What If You Could Read the DNA of Your Future Child? | Noor Siddiqui | TED

For 300,000 years, every parent in human history handed their child a genetic hand they'd never seen. There was no way to know what was in it. No way to prepare and no way to choose health. The genetic lottery ran, and you got what you got. That era is over. And the way that we have babies is changing forever. But before we get into that, I want to start with you and how you got here. You began as two cells, an egg and a sperm, each carrying 23 chromosomes. When that egg and sperm met, sparks literally flew. A burst of zinc emerged to start your life. And this specific moment locked in your entire genetic destiny. Your mother produced two million eggs. Your father produced over 500 billion sperm. And the specific combination of egg and sperm that make up you is a one in a trillion chance. The odds of you existing at all are about the same as picking one specific grain of sand out of all the grains of sand on all the beaches on the entire planet.

You are wildly unlikely to exist at all. A different night, a different day, and it wouldn't have been you. Yet tucked inside that miracle for hundreds of millions of people is a genetic disease, waiting to take something from them. Their heart, their sight, their child. Something that will arrive regardless of how loved they are or how hard they fight. I grew up watching my mom go blind. It took years just to get the diagnosis, and after all the testing and all the office visits and all the uncertainty, the answer was, “There’s nothing we can do.” She lost her night vision first, then her peripheral vision, and then finally and slowly, her central vision too. It sucks to be powerless. It sucks to watch someone you love so much lose something so precious. And unfortunately, she's not alone. Four hundred million people around the world suffer from genetic disease.

That's more than the entire population of the United States. Half of those people that are affected are children. Ninety-five percent of those don't have an FDA-approved treatment. Scientists have now catalogued over 3,000 genetic diseases. You can’t pronounce most of them. You don’t know their names, but the people who are affected, who are living it day in and day out -- they wouldn't wish it on their worst enemies. I started Orchid because of my mom. I still can't accept the fact that she's not going to be able to see her grandkids' faces because of a random genetic typo in her DNA. I built this because I don't want my own kids to be stuck with their life getting hijacked by a random genetic typo. We were the first company in the world to be able to sequence the entire genome of an embryo created during IVF. A round of IVF creates anywhere from five to 15 embryos. And today, that incredibly critical decision is made either by a beauty contest -- what these embryos look like under a microscope -- or they're made with a tiny slice of genetic information that's actually available.

So this is what testing looks like today in the IVF office. They zoom in on a specific chromosome: Are both chromosomes present or not? If they're missing, it'll let you know. And if both are present, it'll tell you you're all good. And if there's an extra chromosome, 21, for example, that's called trisomy 21 or Down syndrome. But the way you need to think about this is that you have three billion bases in your genome, and it's organized like a book. So those three billion bases are in 23 different chapters. And all this chromosome testing is able to do is tell you if every chapter is present or not. It's not actually reading any of the letters in any of those chapters. So if in chapter seven or chromosome seven, there's a typo, there's a spelling error, it's not going to be able to find it. It's just going to tell you, hey, you know, "Chapter seven is all good. I only checked at the chapter level." So that's where whole genome sequencing becomes incredibly valuable because it’s actually reading every single letter -- all three billion of them.

So what does that actually look like? So if you zoom in to a specific chromosome, you're going to see a bunch of letters. And hidden in those three billion letters is a typo. And unfortunately, just a few letters can be the difference between a child that will never be able to talk and one that will. That’s all that it takes: is a few letters changed. The reason that it's really hard to do this, and we're the first to do it in the world, is because embryos have extremely small quantities of DNA. The embryologist only sends us five cells, and in those five cells there [are] 30 picograms of DNA. A picogram is a trillionth of a gram. So we're working with extremely tiny amounts of material. And we had to invent an entirely new technology to amplify or copy that DNA hundreds of thousands of times without corrupting it. Now we know that it works because we have embryos, and we have the subsequent babies that were born nine months later, and we've matched them up and we know that they match.

So, cool technology. What does it actually let parents do? So what's really exciting is that at the most basic level, what we're able to do is allow parents to understand and screen for those 3,000 diseases that we talked about. Birth defects, heart defects, skeletal defects, neurodevelopmental disorders, genetic forms of autism, all genetic diseases that are completely missed by existing testing. But we can go even further than that. Think about schizophrenia or bipolar disorder or heart disease. These are diseases that are driven by the cumulative impact of many millions of variants working together. Some people are at high genetic predisposition and other people aren't. So what's amazing and what's available now is that now we have data from hundreds of thousands of individuals. We have their sequenced data, and we have their medical records so we can build models that quantify disease risk at the embryo level. So we can tell parents, this embryo is at a high genetic predisposition, and this embryo is at a low genetic predisposition.

And despite the fact that these models have millions of variants inside them, someone who's going through an IVF cycle who has only five embryos can expect to see anywhere from a 30 to 50 percent risk reduction with just those five embryos. And today, the models are the worst they're ever going to perform because we have the least data that we're ever going to have. Every year, we're getting more and more data, and these models are getting more and more powerful, which is going to translate to parents being able to reduce more risk with fewer embryos. And the best part is this isn’t sci-fi. These babies are actually already here. They’re being photographed by “The New York Times,” and they're making international news because their parents have done something that has never been possible before. We are the first generation, the first life form, to be able to read its own source code and actually choose the next generation. We are the first to get to choose health, not just have to hope for it. Soon this is going to be the default way we all have babies.

And here's the thing most people don't realize yet: sex is for fun, and embryo screening is for babies. (Laughter) Those two things have quietly separated. And once you see it that way, the question [isn’t], Why would anyone do IVF electively? The question is, why would you do it any other way? I want you to meet someone. This is Mia. Mia was born with lissencephaly, a terminal brain disorder. Most children with her condition don't make it to their 10th birthday. There was a genetic mutation, no cure and no warning. Mia's mom did all the genetic testing that you've heard of: carrier screening, NIPT. And because those tests only evaluate less than one percent of the genome, they're not able to identify the vast majority of these genetic diseases that we're talking about. So there was no way for her to know. She used Orchid to screen her next embryos. She's pregnant now. And despite living with the tragedy of Mia's diagnosis, she's able to go into this next pregnancy more confident and with a little bit more security that her next child isn't going to have to suffer in the same way that Mia does.

Same mother, same love, different outcome. Not because of luck. Because of a choice. It can be hard to understand just how powerful a single base pair can be. Think about the tallest woman on Earth -- she’s over seven feet tall -- and the shortest woman on Earth, she’s just over two feet tall. The tallest woman has a condition called Weaver syndrome, and the shortest woman has a condition called achondroplasia. Both of these diseases are actually caused by one letter changed in three billion letters. And I think that's miraculous, that one letter can have such a dramatic difference. They're also both spontaneous mutations. So what that means is that there's no one else in their family that has these typos. They're the first ones to have them. You know, women get a lot of flak for their eggs aging, but something that men usually don't know is that sperm actually accumulates mutations as men age as well. And there's actually a whole category of genetic diseases that are just caused by mutations in sperm that don't affect men.

And one of them is achondroplasia, one of the most common causes of dwarfism. So the genetic lottery doesn't only deal risk. It also deals some superpowers. This is a Finnish Olympic skier. He has a single base-pair change in a gene that controls red blood cell production. So that means that his muscles get way more oxygen than his competitors'. He has way more endurance and was practically unbeatable during his reign. There's a family in the Midwest that has eight times the bone density of anyone else that has been documented, and their bones are virtually unbreakable. You and I have only three color receptors, but there have been women found to have four color receptors. So while you and I can only see a million colors, they can see 100 million. They're living in a world that we literally can't picture. Extra endurance, unbreakable bones, 100 million colors. These aren't science fiction. They're already here. They're just currently given out by a genetic lottery.

And I know what some of you are thinking: playing God, unnatural. But I actually think the exact opposite is true. I can't think of anything that's more natural and more human than wanting to protect your child and wanting them to suffer less. We've just never had the information before and now we do. I want to show you one last family. This is Lydia -- Rohan and Jen’s first child. She was born with a very serious neurodevelopmental disorder caused by a single-base-pair-mutation in a gene called KCNQ2. This is what the first few weeks of her life looked like. They wanted a sister for Lydia, and they used Orchid for their next pregnancy. This is Lydia’s newly minted younger sister, Lucy. Same parents, same love, different outcome. Not because of luck. Because of a choice. Lucy won't become a patient before she becomes a person. She just gets to be a kid -- and because of what her parents did before she was born, she will.

The future is not hypothetical. It is being born right now. This is the first generation who gets the genetic odds stacked in their favor. Thank you. (Applause) Sal Khan: I'm going to put two questions into one that I'm guessing many people are asking. One, this isn't free. So you mention the genetic lottery, but does that stack the deck for those who have the ability for the resources? And then where do you draw the line? You kind of hinted in the end of superhuman sight or bones or endurance. Where would you draw that line with CRISPR and everything else? Noor Siddiqui: I think that in terms of cost, you know, in contrast to what these diseases cost, it's actually, you know, pennies on the dollar, right? So the genetic condition that my mom has, retinitis pigmentosa, the first gene therapy that was approved costs a million dollars per eye. So in comparison, IVF embryo screening is quite affordable. But yeah, in terms of where it goes, that's kind of why I'm here at TED.

It’s really up to you guys: Where do you want to see it go? I think that's going to be a really big societal conversation that needs to be had, because the technology is moving so quickly and the capabilities are moving so quickly. SK: A lot of food for thought. Thank you so much, Noor, that was awesome. (Applause)