Matt and Kristen Wilsey consulted more than 100 doctors and scientists to identify their daughter Grace’s rare disease, persisting when suggested diagnoses didn’t seem quite right or when doctors had no answers at all. Finally genome sequencing ended their diagnostic odyssey—and made them crusaders for a better approach. They learned Grace had NGLY1 deficiency, which cripples an important protein that is supposed to clear extra sugar from her body and causes symptoms like developmental delays, hypotonia, and neurological abnormalities. Now they work through their Grace Science Foundation to fund research and find other NGLY1 patients in all corners of the globe, establishing a tiny community that could ultimately lead to better treatment. Along the way, they have become thoughtful about the lessons for others from their experience. We talked to Matt about what he learned, his advice for parents in similar situations, and how tech might eliminate this kind of story in the future.
You realized when Grace was born that something wasn’t right. Who drove the quest for answers, you and Kristen, or the doctors? What did you learn from this experience?
We were really driving it. When Grace was born it was an emergency C-section. I don’t know if it’s parent intuition or what, but I knew something was wrong. I kept calling the hospitalist over to say there’s something wrong here, and he kept checking Grace out and said that she’s fine. I think the natural procedure for these doctors is, let’s calm everybody down. It’s a lesson for everybody: you’ve got to push. It’s so important to be the squeaky wheel. Don’t wait a second because every second is valuable in terms of diagnosing something or maybe preventing something. At the end of the day, the doctors, the nurses, the system— they’re not set up to be able to follow each of their patients and make sure that all unanswered questions are answered. It really comes down to the actual people dealing with it every day to keep fighting.
That advice can be difficult for people who were brought up to believe their doctors, even when medical answers don’t feel right. What’s your advice for them?
One of the best things is getting second or third opinions. Any doctor who questions that or gets their feathers ruffled because of that: Goodbye, thank you very much, we’re going to find a doctor that wants to be more collaborative. Thankfully we fell into some really good relationships with some key clinicians [who] weren’t offended when we wanted to get second or third opinions or if we had additional thoughts about tests that we should order. A lot of that was borrowed from my time as a tech entrepreneur. A good idea can come from anybody in the organization. What separates tech companies from non-tech companies is that most of them are very flat. That’s what we really wanted to instill in our clinical team—it’s an equal seat for everybody.
Eventually you reached out directly to scientists. Was it hard to get their attention and help?
It really wasn’t, probably because my background was business development. There’s a lot I can’t do, but what I can do is reach out to people and try to build a relationship. I’d cold call or cold email people. I’d probably have done a little bit of research on their papers and why this might be relevant to them. Scientists are very open. They don’t get many shots on goal. How many times do you get to potentially translate your research into a treatment or a cure for another human being? When they see someone who’s motivated to jump into the deep end of their field and help them, they’re very receptive. Of course we do get blown off too.
Grace’s diagnosis came from sequencing her genome, which is still rare in medicine. How did you get it done, and why did that make you a sequencing champion?
After we had gone through basically every single test that we could run on Grace and striking out, I just got frustrated with throwing darts at the board in the dark. [Each test] required blood from Grace, which was stressful on her and on us, and then we’d have to go through the waiting game and then it was inconclusive. So I just said to our doctor, “I’d like to do whole genome sequencing.” He was like, “Oh, boy, we don’t know how to interpret the data.” I didn’t want to keep doing these one-off tests. Let’s get the data, let’s stick it on a hard drive. We might not be able to figure out what’s going on today or tomorrow or next year, but we will certainly in Grace’s lifetime figure out what this is.
You’d be amazed. I speak to parent advocates or patients, and their clinician still pushes back on [genome sequencing], which is just crazy to me because there is tremendous value in having a name for what you’re fighting. I’m a big fan of sequencing. I’d love to sequence the entire US population. I’d love to sequence every child that’s born in the United States.
A lot of people hear your story and think this isn’t something most parents could accomplish without the kind of resources and connections you have. What does that mean for other kids with rare diseases?
The cool thing is that it is a technology problem, which most people don’t really realize. People dismiss [us] as the exception, but I think we’re actually the tip of the spear. [Looking] back on a lot of different technologies— cell phones or automobiles or electricity in homes—there’s early adopters, people that do have the means or the connections to take advantage of those. But over time the technology becomes more efficient and cheaper so that millions and potentially billions benefit from it. Ultimately it’s about connections, which things like Facebook or LinkedIn or Google or Yahoo allow. The sharing and communication paradigm is changing. That’s really what this is: how do we harness this data and find clues that lead to diagnosis and treatments and then ultimately cures?
What are the most important investment areas for accelerating diagnosis of rare disease?
It’s next-generation sequencing. Companies like 23andMe and Counsyl [are] a great start because we’re consumerizing it, democratizing access which is critical because at the end of the day the customer always wins. That’s true of any industry. The customer is going to want this information and they’re going to want to have the transparency which we don’t have right now.
[We need] more efficient gene sequencing so that we could do a whole genome in an hour and we can analyze it the very next hour. Then it becomes 10 minutes and 10 minutes, then it becomes one minute and one minute. This goes hand in hand with that: we need secure platforms for sharing the data and comparing it. Also, what’s beyond the human genome? What about transcription or things like the microbiome?
Biomarker development is probably going to be a big area for the tech sector to get into— being able to quickly identify things in blood or urine, maybe even saliva or hair. I’m really excited about the possibility that we could identify something before someone’s symptomatic. Not only the human benefit, which is invaluable, but also we should be able to measure the business side of reducing those hospitalizations. It’s our fiduciary obligation to lower these health insurance costs.
This transition to a more personalized healthcare is really changing the idea of the paternalistic centralized system. It all comes down to technology. I’d encourage scientists and doctors to be entrepreneurs—it’s going to help all of us.
Matt Wilsey spoke at the Techonomy 2014 conference.