What if you could read the DNA of your future child? | Noor Siddiqui

Host Elise Hu introduces Noor Siddiqui’s central claim: for roughly 300,000 years, parents had no way to see or prepare for the genetic traits their children would inherit at conception. Siddiqui describes conception as an extraordinary combination of an egg and sperm. An egg begins with one of roughly 2 million eggs produced by the mother, while the father produces more than 500 billion sperm; the particular combination that creates one person is described as a one-in-a-trillion event. Siddiqui compares the odds of existing to picking one specific grain of sand from all the beaches on Earth. She then contrasts that improbability with the genetic diseases that can be hidden inside it. Siddiqui says 400 million people worldwide live with genetic disease, about half of them children, and that 95 percent of affected people do not have an FDA-approved treatment. Scientists have cataloged more than 3,000 genetic diseases. Her motivation is personal: she watched her mother lose night vision, then peripheral vision, and eventually central vision because of retinitis pigmentosa. Years of testing produced a diagnosis but no available action. Siddiqui says she founded Orchid because she cannot accept that her mother may never see her grandchildren and does not want her own children’s lives hijacked by a random genetic “typo.”

Siddiqui says Orchid is the first company able to sequence an entire genome from an embryo created through IVF. A typical IVF round produces five to 15 embryos, and the decision about which embryo to implant is traditionally based either on appearance under a microscope or on limited chromosome testing. That testing can determine whether whole chromosome “chapters” are present, missing or duplicated—for example, an extra chromosome 21 indicates trisomy 21, or Down syndrome—but it does not read the individual DNA letters within those chapters. A human genome contains about 3 billion bases arranged across 23 chromosomes. A disease-causing change may be only a few letters in a chromosome, so standard chromosome screening could declare a chapter intact while missing a critical spelling error inside it. Orchid receives only five embryonic cells, containing about 30 picograms of DNA—one picogram is a trillionth of a gram—and had to develop a way to copy that material hundreds or thousands of times without introducing errors. Siddiqui says the company validated the method by comparing embryo sequences with the sequences of babies born nine months later and finding that they matched.

At its most basic level, Siddiqui says whole-genome screening can identify risks for the roughly 3,000 genetic diseases that existing testing can miss, including birth defects, heart defects, skeletal defects, neurodevelopmental disorders and genetic forms of autism. She also describes a second capability: estimating predisposition to conditions influenced by many variants acting together, such as schizophrenia, bipolar disorder and heart disease. Because researchers now have sequence data and medical records from hundreds of thousands of people, they can build models that estimate an embryo’s relative genetic risk. Parents might be told that one embryo has a higher predisposition and another a lower one. Siddiqui says that, even with only five embryos in an IVF cycle, families can expect a 30–50 percent risk reduction using the current models. She acknowledges that the models are currently at their weakest because the available dataset is smallest now; as more data are collected, she expects the models to improve and allow greater risk reduction with fewer embryos. She emphasizes that this is not speculative: children selected through this process already exist and have been covered by the New York Times and international media.

Siddiqui frames the technology as a historical shift: humans are the first life form able to read their own “source code” and choose aspects of the next generation. She says people can now “choose health” rather than merely hope for it. Her provocative formulation is that “sex is for fun, and embryo screening is for babies”: once reproduction and embryo selection are understood as separate activities, she says the question may shift from why someone would electively use IVF to why they would not. She illustrates the potential with Mia, a child born with “less encephaly,” a terminal brain disorder that usually prevents children from reaching age 10. Mia’s mother had undergone carrier screening and noninvasive prenatal testing, but those tests examined less than 1 percent of the genome and did not identify the mutation. After using Orchid to screen her next embryos, the mother is pregnant again and has more confidence that the next child will not face the same condition. Siddiqui summarizes the contrast as “same mother, same love, different outcome”—not because of luck, but because of a choice.

To show how consequential tiny DNA changes can be, Siddiqui compares the tallest and shortest women in the world. She says the taller woman has Weaver’s syndrome and the shorter woman has achondroplasia, and that each condition results from a single changed letter among 3 billion. Both are spontaneous mutations rather than traits inherited from another family member. She also notes that sperm accumulate mutations as men age, including mutations that do not affect the men themselves; achondroplasia is one example. Siddiqui says the genetic lottery can produce advantages as well as disease. A Finnish Olympic skier had a single base-pair change in a gene controlling red blood cell production, giving his muscles more oxygen and exceptional endurance. A Midwestern family has been documented with eight times the usual bone density and nearly unbreakable bones. Some women have four color receptors rather than the usual three, allowing them to see as many as 100 million colors instead of about 1 million. These traits already exist, Siddiqui says, but are distributed randomly. In response to concerns about “playing God” or being unnatural, she argues that wanting to protect children and reduce their suffering is itself deeply natural and human.

Siddiqui’s final example is Lydia, the first child of Rohan and Jen. Lydia was born with a serious neurodevelopmental disorder caused by a single base-pair mutation in the KCNQ2 gene. Her parents wanted another child and used Orchid during the next pregnancy. Their younger daughter, Lucy, did not inherit the disorder. Siddiqui again describes the result as “same parents, same love, different outcome,” emphasizing that Lucy will not have to become a patient before she gets to be a child. She concludes that the future is already being born and that this is the first generation whose genetic odds can be deliberately stacked in its favor. In the brief Q&A, TED’s vision steward Sal Khan asks whether the technology will favor people with financial resources and where the line should be drawn, particularly regarding traits such as enhanced sight, bones or endurance and future tools such as CRISPR. Siddiqui replies that, compared with the cost of treating genetic disease, IVF and embryo screening are “pennies on the dollar.” She cites the first approved gene therapy for her mother’s condition as costing $1 billion per eye. On limits, however, she does not offer a firm boundary. She says the question requires a major societal conversation because the technology and its capabilities are advancing rapidly, and tells the audience that deciding where it should go is ultimately up to society.