by a single monogenic condition, but things that are driven by the cumulative impact of many millions of genetic variants.

2:00 Things like celiac disease, things like heart disease, schizophrenia, bipolar. You can also look at genetic risk scores for those diseases and then quantify the genetic risk of each embryo. You can see, okay, this embryo is the 99th percentile of risk versus this embryo in the 50th percentile of risk. So what parents are able to do is they’re able to move the genetic risk of their embryos, which previously, for you and I is an immovable risk factor.

2:30 Like you have this decision in life of do I want to smoke or do I not want to smoke, great that drastically changes your health trajectory but our genetics, our genetic risk is fixed. So what’s really powerful about this tool is that for the first time ever parents have this ability to genetically bless their child, help them avoid a whole category of disease that previously was left entirely to chance. So yeah it’s really exciting for parents to be already using these tools today to mitigate the disease that they’re most concerned about for their family.

3:01 Do you want to talk about where we are and like the baby shower today? Yeah. So today we’re by the amazing Golden Gate Bridge. We have an amazing water view and it’s in honor of Astra, one of the orchid babies that was born and it was just amazing to get the entire community surrounding the parents and the new baby. And there’s some other orchid babies that are in San Francisco that got to attend.

3:29 So, yeah, it’s just really I think unfortunately unusual to be surrounded by a bunch of babies in San Francisco, but we made it happen. So, it was great. I thought there was this was more babies than I’ve seen like in close proximity ever in San Francisco, which is nice. I know. I got a lot of texts about it being like, whoa, this is like I haven’t seen this many babies in a while. So yeah, it was fun.

3:54 And I think it’s a little bit babies are a little bit mimetic, you know? I think like once you see one, you’re like, “Oh my gosh, they’re so cute.” And then people get excited for them. So I think babies beget more babies. Yeah, they’re an incredible sales force. Yeah. No, they are just incredibly cute. So there’s a lot of people who are like recently engaged who are like, you know, wow. Okay, I see. They might have been putting it off before, but they might be more excited about it after they saw just how cute they are.

4:22 I know that for like my own personal family, we have a whole bunch of like random genetic conditions and I’m kind of… What’s going on in your family? Tell me more. We’ve got celiac disease, my sister and dad. And then we have arthritis, gout, a number of other autoimmune problems and like all that stuff. What was that like for you guys growing up? Not a bunch of tasty food in the house. Yeah. Yeah, cuz there was no gluten and so you were and then they were also vegetarian so that was not awesome.

4:52 Did it take a while for them to get diagnosed or was it like a… My sister I think it was like a number of years and so she would just like cough all night. Oh wow. For like the first five or six years of her life I believe. Wow. So it like affected her sleep too. Yeah. Yeah. It was not great. Not optimal.

5:06 I would be curious how do parents feel cuz this is one of those things where you take the test I believe and figure out what all might be a problem. How do people react when they kind of realize how many things could go wrong? Yeah, I think people are honestly pretty surprised by how much is genetic. So I think kind of just some of the facts and figures here, right?

5:29 25% of infant deaths in the NICU neonatal intensive care unit are due to genetic disease, right? 60% of moderate to severe intellectual disability is due to a genetic cause. 50% of miscarriages are due to a genetic cause. So I think that nobody realizes how large these numbers are. And I think that it’s honestly a little bit hard to keep up right because every single year people are cataloging more and more genetic diseases. So whatever the number was last year, it’s going to be slightly higher.

6:00 How many kids is that in like the NICU? Like how many people… So 25% die because of genetic disease. How many is that? Is that like a thousand a year or… I don’t know the exact absolute number that study is citing. I think it’s like an aggregate of maybe 10 or 15 NICUs around the country. Because obviously the aggregate number is pretty hard to find. But basically in the entire US about the best estimates are 10% of the population has a rare genetic disease. So it’s about 30 million Americans.

6:32 But obviously it’s a very small subset or infant death, right? Obviously that’s like the most severe category. Another really interesting stat I think is that about 25% of people who are in the ER as adults who are there for a non-traumatic injury, right? So who aren’t there for a car crash under 40, the reason why they’re there ends up being for a genetic reason. So it’s crazy, right? Like people have these sort of ticking time bombs and they occur at a random time.

7:05 For my mom, she started going blind in her 30s, right? And that was a sort of a genetic ticking time bomb. And then for these folks who end up in the ER, their heart stops suddenly, right? And they thought it’s the heat, but it’s actually a cardiac condition that’s underlying all of that. So yeah, I think it’s really surprising just how it’s a double digit percentage.

7:35 What’s crazy is that’s like 10% of US adults, right? For 30 million Americans having a genetic disease. Having a rare disease and the vast majority of those are genetics. About 80% of rare disease is genetic and then half of those affected are children. So that’s the other thing that’s crazy is that 95% of rare disease that is predominantly genetic does not have a treatment. Right? So it’s not only is there not a cure, but there’s not even a treatment 95% of the time.

8:05 So basically there’s these thousands of different genetic diseases that we’ve cataloged but individually they’re extremely rare but in aggregate they end up being quite common. But it’s really interesting that you mentioned celiac disease specifically because that’s actually one that people really commonly diminish. And I think that that’s really unfair, right? Because if you’re not living with the condition, it’s really hard to be judgmental about it.

8:30 People say, “Oh, Alzheimer’s, well, that doesn’t affect you till you’re older.” Well, it’s like, okay, are you a caregiver for a parent with Alzheimer’s? Do you know what it’s like to lose your memory? Right? And same for celiac. Like, oh, you know, you just avoid gluten. It’s like, okay, well, have you actually talked to someone with celiac disease? What it’s like? Do they want their child to have it? Do they want their loved ones to have it if they can avoid it?

8:51 It’s like every restaurant that you go into, it’s like rolling the dice on if they actually clean the kitchen and put on different gloves and stuff when you’re making food. Yeah. Exactly. There’s no way to monitor them. And then it impacts your life. So then if you accidentally… It’s not even an accident, right? Someone told you that it’s going to be fine, but then in reality it wasn’t. And then now, okay, you’re messed up for the next two days. Like, it’s not fun to have that kind of uncertainty.

9:15 How fast do you think, like, personally, I’m going to immediately adopt this. And I think most of the people that I interact with will. But how fast do you think that it’s just going to be like when will the last baby that’s not pre-screened be born is your guess?

9:30 Oh, I think there’s actually always going to be babies that are going to be born the old-fashioned way. Think about smartphones today. Smartphones are probably one of the most widely spread technology, right? There’s like billions of smartphones out there, but it’s still not everyone has one, right? So, yeah, I think when it comes to something like babies, right now over 50% of births are accidental. People are not planning their pregnancy and they get pregnant anyways.

9:58 So I think that’ll continue to happen. But I think that the fraction of births that are going to become intentional and that are through Orchid where people are going to actually prioritize maximizing their child’s genetic health and they want their child to be genetically blessed, I think that is going to become increasingly more common. Fetal alcohol syndrome has gone down since we now know that it’s a condition. Like don’t drink when you’re pregnant. Yeah. Yeah. Crazy.

10:25 I mean, people used to drink when they were pregnant. They didn’t know, right? So, now that we know that leads to poor outcomes for infants, people stopped doing it, right? So, I think it’s the same kind of thing. Now, this new capability for humanity got unlocked, which is that before you had to roll the dice and just get a random outcome. Are you going to have genetics that allow you to live until you’re 90 or are you going to have genetics that are going to literally kill you before your first birthday?

10:55 The genetic lottery is incredibly unfair and now you finally have this ability to make it more equal and more fair for everyone. Everyone gets to start at the same place, right? Being able to just have all your limbs, have your vision, have your hearing. I think it’s really easy for people to take that for granted because a lot of the people that you interact with are sighted, can hear, don’t have a developmental delay.

11:25 But there’s this huge fraction of people, millions of parents, who have children who are never going to be able to live independently, who are never going to be able to meet developmental milestones like being able to walk, being able to talk, being able to read a book or speak. There’s children who are non-verbal and it’s normally through no fault of their own. They just literally have broken genes that don’t allow their brain to form, their spinal cord to form, their skeleton to form.

11:55 Like that’s incredibly unfair and it’s cruel and we have nothing to fix it or to help those families. And I think that I feel really honored to be able to help families who’ve had really catastrophic outcomes be able to now plan for their next child to be healthy and have a normal life.

12:15 And I think that for the vast majority of families who are thinking about the biggest moment in their life, I think when people talk about their lives, having kids is probably the top one or maybe the top life experience. Top three life experience right so it’s like… The idea that we have more data going into where do you go for lunch, what shoes you’re going to buy, all these super trivial decisions is insane.

12:45 You’re optimizing so many things in life and then you just forget the entire big one. Yeah. Yeah. Exactly. It’s like Pennywise or pound foolish, right? So it’s like we’re constantly ingesting massive amounts of data over things that are completely frivolous and irrelevant like skin care or lunch or what song we should listen to, right?

13:10 Versus I think the biggest impact on your child’s health is going to be their genome, right? The biggest impact on their health trajectory is do they get pediatric cancer or not versus the things that people agonize over which is like what color should I paint my nursery, do I want organic food or processed food, what preschool should I go to, which nanny should I have. These are all important parenting decisions but I mean they’re rounding error compared to does your kid have genetics that are compatible with life or not.

13:45 Yeah. The other thing too is like even if you’re mostly like a functioning human in society, if you’re born with something that knocks you out for even months at a time or weeks at a time like celiac, if once a week you get exposed to gluten and that happens for the entirety of your life, that’s 52 days a year of slight under-productivity. That’s a huge amount of lost productivity for that human being.

14:14 And it’s crazy that you wouldn’t want to spend… I think I looked at it right before this, it was like $2,500 for one screening, right? Yeah. For each embryo. Yeah. How does that cost… Is that cost actually prohibitive in any way or what’s the main limiting factor right now to just scaling up massively?

14:35 I think it’s just knowledge honestly. I actually don’t think that the price point is really much of a problem because basically right now we’re still living in a world where a lot of people are paying out of pocket for IVF. IVF in the US costs around $30,000. In Europe it’s like $5,000 all in, including the medication. In the US just the medication alone costs between three and $5,000.

15:05 You know it’s a racket. We have worse laws in terms of affordability, bad incentives or something. Bad incentives around generics and things like that. So yeah, there’s this huge cost disparity just for IVF itself. And then also in a lot of European countries, IVF is covered. You don’t even have to pay that. So if you want to pay cash for IVF as an American, travel to Europe, you’ll pay $5,000 all in. But Europeans often it’s fully covered by their health insurance.

15:40 So there’s this massive difference in what the cost is in the US versus Europe and I think that also really drives utilization. If you make something free obviously a lot more people are going to use it than if it’s extremely expensive. So it’s kind of crazy that in the US we’re already living in this world where rich people get to have kids and poor people don’t because rich people can afford IVF and poor people can’t.

16:05 So the population of people who are already getting IVF today, where they either can pay out of pocket for it or they have coverage through their employer, for the vast majority of them $2,500 per embryo isn’t make or break. I think that the larger problem is how do we make it so that everyone can afford IVF.

16:25 So IVF now is taking that national stage. Trump is kind of famously saying that he’s now the father of IVF, which isn’t factually true, but it’s still great that he’s embracing the technology finally. So I think it’s great that it’s now getting that national attention and I think that IVF will eventually be covered. Next year it’s going to be covered in California and hopefully it’ll be covered nationwide.

16:55 And I think that’ll be a massive unlock because then all these families who are currently unable to afford it finally will. And then eventually I think that embryo screening will end up being covered as well because from the purely economic standpoint, what’s the most expensive outcome for young healthy adults? It’s a baby who’s in the NICU. And we just talked about how a quarter of those are genetic. So if you can avoid some of those most expensive, most catastrophic outcomes for your employee base, that’ll just net out positive for you.

17:30 Was there any things that you could have been born with, like genetic diseases that you just like got lucky on? Yeah I think there’s a lot. So basically, South Asians in general have really high rates of heart attacks and metabolic conditions like diabetes. So yeah, my grandfather got a double bypass. It’s just not fun. South Asians get heart attacks 10 years earlier and are twice as likely to die than almost any other ancestry.

18:00 So yeah, like that’s something that really matters to me. If you look at all cause mortality, what kills people most often? It’s cancer and heart disease. So heart disease is obviously up there. So yeah, that’s something that really matters to me in terms of okay hey with embryo screening you can cut your embryos’ relative risk by 30 to 80%. That’s a massive number especially since the base rate of heart disease is already so high in the population but then even higher, more enriched in South Asians.

18:35 So I think that’s a big one. Fortunately that hasn’t affected me yet but… Did you screen yourself for it and you’re good or not yet? Oh heart disease. Yeah, I’m actually fortunately not at super high risk. So yeah, I guess I got again kind of won the genetic lottery there too. But even what I’m saying is so even if you’re at lower risk, if you have a higher rate in your family, then you’re still at higher risk than average.

19:00 So I’m basically at average risk for South Asians, which is still higher risk than Caucasians. So basically, to me, that’s one of the most useful things to minimize risk for because the base rate is so high. Other families are super interested in things that are sometimes more rare like schizophrenia or bipolar disorder, but again, they’re kind of interested because they had a family member that was affected or they themselves have suffered from it.

19:30 So it really just depends. I think that’s something that is just pretty surprising to me because something that one person will think is totally inconsequential, doesn’t matter at all, is really important to someone else. Yeah, like I think celiac is one of those examples. Yeah, we got a really solid concoction in my family. I think one of my aunts has lupus which is also another fun one. But anyway, I’m very excited to basically screen out all that stuff from my offspring.

20:00 I think that’s awesome. I would be curious like personally I love… I would want to give my kids advantages and I’m wondering how soon are we going to be able to kind of screen for intelligence and that sort of thing. Yeah, I think people are primarily interested in health. I think there’s some interest in this type of stuff but the vast majority of families that we actually talk to, even if you just talk to people in general, they’re like oh how is mom doing, how’s baby doing, are they healthy and happy?

20:30 That’s the primary thing. There are models for some of these other things like height and eye color and hair color but Orchid focuses on health specifically because I think it’s just more important. It’s the most critical thing. But yeah, there are models for some of these other things. And I think eventually it’s probably going to become much less taboo than it is today to do that.

20:55 I mean, if you think about the history of IVF, sex screening was originally met with really intense backlash and a lot of moral hand-wringing. And now sex selection happens routinely all across the country. People do IVF cycles electively for sex selection. They call it family balancing. People will have two boys and they really want to have a girl for their third. So they come and do IVF totally electively. They don’t have any fertility issue and they do it for sex selection.

21:25 So it used to be that there was a lot of moral panic around that and now at least in the US it’s become much more standard. But at the same time even today if you think about India or China, sex selection is actually not allowed there. You cannot report the sex of an embryo in India or China. People in the US often have this impression that in China that’s the wild west and you can learn anything you want there but it’s actually much more restricted.

21:55 Surrogacy is also not allowed in China. So there’s actually a ton of fertility tourism from Asia and a lot of other parts of the world to the US to get access to advanced embryo screening like Orchid, to get access to surrogacy, or to basically just get uncensored access to information about their embryos and make these kinds of decisions.

22:20 I mean China famously had the one child policy. They also kind of engineered Yao Ming. They basically selected the tallest man and the tallest woman to get married and have kids together so that Yao Ming could be born. So they’re much less free than the US in terms of how constrained they are in terms of these pretty basic decisions about who should you marry, what information should you have access to during your pregnancy.

22:50 Is it more of a cultural thing or is it a religious thing or why do those specific countries not really embrace it in the same way that the US has? Oh, sex selection specifically. In China and India, there’s a very strong sex preference for males. So basically, if they were to reveal that information, then it would result in a really bad consequence. In the US, there’s just not as much cultural baggage around that. There’s actually a small sex preference toward women actually during IVF. So actually there’s slightly more female embryos that are chosen in the US.

23:20 So it’s kind of interesting. I think as a society, you have to know basically what’s the information hazard for parents in that society. And we kind of have to decide together what information should parents have access to and what information should they not have access to. Should be a little bit of a black box. Yeah. Exactly.

23:45 And I think India and China have made their own decision about hey sex actually would cause too many problems to give parents access to it and they’ve stuck with that I think for almost 15 or 20 years now. Is there any other information that’s not necessarily optimal to give to humans to let them decide or is it just mostly around sex?

24:05 Well I mean I think the other big question is all of these traits that you’re bringing up. So this idea of should parents have access to trait information like hair color and eye color and height and IQ. I think that is going to be a really big societal debate, like should parents in the US have access to it or not. It’s not just going to be a decision for Orchid to make specifically. I think it’s something that as a society we’re going to have to have a national conversation around what information should parents have and what is sort of too much information for parents to have.

24:40 So it’ll be interesting to see. I mean I think that Americans are pro-freedom and anti-censorship but you never know. There’s still people who are debating IVF today, still people who are debating birth control today, still people who are debating condoms today. So people have extremely different and strong opinions not just about what they themselves should do but what other people should be allowed to do. So there will kind of always be some people that are unhappy.

25:10 Yeah. Yeah. So it’ll be interesting to see how it shakes out. Yeah. What’s been the most meaningful experience that has happened through building this company?

25:25 Honestly, I think it happens quite frequently. It just means a ton to me anytime we receive a baby photo. Anytime that someone gets pregnant, they get to have a healthy, happy pregnancy. And they get to have a healthy baby. I feel like it’s the most meaningful thing that I could possibly do. It’s the happiest moment in their life and it gets to be a happy moment.

25:55 It’s really sad the other side of it, right? There’s so many people coming to us after they’ve had multiple miscarriages sometimes. They’ve had a late term termination. Sometimes you’re at 20 weeks, 30 weeks, late into your pregnancy and then you get an anatomy scan and you find a fatal anomaly. It’s horrific. A pregnancy is an extremely intense thing. You’re at your metabolic limit, you’re literally metabolically running a marathon every single day for 9 months to create this human inside of you.

26:30 And then the idea that midway through that process that’s so physically taxing, so emotionally taxing, you find out that this baby doesn’t have a skull, doesn’t have a skeleton, isn’t going to be able to come to term. It’s extremely traumatic. So being able to avoid that so that people are able to transfer embryos that are going to lead to a healthy pregnancy and are going to be healthy babies is… I couldn’t be more honored to be able to work at that moment in people’s lives because it’s something that has so much meaning for them and has such drastic consequences for that child’s future.

27:10 And on the flip side from the most meaningful thing, what is the thing that kind of keeps you up the most at night? I don’t know. I think that to me I’m really just worried about reaching more families. This idea that one of these catastrophic outcomes happens that didn’t have to makes me genuinely really sad. Because if people don’t want to do it then that’s totally fine. But if they just didn’t know that they could have done something and they would have done something differently if they had the information, that I think is really really sad.

27:45 And that’s why I think it’s really important to do these podcasts and constantly be talking about it and get as many of these families who’ve had a positive experience out there. Because it’s just something that I want it to be as standard as an engagement ring. Every time you talk about getting engaged, you think about this diamond. Okay, who really cares about this diamond? Doesn’t really matter. Versus the health of your baby is something that’s going to matter for their entire life.

28:15 There should be a conversation around how can we maximize the chance that this child is healthy. What are the conditions that run in our families that science understands a little bit better now that we can actually quantify and minimize the chance that something affects our child? I want that to be a more central part of the conversation around having babies. And I think that’s the thing that is the biggest worry: are there families that could benefit from this that just don’t know that it’s possible, that have never thought about this idea of I can make embryos, freeze them, and then transfer the one that’s unaffected.

28:55 I know I think I looked up earlier today and it was something like 2.5% of all births are IVF. Yeah. About in the US it’s about 2.5%. Do you know what the number is in Copenhagen? No. It’s almost 10%. Yeah. Is that crazy? It’s almost double digits and again it’s like… It’s subsidized by the government. It’s free for people.

29:20 So you get utilization that’s like… So is one of the things that you’re going to kind of have to do is try and figure out how to get the government support on rolling this out and making it basically free for people, just kind of incentivizing it?

29:35 I think that governments are going to choose to cover it. And I think that’ll trigger other governments to act. But the great thing about it is that it doesn’t require that to get started. Families around the country are already benefiting because they get to vote with their feet. They get to say that this is the thing that’s going to benefit my family and I’m going to go seek it out wherever it is that I have to go. Some people are taking flights from around the world to get access to this.

30:05 For a lot of Americans, it’s nearby in their city. They don’t have to travel too far to get access to it. And yeah, I think eventually it will be something that governments and insurance companies get involved in, but it’s kind of cool to be in this sort of little niche where… Little bubble of people that realize…

30:25 Yeah. Not even just the bubble that realized but it’s actually fortunate to be in this situation where a lot of innovation in healthcare actually gets killed because there’s not this alignment between who’s the person that benefits from it and who’s the person who’s actually paying for it. That distortion kills a lot of companies and kills a lot of great products and is kind of some of the reason why you have this sclerotic health care system that doesn’t actually help patients.

30:55 It’s because patients aren’t actually paying for it, the insurance company or the employer is paying for it. And that creates a lot of distortions. But what’s actually a benefit and a curse of IVF is that because people vote with their feet, because people are actually paying out of pocket, they can actually say okay I want Orchid, I want whole genome embryo screening, or I don’t. And if their doctor says no, they just go elsewhere.

31:25 And I think that’s actually really powerful to get people to change how they operate and upgrade to the latest technologies because the user is asking for it. Our users literally got us the vast majority of these IVF centers recruited. Patients literally came in and said that I’m not doing an IVF cycle with you unless I have access to Orchid.

31:50 How many times has this happened? I think we’re in over 100 IVF centers now. So like probably at least 70 or 80 times. The majority of the clinics and doctors that were onboarded were patient-led actually. Crazy. Which is really cool. Which is honestly insanely flattering that basically patients were like bulls in china shops and said that I am only going to go where I get access to Orchid, I want this data on my embryos.

32:20 So yeah, I think that’s hugely flattering and powerful. But that interaction doesn’t happen in the vast majority of healthcare. So it’s actually like… It sucks that so much of healthcare is stuck in the situation where because the patient isn’t paying for it, they don’t actually get to have a say in how to make things better for them. They can’t vote with their feet because someone else is voting for them kind of thing.

32:50 Exactly. Yeah. There’s someone in HR at their company who’s deciding what benefits should or should not be included in their health plan. And there’s someone at United Healthcare who’s denying access to this thing that they really want access to because of whatever bureaucratic process that they use to decide what should and shouldn’t be covered.

33:10 Yeah, I’m not surprised on the whole clinics deciding. I’m definitely surprised on 80. That’s crazy. I have not heard of customer-led sales for that sort of thing. That’s amazing. I do love there’s very few companies that have some form of what you have on your website, which is this wall of love. There’s an entire page dedicated to just love. How did you come up with that?

33:40 Oh, I mean, I just think that we just realized that the biggest way… The way the company started was me running my embryos. The first embryos that got run at Orchid’s Lab were me and my husband’s embryos. And then I basically went around with my embryo report to all my friends and I was like, “Hey guys, these are my embryos. Isn’t this so cool? I have the most data any human has ever had about my future babies before they’re even born. Isn’t this cool?” And they were like, “Yes, it is very cool. I actually want it for myself.”

34:15 And that’s actually how we got all of our first users. And that’s I think basically what led to the whole cascade after that. The strongest referral is from your friend. Think about how important of a decision this is. This is literally the most precious cells you will probably ever possess, your embryos. And then you’re going to send them to a random company to analyze them. You want your friend to have used it first.

34:45 If the person that you trust the most in the world says, “This worked for me.” Yeah. Exactly. And you met their baby and their baby’s doing good and doesn’t have whatever condition it is that they’re worried about. It’s a huge amount of trust. And I remember at the very beginning, I built the company because I wanted the product myself so I wanted to be the first customer for that reason. But I also don’t think I really would have been able to recommend it to anyone else honestly if I hadn’t done it myself.

35:15 Because I just think that’s how people are with their friends, right? If they haven’t tried something out and been like, “Hey, this is awesome,” they don’t want to recommend to their friends. So I wasn’t going to recommend it to my friends until I did it because what am I recommending?

35:35 Did it start out as a company or just as a curiosity of you doing it and searching it out yourself? No. It started out as a company. I started out doing a lot of different AI research at Stanford and then I kind of ended up stumbling into a genomics lab. A lab that’s basically joint… They have genetic data and they’re joint with the AI lab at Stanford.

36:00 And when I saw that, I kind of was really starstruck in the sense that when I was in elementary school and middle school, I remember hearing about the human genome project and eventually we’re going to have all this data and we’re going to be able to do all this really interesting stuff with it. But I was like, all right, well, I guess check back in 10 years.

36:25 And then 10 years later, I actually saw it. Now there was millions of people sequenced. You had their genetic data and you had their medical records and it’s true. You could build these models. And then for me, I was really interested in embryos at that exact moment because I was getting engaged and I was thinking about babies in the concrete, with a specific person rather than in the abstract.

36:55 And then having grown up seeing how your life can get totally derailed by a random genetic typo can result in going from a sighted person to a non-sighted person. It was sort of like, okay, the biggest parenting decision that I’m ever going to make is my child’s genome. So I want to be able to see everything at the earliest possible stage, before things start to go wrong, before you’re in this reaction mode of like, you’re in the room with the doctor and saying, “I’m so sorry, but there’s nothing else that we can do.” That’s the situation that you want to avoid.

37:30 So to me, I just saw it as if I’m going to do one thing for my kid, it should be this. And when you walked into the first IVF clinic to do this yourself, were people supportive of just like, hell yeah, go screen your genome, all that stuff, or what was that like?

37:50 Oh, well, I did it at Stanford and a lot of our medical advisors and stuff were from Stanford. So I’ve been working with them for years about it. So they knew that obviously I was going to want the maximum data. But I think there’s one of the things that I think is most interesting is just how much things have shifted in the last 5 years. I think we truly did create a category here.

38:15 There’s been a ton of copycats and people who have gotten into the space because of us. And I think that’s honestly really cool. Obviously mimicry is the highest form of flattery. So the fact that people are actually talking about reproductive technology, the fact that people are talking about artificial wombs, the fact that people are talking about IVG, in vitro gametogenesis, the idea of making egg cells from skin cells, I think all that is really exciting because it used to be way more sci-fi and now I feel like it’s become way more mainstream.

38:50 And this whole idea of embryo screening has also become way more mainstream. In the last six months alone it’s been in the New York Times, CNBC, GQ. Every major publication is talking about it and people are tweeting about it and these babies are getting not just national but international coverage. So I think that’s actually shocking to see how fast that shift from super sci-fi movie to you can go do it. And it doesn’t cost that much. And not only that, but it’s like their friends are doing it.

39:25 It’s now like I know someone who’s done it or I’ve met babies who are created this way. And I think that kind of familiarity really makes it much more concrete and tangible for people, but I think it also results in some of that outrage too because people are like, “Oh my god, it’s actually not just a movie now. It’s really happening.” And that feeling of this could actually be the default way that people have babies in the future. I think people are starting to see around the corner.

39:55 If you look at any new technology there’s first people that are like oh this is awesome. Then there’s some people that are like whoa this is… I don’t want that type of future, I don’t want to embrace it. But over time it generally trends towards people kind of forgetting about caring about it and then they all just kind of do the new thing. How has that been with IVF in the first place and then also with you now? Is it kind of mirroring what’s happened in the past?

40:25 Yeah. I think there’s always been these moral panics around every single reproductive technology. I think a lot of people don’t know that there was actually two different Supreme Court cases that were fought over condoms. Over women getting access to condoms. Yes, there’s two different Supreme Court cases. The first Supreme Court case was so that married women could get access to condoms and then the second Supreme Court case was so that unmarried women could get access to condoms.

40:55 Previously before those cases they were banned under obscenity laws. It was considered obscene for a woman to be able to control when she got pregnant. So the idea of doctors giving out condoms was literally something that people were jailed for. This is in the US less than 100 years ago. Is this like the 1950s we’re talking about? 1965 and 1972. Just for women to get access to condoms who are married and then till 72 to get access to condoms for unmarried women.

41:30 So it caused so much moral panic, so much consternation. It literally had to go to the Supreme Court to give women this right. So that’s just condoms. Then you think about IVF. IVF was met with pitchforks. There were calls for… There was insane moral panic around these test tube babies. And eventually these scientists won the Nobel Prize for inventing a technology where now millions of babies have been born.

42:00 The idea of the NICU itself, the neonatal intensive care unit where babies who are pre-term… The idea of spending money on that, there were a lot of doctors who were against that who said that there’s no way we can save these preterm babies, these dollars should be put elsewhere. Was this also like very recent in the last like 50 60 years? Yes. Yes. There was a lot of doctors saying that we should not actually invest in preemies, literally the smallest most vulnerable babies. We shouldn’t try to save them.

42:30 Insane. And epidural was met with a huge amount of moral concern. And it was basically this idea that women should feel pain during pregnancy because Eve fell from grace or they had different reasons for why. And then obviously there’s none of that when you’re in dentistry or when you’re getting… You should actually not use anesthesia when you’re getting your teeth cleaned or getting a cavity because we want to feel it for the love of the game. Yeah. Exactly.

43:05 So this idea of pain relief during pregnancy was also met with moral panic. C-sections were met with moral panic. I mean pretty much everything touching pregnancy, childbirth, babies… Even think about it, people will hate you if you breastfeed, hate you if you don’t breastfeed. Every decision surrounding pregnancy just ends up controversial, somehow ends up causing a holy war.

43:35 So it’s not really surprising to me that people are so activated about embryo screening too. But I think it’s just going to become something that’s as normal as birth control pretty soon. And I think that’s going to be exciting. But there’s going to be this transition period where people have to shake everything out. And I think that’s okay.

43:55 I mean, it’s not even just reproductive technology. There was a huge amount of moral panic around switching from candles to electricity. There was a huge amount of moral panic around people were genuinely afraid of elevator operators leaving. They were like, “Well, what if the elevator stops? What are we going to do? Are we going to trust these buttons or not?” And now obviously no one’s concerned about not having elevator operators.

44:20 But anytime there’s a big new technology, there’s a lot of concern about what is lost, what is gained, are we gaining more, are we losing more. We used to hunt all of our own food, now we go to the grocery store. Now we don’t have the same connection to meat as we used to when we were literally spending weeks hunting a single deer. Something was lost but also something was gained.

44:50 And I think that’s obviously going to be true for this as well. When you go to the grocery store, it’s this amazing selection of everything you could possibly want. Our ancestors would be shocked. They’re like I only get this once in my life and you have every single variety in all seasons flown in from all around the world. For like low low prices of an hour of your labor and you get basically whatever you want from the grocery store.

45:20 And then you could argue that okay this surplus created obesity or you’re not having seasonal food. Yes there are some downsides to the grocery store but I mean overall what do we want to do? Do we want to ditch grocery stores? We used to suffer from the cold or the heat, and then we developed air conditioning. Controversial for Europeans. And we developed houses. But we don’t say like, oh, God wanted us to freeze to death and not build a home for ourselves where we can be warm and safe in the winter.

45:55 So I think this is just yet another one of those things. How can we use science and medicine so that the most precious moment in your life actually gets to be a healthy and happy one? I don’t think there’s a better use of science and tech than here because the impact is so big.

46:15 When you started the company in the first place, did you kind of come into it with this understanding of past technological trends and the pushback that those received or was it one of those things where you kind of come in, you start offering, do it to yourself and then suggest it to your friends and all this stuff. And then you kind of over time start to hear people be mad. How…

46:40 I definitely experienced… I didn’t know about any of this actually before Orchid. Yeah. So, after Orchid, once I saw how activated people got, I sort of was like, “Huh, is this something we’re doing? Is this a standard thing?” And I got actually a lot more curious about it. There’s actually one Twitter account I really like. It’s called Pessimist Archive or something. Have you seen that one? Where they basically talk about all of the haters for every great technology.

47:10 They basically talk about all the people who didn’t want the moon mission to happen or didn’t want the human genome project or who thought the Golden Gate Bridge couldn’t get built. All the haters and it’s like pessimists don’t get stuff done. You kind of have to be an optimist to want something to succeed and it’s just like… But yeah, there’ll always be naysayers and sometimes there’s…

47:35 Was that difficult for your own experience starting the company and starting to have people react in that way? Was that difficult emotionally from just like… It actually really was. At the beginning it was actually extremely difficult emotionally because I thought… I think I lived in a small bubble of people at Stanford and San Francisco who were all just much more positive about it and I think I was just very ignorant to how much activation…

48:05 You assume that everyone else was also going to be as supportive. I don’t think that I assumed that, but I think I just… I didn’t… I always thought that like online… I was just a little bit naive. When people talked about online hate, I kind of dismissed it because I was sort of like, okay, if someone’s harassing you in real life, it’s something you can’t really avoid. Someone starts yelling at me, I can move, but I still have to experience their verbal attack.

48:35 Versus for online bullying, I was sort of like, well, but you’re reading the mean comments. Why wouldn’t you just stop reading them? It’s almost like you’re actively participating in bullying yourself. But anyway, once I actually kind of experienced it, I was like, “Oh, wow. Okay, this is a pretty weird… Humans have probably never experienced this amount of…” This is a new thing for the idea of a tribe of 200 people and if all 200 of them were mad at you, that was probably very bad. And so our brains really don’t like people being unhappy with us.

49:10 Yeah. So I think it was kind of surprising I think the first time. But I think this isn’t honestly unique to Orchid. I think anytime anyone does anything, not even significant, anytime anyone does anything on the internet, people seem to have lots of crazy opinions about it. Someone, Apple changes the font and people are super outraged.

49:35 So I think that if you’re going to get really dissuaded about what you do based on a random online mob, you’re not going to last long because the online mobs get mad about something significant or insignificant every single day. So I think when you put it in that context of oh well they also got mad about this font change or this color change… Wait 48 hours, 72 hours, it’ll be the next thing.

50:00 I think that kind of helps with perspective and I think the other thing is just from that historical perspective of don’t feel like oh this is just a you thing. This is just a standard thing that always happens to literally anything new.

50:15 For the very first IVF clinic that you guys signed on, that was just pure you going out and talking with them? Correct. The very first case was me. So yes, I talked to them about me. But yeah, after that all the additional cases were recruited by our patients. So I basically talked to a bunch of friends and then some fraction of those people did it and then they started recruiting IVF centers as they started doing it themselves.

50:45 Was that was that roughly or relatively easy once people started to go into IVF centers and say can you please use this and I want to screen everything? Was that a relatively easy sign on process or they pushed back?

51:00 There was pushback. Some people had to go to several IVF centers because people were like, “Hey, what is this new weird thing?” So I think it kind of depended. Some of the time people were more open to it. If they had a direct relationship with maybe one of our clinicians that we worked with who’s already used it, they’re kind of more open to it. There’s a lot of people who had to really be a bull in a china shop and run through walls and really pressure test their IVF center and their doctor into trying it out for them.

51:35 And then kind of the doctor flipped after that and they were like, “Oh, wow. These reports are actually really amazing and this is going to save me a bunch of time on this huge category of patients.” But that initial first step of just trying a new thing is really hard. So yeah I think we just ended up getting really lucky and fortunate that our first users were just incredibly persistent and demanding patients who wouldn’t take no for an answer and who said no I want this for my family and I want this for my baby.

52:05 So you’re right because basically if our first users happened to be more timid in some way then the whole thing might have never worked.

52:15 I would be curious, are healthcare companies disincentivized from having healthy people because if they have a bunch of rare diseases they can sell them drugs? Yeah. So the thing that’s really crazy is that in rare disease specifically there’s this huge incentive problem because each individual disease is too rare for a drug target to be profitable. So it doesn’t actually make sense to even spend the money on R&D to even attempt to find a treatment much less a cure.

52:45 So that’s something that I think is super sad. Gene therapies I think are really cool. There actually was a gene therapy called Luxturna, the first ever that was approved in the US for my mom’s condition. It cost over a million dollars per eye and it actually doesn’t even reverse the blindness. It just prevents it from progressing. So for someone like my mom who already had pretty advanced vision loss, it wasn’t worth spending $2 million.

53:15 And also, the Luxturna targeted one specific variant called RP65. There’s actually thousands of different variants that cause RP. So if you didn’t have that one specific variant, you weren’t even able to benefit from the gene therapy. So a tiny fraction of people were even able to benefit from an extremely expensive treatment that also again doesn’t reverse the vision loss.

53:45 So it’s actually we’re kind of living in the dark ages when it comes to medicine. And a lot of these drugs, they might have like a 30 or 35% relative risk reduction, but you only get that relative risk reduction if you’re perfectly adherent, meaning you’re taking the drug reliably every single day. There’s entire companies that are built around how do I convince people to actually take a drug every day.

54:10 So this is way more powerful than that. The idea that your child gets from just their genetics this benefit of being much lower risk for disease, even more so than what you would get from taking a drug, one of the best drugs. There’s drugs that make over a billion dollars a year that only have a 30 to 35% relative risk reduction. And you can get more than that with embryo selection from just five embryos.

54:40 No side effects because you already have multiple embryos and you had to choose one anyways. Before you were making that decision just based on a beauty contest morphology or just based on really limited literally just eyeballing it. Yes. I mean essentially… This one looks good. Click. Yeah, they call it morphology. They say there’s grading of embryos, but there’s also been studies that show that if you rotate those images, then the same embryologist will give a different grading for that embryo. So there is this issue with any sort of human visual grading system.

55:15 Crazy. But that was the best that we had at the time. And hey, it worked. It was better than nothing. It was some additional factor. But now there’s just so much more. It’s not just so much more information on the embryo, but it’s also geneticists have cataloged over the last 20 years what the cause of thousands of different diseases are.

55:40 Before, if you have all of this data, but you don’t know what to do with it, it’s not that useful. But we’re now at this moment in history where both things have happened. Now we can finally collect all this data off of the embryo which wasn’t possible before Orchid and then we now actually know what to do with it because geneticists have sequenced millions of people and we now know this is the molecular cause of so many different conditions. And then also for diseases where there’s not a single molecular cause we now know how to build models so that we can quantify risk for diseases that involve many thousands of different genes at once.

56:15 And I think that’s something that’s really cool because not smoking is a really great life decision, but it sucks that there’s this huge portion of risk that previously you’re just stuck with at birth. Literally rolled on lucky dice. Exactly. And that has sometimes… For a lot of the time it’s a dominating influence. Doesn’t matter how much you exercise. It doesn’t matter how healthy you eat. It’s a chronic thing that you can’t fix.

56:40 Exactly. And being able to even minimize that risk or take it entirely off the table is now something that’s a superpower that parents have. Let’s end it on what’s the hardest thing you’ve overcome?

56:55 I don’t know, man. The weather’s so good right now. I can’t think of anything negative. It’s a beautiful sunny day and you guys are just here. I’m like I can’t think of anything negative right now. I’m too positive of a person, dude. I feel like even if something bad happens then I’m like I don’t know, it’s like lifting weights. It’s like oh I got a muscle out of it. How is it bad? You’re more jacked, you’re a stronger person.

57:20 Jeff Bezos’s mom had this line where she said if Jeff’s unhappy wait five minutes. He just has this inability to be unhappy for any length of time. He just continually gets happy and then just grinds really hard.

57:40 Yeah. I don’t know. I’m not trying to be dismissive, but every hardship is an opportunity. Anything that’s really hard to do just ends up being a really good story later. So, it’s not really a hardship, right? It’s almost just like a cool story. There’s been lots of things that were hard building the company, but they were obviously good because in the end everyone involved, me and the great team that we’ve put together, everyone becomes more solid, more stoic, smarter because of it.

58:10 You have to get battle tested in order to build anything great so you got to… I feel like I’ve maybe learned or something just to have this attitude of excitement toward any problem. It’s like okay cool, we can solve it. It’s kind of part of the fun. If it was going to be super easy then…

58:28 It’s very strange. I’ve heard the saying like if I knew how hard it was going to be I wouldn’t have done it or something and I’m like I just don’t agree with that. Even if something’s extremely difficult, if it’s going to be super worthwhile and fulfilling to do, yeah I want to go do it. No, exactly. I hope I’m not too teenager about it or something but it’s almost like when someone says that you can’t do anything or something’s impossible, it gets you more excited. You’re like okay cool, if I prove them wrong then I’ve now… Some hero. It gives you a quest.