How an unsolved medical mystery became a life-saving breakthrough
How an unsolved medical mystery became a life-saving breakthrough
Courtney Crowder, USA TODAY NETWORKSat, April 18, 2026 at 9:30 AM UTC
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The coughing is so violent, so thunder sharp, that Dr. Mike Welsh, hears the deep, wet claps through the exam room’s closed wooden door and well down the hallway.
Their echo reverberates, the force of each choke conjuring a frame in painful contraction. One of those rare moments when sound has a feel.
Inside, a young girl, 7 or 8, is fighting for each breath.
When she’s not coughing outright, her shallow gasps rattle, emitting a craggy low-pitched moan. And as she hawks, she brings up a foul-smelling, custard-like phlegm. Scientific name: Pseudomonas aeruginosa.
Welsh, then a third-year med student on his pediatric rotation in the early 1970s, watches how she’s recruiting every muscle to inhale: chest, diaphragm, neck, pecs even. And, hand on her back steadying a stethoscope, he feels the extreme effort in each exhale.
“Cystic fibrosis,” read the notes scribbled on her chart.
Dr. Michael Welsh stands for a photo in his laboratory at the University of Iowa, Feb. 11, 2026.
A progressive genetic disorder in which thick, sticky mucus slowly drowns the lungs while destroying other vital organs, cystic fibrosis has no cure and, back then, no good treatments ― outside of punishing therapies that only moderately eased painful symptoms.
She’s probably not going to live into her teens, the attending physician tells Welsh after the exam. And if she does, well, she won’t make it out of her teens.
That little girl became Welsh’s personal index case. Her coughs and contractions were the impetus behind nearly 50 years studying chloride movement across the cells lining organs and body cavities, experiments that would be critical to cracking the medical mystery of cystic fibrosis.
Ultimately, Welsh’s research resulted in one of the most revolutionary health advancements of our time: a series of medications that transformed cystic fibrosis from a lethal diagnosis into a manageable condition.
For this work, Welsh and two colleagues won the 2025 Lasker Award, biomedicine’s most prestigious honor ― an accolade so distinguished it’s often referred to as the “American Nobel.”
William O’Neal II, pictured Jan. 30, 2026 at Dublin Underground in Iowa City, is a cystic fibrosis survivor.
“This medication, in no hyperbolic terms, saved my life,” says William O’Neal II, who was diagnosed with CF as a newborn and, at 20 years old, given three months to live unless he received a lung transplant.
As O’Neal was waiting for news of an available organ in 2019, his doctors called to say a series of medications had been approved to treat CF. They overnighted the pills to O’Neal’s door.
Within a few weeks of starting the treatments, O’Neal was walking without gasping and talking without pausing to gobble air.
“That was the first time I knew the drug was a miracle,” says O’Neal, 27, who is now a poetry fellow at the world-renowned Iowa Writers’ Workshop. “Like, it was a miracle.”
Before and after the medication felt similarly distinct to Grace Lidgett, a 21-year-old student studying marketing and graphic design at Grace College, Indiana.
“My lungs were just clearing these things that had probably been sitting in the bottom of them for forever,” she says of the first few days taking the pills. “It was all coming out at once, and then it was silence.”
Grace Lidgett works at Sidecar Coffee in 2025. Grace was diagnosed with cystic fibrosis as an infant.
Like many CF patients, Lidgett struggled to slow her breathing after any kind of exertion. But once prescribed the medication, she became a triple qualifier in Iowa's state high school cross-country and track competitions.
“When you are able to breathe in and get a full breath of air, it's like you're flying,” she says.
“It's like …,” she pauses, searching for the words. “Like a weight is lifted off your chest.”
Curiosity, collaboration lead to life-changing science
Cystic fibrosis is caused by a mutated gene that alters how a critical protein known as CFTR ― a merciful shorthand for cystic fibrosis transmembrane conductance regulator ― forms inside a cell.
Studying the structure and inner workings of defective CF cells, Dr. Welsh eventually pinpointed that chloride wasn’t passing through the cell membranes of CF patients.
Instead, chloride seemed to get stuck inside their cells, which was drawing water out of the airways and out of the lungs’ normally fluid mucus. Hence, the dehydrated, mucky phlegm in people with CF.
Using salt as his guidestar, Welsh first discovered that a healthy CFTR protein created a chloride channel, which acts as a little pipe through a cell membrane.
Like a cornerstone to liquid movement inside the body, this pore lets chloride, specifically, pass while batting away other electrolytes.
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But in people with CF, that protein creates a malformed channel or, in some cases, doesn’t make one at all.
“We learned there's lot of different mutations that can break CFTR,” Welsh says. “It's easy to smash.”
Dr. Michael Welsh, back, speaks to Steve Bullard about his research Dec. 4, 2025.
As Welsh’s team began to study possible fixes, he came across a Science magazine article in which a fellow researcher reported showing chloride movement in the experiments they were conducting on the broken CFTR protein.
Chloride movement would mean there was hope yet for the protein, that there was a possibility it could be fixed.
But his lab hadn’t seen anything of the sort, so he scoured the paper for what he could be missing. And in the “methods” section he found a clue.
“I realized they had done this in frog eggs,” he says.
If sentences could scream this one howled: FROG EGGS.
Welsh worked with those before. They’re kept incubated at a lower temperature than human cells — 18 degrees Celsius versus 37 degrees Celsius.
So Welsh and his team made the cells like they always did, but they put them into a colder incubator. 30 degrees. 26. 23. Colder and colder.
And they saw that as they lowered the temperature, the protein matured. It folded better. It journeyed to the cell’s surface where the channel could work.
It opened.
Welsh had proven that through cooling the cells, the protein could be rescued and the chloride channel restored. In the lab, at least.
“It was an observation that could easily have been overlooked: ‘It works in frog eggs,’” says Bijal Trivedi, whose book “Breath from Salt” traces the rise of cystic fibrosis’ treatments.
“It was that eureka moment that let others know, OK, maybe there is a way to fix this protein," she says. "And that basically opened up the playing field for drug discovery.”
'Duct tape': Research opens a channel, but more is needed
Since refrigerating people wasn’t a viable treatment, chemists and pharmacologists needed to create a small molecule that could replicate what happened in the cold. And enormous advancements in robotics, computer analytics and molecular chemistry in the early 1990s meant drug companies were primed to meet that moment.
Spending hundreds of millions of dollars on iterative development over two decades, Vertex Pharmaceuticals created four drugs that function in part like “duct tape,” says Welsh, “holding things together.”
In the simplest terms, the drugs essentially turn on the chloride channel, allowing salt and water to move and mucus to clear from the lungs and other organs.
In 2012, the first medication was approved, which repaired the protein mutation for about 5% of CF patients.
Grace Lidgett runs through rural Tama County in 2025. Grace was diagnosed with cystic fibrosis as an infant, and through therapies that included Ofkambi and now Trikafta, has been able to live an active life that included running on her high school track and cross country teams.
Slowly, more drugs were approved to help more people: Orkambi in 2015, Symdeko in 2018 and Trikafta in 2019, which ultimately treats up to 90% of CF patients in the U.S.
“This is a win, but we’re not done yet,” says Welsh, whose lab is researching treatments for the remaining 10% of CF patients not eligible for medication and, ultimately, hunting a cure.
For Lidgett, who now runs for fun, every deep breath is proof positive that research, when funded and supported, can uplift, empower and reshape patients’ futures.
“I am so incredibly grateful for those researchers and scientists who just continue to work,” she says.
“I hope my life is a walking testimony of what they've done.”
Courtney Crowder is the Register's Iowa Columnist and a senior writer. Please share stories and tips at [email protected] or 515-284-8360.
Watch Giving Back Breath documentary
Go deeper into Dr. Welsh’s revolutionary research with “Giving Back Breath”, a 20-minute documentary that follows this dogged scientist as his meticulous experimentation leads to the remarkable breakthrough that transforms a lethal diagnosis into a manageable condition for patients like Grace Lidgett and William O’Neal II.
This article originally appeared on Des Moines Register: Cystic fibrosis was a mystery. One discovery unraveled its secret.
Source: “AOL Breaking”
