During my first 2 years of medical school, our professor provided a fascinating lecture series on the clinical manifestations of several heritable maladies, including cystic fibrosis (CF). At the time, I had no idea that a rare CF mutation was hiding in my own DNA, or that my family would soon join others in a fierce battle against what was then an undefeatable foe.
I recently ran into one of my CF fundraising friends who told me that one of “our kids” was about to get married. I was reminded of a time when we didn’t dare dream of future weddings or career paths. The decades of hard work that got us here is a story that deserves to be told.
The years have not diminished my recollection of several disturbing black-and-white images from that med-school lecture. Photos of frail children tethered to oxygen tanks flanked by medical personnel. Autopsy specimens, including flabby failing right hearts from pulmonary hypertension and a boggy inflamed pancreas. All emphasized the common denominator of CF pathology: a thick, slimy mucus that eventually chokes the normal physiology of many organs.
As early as the 1500s, a European proverb warned, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” The disease was first named by Dorothy Andersen who pivoted to pathology after being rejected for a surgical residency because she was a woman. She noted that the pancreatic tissue of the children who died was riddled with cysts.
In 1948, the New York City heatwave brought many dehydrated children with CF to Andersen’s hospital. From the observation that the tiny fingerprints on their water glasses comprised mostly sodium chloride came the diagnostic sweat test. Prior to formal testing, physicians would actually lick the arms of children to subjectively assay for “salty sweat” — a practice that would certainly raise eyebrows today.
The initial 5-year life expectancy was pushed to age 18 by the time I finished med school. In 1989, former National Institutes of Health director Francis Collins, MD, PhD, and colleagues at the University of Michigan identified the relevant gene, CFTCR (cystic fibrosis transmembrane conductance regulator). This gene encodes the protein that regulates the flow of chloride ions across the cell membrane and preserves salt and water balance throughout the human body. Despite that magnificent discovery, this autosomal recessive disease continued to limit life expectancy to the early 30s for several years.
An Ominous Family Legacy
It was the birth of my brother Shane’s first child, Stephanie, that would begin my family’s 30-plus–year odyssey to outsmart CF.
Shane and Lori Walton with baby Stephanie.
Shane Walton, a successful Kentucky realtor, feigns boredom with nearly all things medical (probably to annoy me), but if you ask him about our mutation, he will immediately recite, “2789 +5 G>A”. He committed that to memory because Stephanie inherited the Walton mutation, along with the more common one, F508del, from her mother Lori.
Stephanie’s diagnosis immediately sent me licking the arms of my daughters and requesting sweat chloride tests. They harbored only the Walton mutation — a relief, but one that requires prenatal testing of prospective fathers of their future children.
Shane and I started digging into our family history. Our maternal grandmother, who died at age 60, had required oxygen from her late 20s onward, but our mother was negative for any CF mutation. We learned that our dad’s maternal aunts died at age 2 and 21 years of “lung illnesses” and two uncles died shortly after birth. Their deaths were ascribed to “consumption” at the time, a diagnosis we now find doubtful.
About a decade after we learned of Stephanie’s diagnosis, I spotted my 55-year-old cousin in the waiting room of my hospital. It had been a while since I’d seen Keith, who was always laughing and seemingly in good health. Now, he sat emaciated and tethered to an oxygen tank. “I’m seeing a lung specialist,” he said. I reminded him gently that we have CF in our family. “They are testing me for that,” he replied. The diagnosis landed in his mailbox 2 weeks later, on the day of his funeral.
For Shane and Lori, their daughter’s disease carried terrifying unknowns. There were only a handful of reported cases of this particular mutation, globally. It was suggested by some that it might have a “watered down” effect, and carriers would not develop significant pulmonary complications. But experts cautioned us that Stephanie would eventually get very sick.
Fundraising and Our Expanding CF Family
Shane and Lori were determined to do all they could to avert that. Thus began our connection with the Cystic Fibrosis Foundation, created in 1955 by Didi Sharples, MD, a pediatrician who had two children with CF. We got involved with the Kentucky/West Virginia chapter. By word of mouth, we found other families in our area, and together we developed a network to fight for our CF kids.
Clint Neal with his mother Tammi, and his grandmother Jewel Estes.
One of the first formal fundraisers was held in our backyard, complete with a bouncy house, face painting, music, and a silent auction. Here we met Clint Neal, then about 6 years old. His mother, Tammi, and her parents had been fundraising for years but found new strength in numbers.
Our other CF kids included Spencer Dickson, whose parents Mark and Amy arranged for family-friendly comedians to perform at our local Plaza Theatre, and Taylor Dillingham. Taylor’s parents, Marcia and Charles, brought in multiple auction items and sold raffle tickets. I wrote a children’s book and recorded two albums with Shane’s help. Lori baked and ran a food truck. Every year when we felt that autumn chill we set to work. Together we raised over $100,000 dollars for the CF foundation. We felt we were winning against this terrible disease, but CF had other plans.
During Spencer’s teenage years, he hit a particularly rough patch. His forced expiratory volume in 1 second (FEV1) abruptly declined to the 20% range. His mother wanted him to stop his new drug Orkambi (lumacaftor-ivacaftor) — a medication that had helped most patients but, for reasons unclear, Spencer couldn’t tolerate it. He spent 2 weeks in the hospital and several more after that trying to get back to his baseline.
My niece Stephanie underwent cholecystectomy, despite her surgeon refusing to believe that a teetotaler could have pancreatitis. Her honeymoon in Nuevo Vallarta was interrupted by a second bout of pancreatitis that required her to go directly from the airport to the hospital. There she was told repeatedly “This has nothing to do with CF,” until a CF consultant insisted, “This has everything to do with CF.” After that, hospital policy required a CF specialist consult for any CF patient no matter their admitting diagnosis.
Taylor Dillingham
Taylor spent a month in the hospital and even received a visit from the Make-A-Wish Foundation. “I didn’t even know what to ask for,” she told me. She confessed that during an admittedly rebellious phase, she stopped all of her medications because she “didn’t see the point.” She got herself back on track but continued to struggle with frequent bouts of pneumonia. “I was on antibiotics for most of a year,” she said.
Clint required a peripherally inserted central catheter and was struggling. His pulmonary function tests and BMI were plummeting. “At one point, I didn’t even know how to define the word ‘appetite,’” he told me. Then his half-sister, who also had CF, died after a double lung transplant.
Our community of CF families was heartbroken. It was as if we were caught up in a horrifying chapter of the old German fairytale “Rumpelstiltskin.” Our fundraising was spinning gold, but like that evil goblin, CF hid silently in the shadows, waiting to steal the children during what should have been the prime of their lives.
True Game Changers
Preston Campbell, III, MD, the former Vanderbilt pulmonologist who treated my niece, served as the president and CEO of the Cystic Fibrosis Foundation from 2015 to 2019. During his tenure and in collaboration with multiple drug companies, 12 therapies appeared on the horizon. Four are gene modulators that treat the basic genetic defect. Trikafta (elexacaftor, tezacaftor, and ivacaftor), which was approved by the US Food and Drug Administration (FDA) in 2019, benefits 90% of patients with CF. In 2024, the FDA approved Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) which will treat an additional 31 mutations.
The effects have been profound: The number of CF-related lung transplants declined dramatically in 2020. Thankfully, our “CF kids” all started Trikafta immediately upon approval.
Spencer Dickson with his wife, Ally.
After taking his first dose, Spencer went to lunch with some friends. “I didn’t know what in the world was happening. I guess it was ‘the purge,’” he said, with a chuckle. He had to leave the table to cough up “gunk” and did so for 4 days. The improvement in his pulmonary function tests (PFTs) was nearly immediate. He now has a great appetite and is a full-time HVAC worker and it was news of his wedding that prompted this essay.
“I will fight ‘65 roses’ with you until the day I die,” his wife, Ally, said as part of her wedding vows, invoking the mispronunciation of CF that young children often use for the disease. Hearing that punched me in the gut as I watched their wedding video. Ally and Spencer plan to start a family soon (through intrauterine insemination), something that wasn’t considered possible 20 years ago.
Stephanie with her daughter, Lilabet.
Stephanie had no significant pulmonary pathology and has had no recurrence of pancreatitis. She is married and has a healthy 21-month. She marveled at how easy it was to conceive on Trikafta, describing their efforts as “one and done.” The CF clinic she attends has transformed from a waiting room full of frail young patients, some of whom were on oxygen, to healthy-looking young adults. Many are new moms with children on their laps.
Taylor Dillingham and one of her many pets.
Taylor, who previously didn’t want to “waste” what life she had left studying, is now enrolled in pre-vet studies. She too has gained weight, and for the first time she knows what it feels like for her lungs “to completely fill with air.” She has six cats and two dogs and is fostering two additional felines. “I’m now over my cat limit,” she quipped.
But there are still challenges.
“I didn’t get the bounce in my PFT that others did”, Clint told me. He is still sitting at an FEV1 in the upper 60s, uncertain whether this is due to his genetics, scarring from severe chronic disease, or a combination of both. It hasn’t stopped him from applying for a PhD program the University of Kentucky.
Coverage Challenges
Clint and Tammi at his college graduation.
For others, drug coverage is a constant concern. Like many CF patients, Clint was placed on Medicaid soon after birth. He was advised by a lawyer that if he became gainfully employed with good prescription coverage, he could not be guaranteed access to the medications if he lost his job. Taylor knows that issue well. She switched jobs and spent an entire year off meds until she could obtain coverage.
Ongoing disparities in access are unnecessary. According to public health researchers, the production cost for triple therapy with Trikafta is $5676 per year — 90% lower than the US drug price. They estimate that every eligible CF patient worldwide could be treated for a total of $489M per year but the annual cost at US list price would be $31 billion. Unless government or third party payers agree to coverage, patients are left without therapy.
A recent email update I received from the CF Foundation acknowledged that many are still waiting for their breakthrough treatment. More worryingly, the foundation anticipates that the development cost of a new mutation modulator may be 10-fold higher than a decade ago.
The current president and CEO noted that they have fielded more than 7000 calls from CF families with questions about insurance, access, and other issues. This speaks to the complicated pathway that patients with CF and their families must navigate.
We have come light years from licking the arms of children to a supernova of successful genetics-based therapies. In Rumpelstiltskin, the Queen used all her resources to learn the goblin’s name so she could keep her child.
Today, because so many learned so much about this devastating disease, our families get to keep our “CF kids”. They are living, breathing testaments to the fact that bench research can be fueled by bake sales, sponsored walks, chili suppers, and silent auctions.
Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband and daughters, and sidelines as a backing vocalist for local rock bands. Her Heartfelt column was the 2022 northeast regional gold and national silver Azbee award winner.
COMMENTARY
Fighting the Rumpelstiltskin of Diseases and Largely Winning
DISCLOSURES
| February 20, 2025During my first 2 years of medical school, our professor provided a fascinating lecture series on the clinical manifestations of several heritable maladies, including cystic fibrosis (CF). At the time, I had no idea that a rare CF mutation was hiding in my own DNA, or that my family would soon join others in a fierce battle against what was then an undefeatable foe.
I recently ran into one of my CF fundraising friends who told me that one of “our kids” was about to get married. I was reminded of a time when we didn’t dare dream of future weddings or career paths. The decades of hard work that got us here is a story that deserves to be told.
The years have not diminished my recollection of several disturbing black-and-white images from that med-school lecture. Photos of frail children tethered to oxygen tanks flanked by medical personnel. Autopsy specimens, including flabby failing right hearts from pulmonary hypertension and a boggy inflamed pancreas. All emphasized the common denominator of CF pathology: a thick, slimy mucus that eventually chokes the normal physiology of many organs.
As early as the 1500s, a European proverb warned, “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” The disease was first named by Dorothy Andersen who pivoted to pathology after being rejected for a surgical residency because she was a woman. She noted that the pancreatic tissue of the children who died was riddled with cysts.
In 1948, the New York City heatwave brought many dehydrated children with CF to Andersen’s hospital. From the observation that the tiny fingerprints on their water glasses comprised mostly sodium chloride came the diagnostic sweat test. Prior to formal testing, physicians would actually lick the arms of children to subjectively assay for “salty sweat” — a practice that would certainly raise eyebrows today.
The initial 5-year life expectancy was pushed to age 18 by the time I finished med school. In 1989, former National Institutes of Health director Francis Collins, MD, PhD, and colleagues at the University of Michigan identified the relevant gene, CFTCR (cystic fibrosis transmembrane conductance regulator). This gene encodes the protein that regulates the flow of chloride ions across the cell membrane and preserves salt and water balance throughout the human body. Despite that magnificent discovery, this autosomal recessive disease continued to limit life expectancy to the early 30s for several years.
An Ominous Family Legacy
It was the birth of my brother Shane’s first child, Stephanie, that would begin my family’s 30-plus–year odyssey to outsmart CF.
Shane Walton, a successful Kentucky realtor, feigns boredom with nearly all things medical (probably to annoy me), but if you ask him about our mutation, he will immediately recite, “2789 +5 G>A”. He committed that to memory because Stephanie inherited the Walton mutation, along with the more common one, F508del, from her mother Lori.
Stephanie’s diagnosis immediately sent me licking the arms of my daughters and requesting sweat chloride tests. They harbored only the Walton mutation — a relief, but one that requires prenatal testing of prospective fathers of their future children.
Shane and I started digging into our family history. Our maternal grandmother, who died at age 60, had required oxygen from her late 20s onward, but our mother was negative for any CF mutation. We learned that our dad’s maternal aunts died at age 2 and 21 years of “lung illnesses” and two uncles died shortly after birth. Their deaths were ascribed to “consumption” at the time, a diagnosis we now find doubtful.
About a decade after we learned of Stephanie’s diagnosis, I spotted my 55-year-old cousin in the waiting room of my hospital. It had been a while since I’d seen Keith, who was always laughing and seemingly in good health. Now, he sat emaciated and tethered to an oxygen tank. “I’m seeing a lung specialist,” he said. I reminded him gently that we have CF in our family. “They are testing me for that,” he replied. The diagnosis landed in his mailbox 2 weeks later, on the day of his funeral.
For Shane and Lori, their daughter’s disease carried terrifying unknowns. There were only a handful of reported cases of this particular mutation, globally. It was suggested by some that it might have a “watered down” effect, and carriers would not develop significant pulmonary complications. But experts cautioned us that Stephanie would eventually get very sick.
Fundraising and Our Expanding CF Family
Shane and Lori were determined to do all they could to avert that. Thus began our connection with the Cystic Fibrosis Foundation, created in 1955 by Didi Sharples, MD, a pediatrician who had two children with CF. We got involved with the Kentucky/West Virginia chapter. By word of mouth, we found other families in our area, and together we developed a network to fight for our CF kids.
One of the first formal fundraisers was held in our backyard, complete with a bouncy house, face painting, music, and a silent auction. Here we met Clint Neal, then about 6 years old. His mother, Tammi, and her parents had been fundraising for years but found new strength in numbers.
Our other CF kids included Spencer Dickson, whose parents Mark and Amy arranged for family-friendly comedians to perform at our local Plaza Theatre, and Taylor Dillingham. Taylor’s parents, Marcia and Charles, brought in multiple auction items and sold raffle tickets. I wrote a children’s book and recorded two albums with Shane’s help. Lori baked and ran a food truck. Every year when we felt that autumn chill we set to work. Together we raised over $100,000 dollars for the CF foundation. We felt we were winning against this terrible disease, but CF had other plans.
During Spencer’s teenage years, he hit a particularly rough patch. His forced expiratory volume in 1 second (FEV1) abruptly declined to the 20% range. His mother wanted him to stop his new drug Orkambi (lumacaftor-ivacaftor) — a medication that had helped most patients but, for reasons unclear, Spencer couldn’t tolerate it. He spent 2 weeks in the hospital and several more after that trying to get back to his baseline.
My niece Stephanie underwent cholecystectomy, despite her surgeon refusing to believe that a teetotaler could have pancreatitis. Her honeymoon in Nuevo Vallarta was interrupted by a second bout of pancreatitis that required her to go directly from the airport to the hospital. There she was told repeatedly “This has nothing to do with CF,” until a CF consultant insisted, “This has everything to do with CF.” After that, hospital policy required a CF specialist consult for any CF patient no matter their admitting diagnosis.
Taylor spent a month in the hospital and even received a visit from the Make-A-Wish Foundation. “I didn’t even know what to ask for,” she told me. She confessed that during an admittedly rebellious phase, she stopped all of her medications because she “didn’t see the point.” She got herself back on track but continued to struggle with frequent bouts of pneumonia. “I was on antibiotics for most of a year,” she said.
Clint required a peripherally inserted central catheter and was struggling. His pulmonary function tests and BMI were plummeting. “At one point, I didn’t even know how to define the word ‘appetite,’” he told me. Then his half-sister, who also had CF, died after a double lung transplant.
Our community of CF families was heartbroken. It was as if we were caught up in a horrifying chapter of the old German fairytale “Rumpelstiltskin.” Our fundraising was spinning gold, but like that evil goblin, CF hid silently in the shadows, waiting to steal the children during what should have been the prime of their lives.
True Game Changers
Preston Campbell, III, MD, the former Vanderbilt pulmonologist who treated my niece, served as the president and CEO of the Cystic Fibrosis Foundation from 2015 to 2019. During his tenure and in collaboration with multiple drug companies, 12 therapies appeared on the horizon. Four are gene modulators that treat the basic genetic defect. Trikafta (elexacaftor, tezacaftor, and ivacaftor), which was approved by the US Food and Drug Administration (FDA) in 2019, benefits 90% of patients with CF. In 2024, the FDA approved Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) which will treat an additional 31 mutations.
The effects have been profound: The number of CF-related lung transplants declined dramatically in 2020. Thankfully, our “CF kids” all started Trikafta immediately upon approval.
After taking his first dose, Spencer went to lunch with some friends. “I didn’t know what in the world was happening. I guess it was ‘the purge,’” he said, with a chuckle. He had to leave the table to cough up “gunk” and did so for 4 days. The improvement in his pulmonary function tests (PFTs) was nearly immediate. He now has a great appetite and is a full-time HVAC worker and it was news of his wedding that prompted this essay.
“I will fight ‘65 roses’ with you until the day I die,” his wife, Ally, said as part of her wedding vows, invoking the mispronunciation of CF that young children often use for the disease. Hearing that punched me in the gut as I watched their wedding video. Ally and Spencer plan to start a family soon (through intrauterine insemination), something that wasn’t considered possible 20 years ago.
Stephanie had no significant pulmonary pathology and has had no recurrence of pancreatitis. She is married and has a healthy 21-month. She marveled at how easy it was to conceive on Trikafta, describing their efforts as “one and done.” The CF clinic she attends has transformed from a waiting room full of frail young patients, some of whom were on oxygen, to healthy-looking young adults. Many are new moms with children on their laps.
Taylor, who previously didn’t want to “waste” what life she had left studying, is now enrolled in pre-vet studies. She too has gained weight, and for the first time she knows what it feels like for her lungs “to completely fill with air.” She has six cats and two dogs and is fostering two additional felines. “I’m now over my cat limit,” she quipped.
But there are still challenges.
“I didn’t get the bounce in my PFT that others did”, Clint told me. He is still sitting at an FEV1 in the upper 60s, uncertain whether this is due to his genetics, scarring from severe chronic disease, or a combination of both. It hasn’t stopped him from applying for a PhD program the University of Kentucky.
Coverage Challenges
For others, drug coverage is a constant concern. Like many CF patients, Clint was placed on Medicaid soon after birth. He was advised by a lawyer that if he became gainfully employed with good prescription coverage, he could not be guaranteed access to the medications if he lost his job. Taylor knows that issue well. She switched jobs and spent an entire year off meds until she could obtain coverage.
Ongoing disparities in access are unnecessary. According to public health researchers, the production cost for triple therapy with Trikafta is $5676 per year — 90% lower than the US drug price. They estimate that every eligible CF patient worldwide could be treated for a total of $489M per year but the annual cost at US list price would be $31 billion. Unless government or third party payers agree to coverage, patients are left without therapy.
A recent email update I received from the CF Foundation acknowledged that many are still waiting for their breakthrough treatment. More worryingly, the foundation anticipates that the development cost of a new mutation modulator may be 10-fold higher than a decade ago.
The current president and CEO noted that they have fielded more than 7000 calls from CF families with questions about insurance, access, and other issues. This speaks to the complicated pathway that patients with CF and their families must navigate.
We have come light years from licking the arms of children to a supernova of successful genetics-based therapies. In Rumpelstiltskin, the Queen used all her resources to learn the goblin’s name so she could keep her child.
Today, because so many learned so much about this devastating disease, our families get to keep our “CF kids”. They are living, breathing testaments to the fact that bench research can be fueled by bake sales, sponsored walks, chili suppers, and silent auctions.
Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband and daughters, and sidelines as a backing vocalist for local rock bands. Her Heartfelt column was the 2022 northeast regional gold and national silver Azbee award winner.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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