Orchid founder Noor Siddiqui on whole-genome embryo screening: giving IVF parents 100x more genetic data

it's so low that the benefit of being able to catch I never knew that. You're like I never would have done this. You're like, I'm hearing this for the first time. Anyway, we have Noradiki in the studio. Welcome to the stream. How you doing? What's going on? Welcome to the show. Oh. Uh, one second.

We're we're we're we're redesigning the studio. Can you give us another introduction? Hey, thanks so much for having me, guys. Great to see you. Thank you. Uh, good to see you now. Um, we're we're assembling the plane as we're flying it. Uh, anyway, uh, thanks so much for joining us.

Uh, take us through the last 48 hours. Last 48 hours. And also just like there's this weird thing that happens when like clips get sent out into the internet out of context. Like how did you feel the interview with Ross Douet of the New York Times actually went? Um because obviously it was a much longer conversation.

Uh this particular moment seems like heated. Uh but what was the actual uh what was the actual uh interaction like? And then what have the last 48 hours been like? Yeah. Yeah. Um no, I think the interview was really fun.

Honestly, I think that uh it was um yeah, just just really cool to be able to um chat with someone who has, you know, such a different perspective about the technology. But um yeah, it might help to just kind of back up and just kind of explain, you know, what Orchid is.

So um what Orchid is is we allow parents to protect their children from conditions um before pregnancy even begins. So kind of, you know, to set the stage of, you know, what happens now, um when you do IVF, you're basically operating blind, right? So you have extremely limited information.

Um a tiny percentage, one percentage of the genome is what's usually evaluated in order to make a decision about which embryo to transfer. So what Orchid does is you we're the first company in the world to be able to allow you to screen the entire genome. So 99% 100x the data compared to what what existed before.

And what that allows you to do is it allows you to detect conditions like birth defects, heart defects, pediatric cancers, some of those super severe disorders that previously you wouldn't find out until after the child was born.

So the exact same testing that happens um you know in the NICU after a child is born um you know those diseases instead of having to wait until you can only react when you you sort of have a conversation with a doctor and all they're able to tell you is hey there's nothing you can do.

that information is brought all the way up to that embryo selection stage to be able to actually transfer an embryo that's unaffected.

And I think the thing that's sort of really interesting about what's going on in this debate is it seems like people kind of don't understand or don't or maybe just ignorant of what's going on, right?

Because this whole question of, you know, should embryos be created and should people have the right to decide which embryo to select has has already been happening, right? IVF has already been going on for 40 years and for the last 30 years they've had access to really limited information. Right?

So all Orchid is doing is basically upgrading that information from hey do you want to get 1% do you want to only know that chapter level chromosome level um to do you want to know you know the entire book the entire genome and be able to scan for the thousands of different genetic diseases that geneticists have cataloged over the last decade.

So that's the thing that I've actually found really surprising is that there's a lot of activation about this topic, but maybe there's sort of a little bit of ignorance about, you know, what's actually going on here, right? Like there's no net new embryos that are being created.

It's sort of like you have this many embryos that are created during IVF. That's just how IVF works. And you have a choice. Do you want to make that information?

Do you want to make that decision with, you know, blind or with very, you know, limited information or do you want to make that decision with the maximum amount of uh information that science can give you?

Yeah, I' I've heard it's actually not technically blind that uh during IVF doctors will often just look at the embryos like v visually with their under a microscope and just kind of be like that one looks good and they'll they'll grade them like a b c d and it's extremely like vibes based.

They do actually look at them and grade them. Correct. Yeah. Yeah. It's a It's kind of a beauty contest. It's called morphology, but um it's a little bit tricky because, you know, they've done a lot of studies where there's, you know, if you basically flip the images, then an embryologist might grade them differently.

So, yeah, morphology is useful, but it's not, you know, kind of necessarily the most reliable. And I think the other piece of the debate that I think is really missing is that, you know, you kind of mentioned um, you know, testing that happens during pregnancy, right?

So again when you test during pregnancy at you know maybe 10 weeks um the amount of information that you have there is again super super limited right so you might be able to screen for something like down syndrome down syndrome is called is you know techn the technical term for it is tricome 21 you have three pairs of chromosome 21 it's actually not a lethal condition right it's survivable and right now all across the country in the US and all across the world you can get that information at 10 weeks right and right now women are in this um you know at this point where you the only option that they have is either to terminate that pregnancy or to have an affected child, right?

So, if you're in that camp that is against abortion, then you should actually support orchid and embryo screening because it obiates the need for that termination to ever happen, right? Because you only transfer the embryo that's unaffected.

Um so that's the other piece of it that I thought was really surprising is that you know maybe people don't realize that you know genetic testing on a very limited basis is already happening and terminations are already happening on the basis of you know non-lethal conditions right versus what orchids doing is is is looking at situations that are much more severe than that right so um you know over 20% of infants die due to genetic causes right if you look at babies that are in the NICU that unfortunately don't make it they've sequenced them and they found that at least 20% of infant deaths are due to genetic disease.

Right? So, I think it's insane to tell parents who are doing IVF that they shouldn't scan for, you know, lethal disorders when, you know, we're already doing um, you know, elective terminations for totally non-medical reasons, right?

Just because people, you know, don't want to have a pregnancy at a specific time or for, you know, a specific medical reason, right? Much much later than, you know, an embryo that that's five days old.

So, I don't I think that's something that I found kind of interesting is that um back to like Ross's like like Ross's like core point uh I the way I took it was like like it's pretty easy to make like a utilitarian argument that that this is a net good and this trend not even orchid specifically but like this this general trend of IVF is is a net good because it results in like less suffering.

Um, but his point was that there is a downside and and uh and I'm wondering if you debate that point or if you or if you say yes there is a downside.

We are losing something that poets write about but it's worth it because there I could make this argument about basically everything like space travel it's going to like SpaceX is going to wind up killing Earth. Another way to look at it is like if the water used in data centers I'm okay.

I think that's a good use of water. There's a million reasons why where I'm okay with trade-offs. Yeah. I mean, I think if somebody just watched that short clip and and clip was so brutal to fullness of the interview. They they might not pick up that.

I think it'd be insane if somebody's doing IVF and they're not using orchid, right?

Because if you're already going through this process and then you're saying, "Well, I don't Yeah, I'll just I'll just let the doctor kind of like do a vibes-based analysis of the embryos and he he'll just pick um you know, a beauty contest as you described it.

uh the you know seems like an obvious decision if you're going through that process to to leverage the max amount of data that you can have. Totally. But then I think a lot of people were being triggered about this broader idea of like what what would we lose if if every if every baby Yeah. Yeah.

That's Ross's question is like is like if there's a future where where being able to do more genetic testing pushes more people towards IVF, do we lose something? Do you do you agree with that? Do you debate with that? Do you think that uh it's worth it? Yeah. Yeah. Yeah.

I think it's sort of uh basically fundamentally a you know personal decision like a private decision, right? I think for each individual couple, each individual person, you know, they'll decide, right? Do I lose more or do I gain more from that decision?

That's why I thought I think I was kind of surprised that he was asking me sort of like, hey, it's it's not really my decision, right? Each parent is going to decide if they're losing more or gaining more.

And I think that yeah, if you think about any technology, right, like when we swapped um, you know, candles for electricity, when we swapped horses for cars, right? Um, you know, there's always something lost, right? The question isn't, you know, is something lost? Every with every technology, something is lost.

The question is, you know, what's gained, right? So, you know, when you have the decision of you, do I want to use an epidural during my pregnancy? Is something lost?

I mean certainly some women who choose not to use epidural because you know they think that you know what they gain from you know natural child birth is better but it's just it's just fundamentally a personal decision and it seems strange to um you know dictate to people or stigmatize people who choose you know epidural or not or you know to to screw their embryos or not.

Yeah. it kind of like uh I mean that plays out to all of technology.

like we recently found out that the the Amish population is doubling every 20 years and that uh by the year 2030 uh uh 2300 there will be more than 7 billion Amish people and so like even though the people I mean people people can make a choice they they can choose not to choose not to use IVL choose not to use anything there's a potential future where where groups like the Amish continue to just operate without technology and then there's a large amount of people that decide I it's worth it for me to go through this process and leverage technology to avoid a child with a a a permanent heart defect or or something of that sort.

But I think that's a scary Yeah, that's a scary it's it's a scary world I think for a lot of people to imagine. Uh which one's the scary world? Uh, I think a lot of people that have I mean, it's easy for parents that have gone and and had a healthy child through the natural process. Yep.

To think about a scenario where nobody humanity no longer experiences that at scale. And then you you the the other side of that is parents that have had a child with uh some type of of um compromised health to some degree.

uh that that would probably in some cases do anything to go back and and avoid having a child that you know died shortly after childirth or didn't make it through the full or or the opposite.

I mean there I'm sure if you talk to parents who have had health complications and gotten through it in many ways they would say they wouldn't trade that for the world like like they they see that as like something that was a crucible that they needed to cross and that was something that even though it feels very bad they they feel like it made them stronger in the long term but yeah I don't know it is tough it's a very hard situation what yeah sorry go continue oh yeah I mean I just think that it's just a super private decision, right?

I just think it it seems super strange for people to be um you know trying to push their ideology on other people.

I think it's just like, you know, we there's so much um in the way right now of, you know, people having babies and fundamentally one of the biggest anxieties people have is, you know, is the disease that I'm affected by, is the disease that, you know, um affected my my sibling or my parent going to affect my child?

That's sort of like front and center, I think, for a lot of people is, you know, most basic moral um desire I think people have is, you know, I want my child to suffer less than me, right?

So any tool that's uh available I think should be you know just um you know should be available to parents so that they can make that decision for what's right for their family and you know if they think you know more is lost by you know not doing it the old fashioned way then that's what they should do and no one should um you know stigmatize that but I think you know the same is true in the opposite direction and I think that unfortunately there's um yeah there's still like a huge amount of of stigma around uh IVF and embryo screening that I think shouldn't exist because it's such a massive force for good, right?

Like there's sort of this huge category um you know of illnesses that previously we just had absolutely no control over. We just had to roll the dice, right? And I think for a lot of parents, they're thinking that hey, this is going to be the most important parenting decision that they'll ever make.

I mean, that's, you know, fundamentally what what I think, right? I mean, there's no parenting decision that I'm going to make that I think is going to be as significant as is my child going to be affected by pediatric cancer? Are they going to be affected by developmental delay? Right?

If you look at children today um you know 60% of kids with moderate to severe intellectual disability there's a definitive molecular cause there's a genetic cause for that right and a lot of those are denovo mutations that means they happen spontaneously in the embryos so that so that means that even if you scan the parents ahead of time you you don't you can't mitigate that risk so um you have to screen the embryos you have to look at the earliest possible stage and I think that it's more compassionate to do that than to put women in this position where you know they're already pregnant and then now they have to make this decision you know during pregnancy as opposed to let me actually have a pregnancy that's successful right so 50% of miscarriages actually are you know due to genetic causes as well so it's like you know as a woman you're going through sort of the most intense physical experience right a pregnancy is like a marathon every single day um it would be it would be nice if you know you didn't have to have as many miscarriages right so what very obvious like it's just information that people should should have access to.

Yeah. What's actually going on on the science side? I feel like we sequenced the genome like 20 years ago. People were getting genome sequenced in the mail like 15 years ago. Uh but just now we're able to sequence embryos before they get implanted for IVF.

Like has there been some sort of fundamental scientific advancement? Is it a cost thing? Like did the FDA approve something? Like why is this now instead of like 15 years ago. Yeah. Yeah. Yeah. There's a couple of things. So, one, um, you know, specifically in embryo, there's a really tiny number of cells, right?

So, you have about 125 cells on day five and then five cells get sent to orchid for analysis and in those five cells, you only have about 30 pigs of DNA. So, you have a really, really tiny amount of DNA. Got it? And you have to amplify that DNA.

So, Orchid had to invent a new protocol, a new amplification technology in order to get really high quality whole genome data off of embryos. Um, so when you have blood or saliva, you can get a whole genome sequence through a commodity process because you don't have to amplify it.

You have enough DNA to just throw it on a sequencer. So, that's one piece of the puzzle.

And that's like the shotgun sequencing that uh 23 andme does where they're where they're just kind of like taking the average DNA that they're seeing in a bunch of different saliva and they have so much volume that they can like piece it together. Yeah. So, so, so basically 23 and me is a saliva based test, right?

So, when you have saliva or blood, so where's the DNA? The DNA is in the nucleus, right? So, if you have saliva or blood, you have a ton of cells, right? Yeah. Millions of cells. So, you don't have to amplify the DNA, right? You just have enough DNA in the in the blood to just do it straight up.

And the other thing is that 23 and does not do whole genome. They do something called an array. So, an array is just a subset of the whole genome. So, instead of looking at three billion letters, you're looking at like maybe 500,000 letters. So it's again that sort of less far less than 1% number.

So if you look at a tiny fraction of the whole genome, you just can't scan for all the diseases. So basically one piece of it is just can you read the data off of the off of an embryo, right? So orchid the first to be able to do that. And the second is what can you actually tell when you have the whole genome.

So that's um you know sort of the collective genetics and scientific community has worked on that over the last two decades to be able to catalog these thousands of different genetic diseases. Right? We didn't used to know what is the genetic basis of um you know lots of different heart defects.

We didn't know before the genetic basis of of u you know syndroic forms of you know some of the most severe forms of autism right we had to actually catalog that by sequencing you know millions of people over the last decade or two.

So part of that is okay you know it's the first time you can actually read the data at that super early embryo stage and the second is okay what is the actual things that are going to be clinically meaningful to parents uh during that stage.

So and and then sort of the third part of that is you know what models can you use to be able to um predict and quantify risk for not the just those binary yes or no is that embryo affected or unaffected by a specific genetic disease but can you actually quantify genetic susceptibility for conditions where it's not just a binary yes or no that's kind of like the polygenic side of it.

So there sort of three different things that are kind of coming together to make um embryo screening. Yeah. So the science kind of advanced. Um what what what's going on in the FDA side? Have you do you have approval? Do you need approval?

Like uh can you is it a different pathway than kind of the traditional uh like pharma drug pathway that we're familiar with from you know cancer drugs phase one phase two phase three. The way that the way the FDA uh regulates all testing not just embryo testing is through something called LDTS.

So laboratory developed tests. Sure. So um yeah there's basically two different agencies. One is called CLEA, one is called CAP.

They operate at the federal and state level and they come and you know inspect our lab and make sure that um you know uh you know all the machines work and all of the you know all the analysis that we're doing is correct.

So sort of these independent um audits that happen at the um yeah basically at the state and federal level annually. Interesting.

So it's more like an ongoing process than like you get approved and then you have a patent and then 10 years later there's like a copycat knockoff product that's like the the the generic version. It's a very different pathway. Uh well, so sort of I guess there's a couple of different things, right?

the the patent on the amplification technology is sort of separate from the separate FDA.

But the regulatory environment is that laboratory developed tests are regulated via LDTS which means CLA and CAP these two different agencies actually come and examine labs at the at a physical level and at an analytical level right they come and you know verify that um there's something called like proficiency testing right so they basically send you DNA sequences and they test you and they say hey did you you know call this correctly or incorrectly right so they sort of uh you know blind you to the results and that's kind of the the process for actually validating genetic tests right so orchid is genetic test on embryos and a sort of larger framework which is how do you validate genetic testing on you know blood or saliv?

No, I think I think uh it's such a I think it's like such a personal technology.

It's like a like the most businesses do not have uh you know as they're growing and marketing their product service technology they're not there there's I think few things few products on on earth that would be potentially more controversial where one person might see Orchid and be massively relieved and uh you know immediately reach out and and want to learn more and then another would probably send you a very nasty DM.

Uh but uh but I think it's um so yeah, I think, you know, it's it's not even I don't even feel like somebody that traditionally comments on business, you know, having having had two kids going through, you know, that that process as a family.

I think there's so many decisions along the way that are just deeply personal that should be made within the family unit. And I think, you know, whether somebody uh decides to use something like this or not should be again like everyone should just make their own.

You shouldn't listen to a podcast to get two, three, four kids the old way. Have two, three, four kids with Orchid. See how each plays out. Then you can judge the company. AB test. Just AB test it. Or or run a run a Gatka experiment. Have one the oldfashioned way. Have one superhuman.

And then see who can swim the farthest. I know you haven't seen Gatka. It's a great movie. Anyway, thank you so much for stopping by, Nor. Yeah, thanks for having me guys. Have a good night. Cheers. Bye. Bye. Um, you you really haven't seen Gatka? That's so insane. Have you seen Gatka, Tyler?