Three Aboriginal children hold the key for unlocking important medical insights.

Transcript

I'd love to share with you a story, a story about a gift, a gift that keeps on giving, a gift from one of the most remote places in the world, in the western desert of Western Australia, a gift, a gift from three remarkable Aboriginal children, who each in turn were born with a devastating condition, a condition affecting their hearts, their brains, their breathing, their learning. They then ultimately went on to develop intellectual disability and seizures. A gift that transverses time and transverses our planet.

These three children unlocked incredible medical insights. They were discovered to have a rare condition, a glitch into a change in a single chemical in a single gene, a gene called MTOR. This change made the gene work way too much. It was overactive and that caused chaos throughout their bodies.

When we first found this gene change, there was no map. There was no map to compare this gene change against for Aboriginal people, to know whether or not this was an abnormal gene change.

So then we had to go on a remarkable journey. We searched all over the world to find people that could prove whether or not this gene change was in fact the cause of these children's condition.

After circling the world, we kind of landed in our backyard. We landed on our own country with an immunology lab. They proved that that gene in fact did work far too much in experiments in cells in the laboratory. But much more importantly, they also showed that if we gave a commonly used medicine, a cheap medicine with a known side effect profile, that we could reverse the effect of that faulty gene in those cells.

Suddenly, we not only knew definitively what the cause of this children's condition was but we immediately had an option for their treatment using an existing drug, something we could take off the shelf. We didn't need to go through a billion dollars and 20 years of drug development. We could use that right now.

This condition ultimately came to be known as Smith‑Kingsmore Syndrome.

With the permission of the family, we published this information to see if there are other families around the world. And then a chain reaction of events occurred as others were diagnosed around the world, a bit like cousins around the world for these Aboriginal children.

Then there were new insights. In Germany, two siblings were identified with the condition, teenagers. And they had bowel polyps. That's very unusual in teenagers. Bowel polyps are the precursor of bowel cancer.

So, suddenly, we didn't potentially only have a treatment for seizures, intellectual disability, but also potentially bowel cancer. Again, something that was off the shelf.

Not only does this gift give internationally, it gave locally to our community in Western Australia. We solved this medical mystery using genomic sequencing back in 2013. It was the first time we had used that as a clinical test. That then gave our health system and it gave the Aboriginal communities the trust and the confidence to be able to do that more. It set up our Rare and Undiagnosed Diseases Diagnostic Service and, ultimately, what became the Undiagnosed Diseases Program.

The gift keeps on giving, because that Aboriginal family taught us how to provide the best medical care, how to embrace Aboriginal ways of knowing, being and belonging to help everybody.

We then took those principles to design how we provided care coordination for people with rare and undiagnosed diseases, care coordination across all of what it means to live a life in children, be it health, education, disability and social services.

So, to that Aboriginal family, to those three children, those incredible, vulnerable, special, powerful children from one of the remotest corners of the earth.

Thank you.

Having become a mother at 18, this is supposed to be the year Katie Stevens figures out who she is — but then she discovers her 12-year-old son is terribly ill.

TRANSCRIPT

12 years ago, my day‑to‑day worries included things like, did the kids make it to school on time? For the first time ever, all three of my kids were in school. Did the laundry get done? Did I get up at 5:00 AM for my six‑mile run?

I remember telling my friend this was going to be the year that I get some rest and I figure out who I am. I'd been a mother since I was 18 years old and I was excited to think about going back to school.

My oldest, Riley, was born a perfectly healthy little boy. He grew into a very strong 11‑year‑old who is running 5Ks alongside me. That summer, we started to notice some abnormal bruising. Things like seatbelts would leave marks across his neck. His friends who played soccer, their legs looked fine, but Riley's were littered with bruises.

We took Riley to his annual visit in August and his pediatrician assured me that it was okay to wait for lab tests and that we didn't have a history of cancer in our family, so it was okay. Things were going to be okay. He scheduled labs to be drawn in October.

Over the next few weeks, we started to notice little things, like a cough that just wouldn't go away or, when he went for a run with his Dad, he said he just felt really tired. My gut was telling me there was something to be worried about, but I brushed it aside because his doctor said it was okay. What did I know? I was just a mom.

The night before his blood draw, we watched a St. Jude's commercial. I looked at my husband and I said, “I think something's really wrong with Riley.”

We pulled up to the lab and I prepped Riley. It was just going to be one poke. I would hold his hand and we’d go get one of those $1.50 hotdogs from Costco.

They drew 14 vials of blood. We got home that afternoon and Riley went outside with the kids to play. And he ran in and asked something. His face was sweaty, his hair was sweaty but he was smiling, but he was blue.

I put my ear to his chest to make sure he was breathing okay, because I thought for sure that was it. Little did I know, those 14 vials of blood had drained him of the already dwindling blood supply.

I called his doctor. He told me to get Riley to the ER. I didn't know then that he had already seen the results of Riley's blood draw.

The ER drew labs again. They looked at me and said, “You need to get him in the car. You need to get him over to the next state,” which was Washington, into the children's hospital because my rural Idaho hospital couldn't handle what was happening to him.

The doctor at the children's hospital pulled my husband and I into a tiny room away from Riley and told us the devastating news that our child who had been hiking mountains over the summer either was in bone marrow failure or had cancer. His body was no longer equipped to sustain life.

Less than 12 hours since we were eating a hotdog at Costco, we were admitted to the hematology‑oncology floor.

As we got settled in for the night, I was tucking him into his hospital bed. How had I not noticed how pale he had become? His white skin matched the sheets and the hospital lighting and all I could see were his blue eyes that were full of fear.

“Please sleep with me in bed tonight, Mama. I'm really scared.”

My only worry now was that I needed to save my child's life.

The next morning, my husband came and I asked if I could step into the hallway. I covered my mouth and I sobbed and I shook and I broke. I couldn't let him see me like this. I couldn't make it so scary. How was I going to hide that I knew he could die?

Riley was diagnosed with severe aplastic anemia, a rare bone marrow failure disorder. The cause was unknown, but our family history, again, didn't make anyone think it could be genetic.

Riley had had two options at survival. Two. One was an immunosuppressive therapy that should train his body to quit attacking itself. The trick, he couldn't have an underlying genetic condition for it to work.

The second was a stem cell transplant. It was much more dangerous and his best chance at life would be if he had a sibling match. The problem, neither one of our children was a match for him.

So, because there was no known genetic issue, because testing hadn't been run, and he didn't have a sibling match, immunosuppressive therapy was ordered to start on Halloween.

Here's the thing. My deep knowing knew we were going to be headed to stem cell transplant if this didn't work. And my deep knowing knew that my thriving child didn't go from perfectly healthy to dying. That just doesn't happen.

My life was so different from where it was three weeks prior. I was still worried about laundry, but this time I was delegating it to whoever was able to help us at the time. I was coordinating hospital dinners with my family just to try to keep some sense of normalcy.

I was fighting insurance companies and I was fundraising just to make ends meet and to make sure my littles could stay in swim lessons.

16 weeks would have to go by before telomere length was performed and showed that Riley did have a genetic condition. Remember the immunosuppressive therapy? Well, it was a fucking nightmare to watch him go through and it was never going to work.

Telomeres. This was a word that had never crossed my lips. My 11‑year‑old knew it from middle school biology and I started realizing right then and there it was up to me to understand all the nuances of the science that was happening inside of him and the treatment available to him, because you know what? Doctors have a lot of patients, but I only had one Riley.

Telomeres were the word that changed my universe. They're the protective end cap of our DNA and they work like the aglet of a shoelace. They keep our DNA from unraveling. When we're born, ideally, they're longer. And as we age, they shorten. Riley’s are what you would expect in an 80 to 90‑year‑old person.

In the midst of all this, we're trying to find resources. One co‑pay was $800 a month. Our case manager was amazing and he tried to prepare me. He said, “You're going to be in this ocean of cancer and aplastic anemia is this little, tiny island.” And now we had the diagnosis of telomeres and we were on a rock, stranded. Alone.

This was the dance I found myself in for the rest of Riley's journey. Patients with short telomeres can't have a standard stem cell transplant protocol. Alkylating chemos and radiation destroy them, and the data showed there was very few that survived it.

They told us that Riley had a donor identified, a 23‑year‑old male who wasn't answering the phone. To me, the most logical thing to do was to tell them to call his mom.

In this time of sheer chaos, Riley's body was somehow giving us time to find the right path. We were connected to the patient advocacy group via Facebook and they were hosting a camp in Maine, where experts from around the world would be and other families like ours would be there as well. We went and we were welcomed with open arms. We were no longer alone.

We met a doctor who had designed a protocol, stem cell transplant, for patients with short telomeres. The clinical trial already had patients that had gone through it and it showed that they were doing very well.

Coming home, I was so excited to tell our hematologist what I had learned. Riley met all the criteria for this clinical trial. We knew it was a risk, but all transplants are a risk and I wanted to spare him the complications that I knew he would endure due to his genetic condition.

He looked at me and smiled. I think we're just going to stay with the plan.

Riley doesn't show the typical signs of someone with a telomere issue. This time, though, I wasn't going to listen just because they told me to. This time, my gut told me that this was the treatment that was right for Riley.

I moved Riley 3,000 miles from home. I left behind my other children and my husband. Riley was number six in the world to undergo this clinical trial. We Life Flighted the now 24‑year‑old’s marrow from Germany. He picked up the phone.

Riley's body accepted his cells as his own and, now, nine years later, we have never been back in a hospital in all that time.

A year later, we were back to status quo, but for me it was too quiet. To my surprise, I had found out about myself. Through this process, I learned that I really understood and enjoyed the complexities of genetics. Helping people that were on that rock felt like it was my calling. I was asked not to just help but to step into the role as the first executive director of the leading international research and advocacy patient organization for telomere biology disorders.

Today, I worry if someone has received proper diagnostic testing, if a clinical trial is developed in an equitable and accessible way. I worry about grants and fundraisers and sell lines. I worry if Riley and Olivia are doing okay in college. I worry if Ethan is enjoying his senior year. Oh, yeah, I had another baby during this. Grayson is 11 and he knows what telomeres are too.

Some things never change. I still need to do the laundry, I still need to run, and Costco hotdogs are still $1.50.

Thank you.