Saving Lydia: Why I’m Open Sourcing My Baby To Save Her and Millions of Others
Jen and I both grew up in different countries, studied Computer Science, moved to San Francisco and made it our home. Six months ago, we had our first child, Lydia. Lydia has a random genetic mutation that will leave her severely mentally and physically disabled. She will not sit up, crawl, walk or talk. Some kids have died. We were told her disease was too rare, and there was no treatment, but neither is true. There are millions of children with severe mutations like Lydia’s — and the technology to silence these mutations already exists.
Lydia Niru Seth
Lydia was born on her due date with the chubbiest little cheeks. We named her after her grandmother, Niru, who passed away exactly a year before. Her grandmother was full of joy and laughter, and that’s what Lydia represented to us. But, our joy was short lived — Lydia started having seizures soon after birth. She spent the next 3 weeks in the NICU fighting for her life and undergoing countless tests. Finally, we got a genetic test result. A tiny random mutation in a critical gene that will affect her brain function, causing severe disabilities and suffering.
As any parent facing this devastating diagnosis, we set out to do anything we could. Over the past six months, we have read hundreds of scientific papers, established relationships with world-class scientists, translated medical records from a foreign country, self-compounded a drug at home and raised over $1.5 million to form a non-profit to fund research. We now know that Lydia still has a chance. We can treat her in months. The traditional pharma model isn’t set up to help Lydia and millions of others like her. Here’s why…
The Problem — The Long Tail
There are six billion characters in our DNA. All of us have spontaneous typos in this code — a mutation. Some typos, like Lydia’s, cause serious diseases. Collectively, there are seven million people in the U.S. suffering from typos that affect the brain. Majority of affected are children. This doesn’t include the millions who have already died from these. Pre-natal genetic testing does not look for these. Because a typo can happen in one of billions of characters, there are only a handful of patients with the exact same one. For Lydia’s, there are only two others in the entire world — one in Greece and one in England. At position 683 of the gene KCNQ2, an A was mistyped as a G. That’s all it took.
This is a classic long tail problem — no mutation is common enough, but collectively there are tons. The existing Pharma approach to treat these is broken — they look for common typos and fix them with long drawn out trials. This barely makes a dent. Worse, they have put each in its own bucket and labeled them as rare, so the majority of the world feels they‘re not important to fix. How can these be rare when collectively there are millions with these mutations? The rare label is wrong and limits progress. These are not rare. These are genetic and have the same root cause. We need a systematic, platform-driven approach to fix these typos. We need a spell check.
The Solution — An N-of-1 Platform
Monogenetic diseases are unique from the vast majority of cancers and cardiovascular diseases because we can pinpoint the exact cause — this makes them extremely treatable. There’s a groundbreaking technology called Antisense Oligonucleotides (ASOs) that can silence mutations at the source. Since the first approved drug in 2016, ASOs have successfully halted severe diseases like Spinal Muscular Atrophy and Batten’s Disease. Unlike traditional drugs that target proteins (the hardware), ASOs target at the RNA level (the code). These have repeatable properties, making customization remarkably easy. By modifying a few characters of code, without changing the chemistry or dosing, you can design an ASO to target any mutation. We live at a unique moment in time where a child can be treated with a personalized ASO — an “N of 1” treatment. Last year, Dr. Timothy Yu at Boston Children’s Hospital created the first N-of-1 ASO, skipping the lengthy clinical trial process.
Pharma is currently not set up to make money from these individual treatments — there’s no blockbuster drug to advertise, there’s no IP to protect. We have started a non-profit Lydian Accelerator to fill this gap and help accelerate this treatment for Lydia and others. No parent should go through what we’re going through. As computer scientists, we believe in open platforms. By open sourcing the processes, tools and data from the first few N-of-1s, we can empower any institute to create one. We can then build a shared database of efficacy and safety data — anyone performing an N-of-1 should be able to tap into this repository as long as they contribute back into it. With more data, we may be able to use algorithms to reduce or even eliminate lab work that constitutes the bulk of the costs today. With each treatment, we can reduce the time and cost for the next one.
We are early in our journey, but ambitious and learning more every day. We’re working with a world-class team across Boston Children’s, Stanford and Northwestern. As we make progress in our journey, we will work with our collaborators to open source everything from Lydia’s N-of-1— the process, costs, contracts, protocols, assays, cell lines and data.
This research is expensive today. We are fortunate to be part of an incredible tech community. Please consider donating and sharing our story with other benefactors in this community. If you are able to make a larger grant through a foundation or DAF, get in touch with us. Gifts are tax deductible and eligible for matching at most large employers.
P.S. Our tendency is to stay private on social media but we are opening up because Lydia’s story can help others. We will share our journey as best as we can. Please feel free to subscribe to this blog.