In the quiet corridors of the University of Iowa’s Carver College of Medicine, Michael J. Welsh, MD, has spent nearly five decades unraveling the deadly mechanics of cystic fibrosis, a genetic scourge that once consigned children to early graves. His discoveries—proving the CFTR protein functions as a chloride channel regulated by phosphorylation and ATP—laid the groundwork for modulator drugs that now treat about 90% of patients, transforming a fatal diagnosis into a manageable chronic condition.

Welsh’s journey began in the 1970s as a medical student, haunted by the image of a young girl gasping through persistent coughs, her sentences clipped by breathlessness. "Welsh’s encounter with this girl is burned in his memory. It motivated him to find a way to impact the lives of patients with this disease," reports Medicine Iowa. By the 1980s, his team showed CF disrupts chloride movement in lung airways, impairing bacterial clearance—a finding that predated the 1989 CFTR gene discovery by four years.

Post-gene identification, Welsh’s lab dissected CFTR’s role, classifying mutations into categories like defective processing, gating, and conductance. This framework enabled targeted therapies. "Beginning in the early 1990s, Welsh and his colleagues revolutionized the understanding of cystic fibrosis by demonstrating that the CFTR protein is a chloride ion channel," notes the University of Iowa Carver College of Medicine.

From Ion Channels to Industry Partnerships

Welsh’s insights propelled collaborations with Vertex Pharmaceuticals. Paul A. Negulescu’s team developed correctors and potentiators, culminating in Trikafta (elexacaftor/tezacaftor/ivacaftor), approved in 2019. This triple therapy addresses the common ΔF508 mutation, restoring CFTR function. Patients report dramatic gains: lung function surges, hospitalizations plummet, and life expectancy for newborns nears normal levels—up to 80 years.

"The dramatic improvements for people with cystic fibrosis have exceeded my hopes," Welsh told the American Medical Association. For the Denison twins, Maren and Berne, Trikafta meant ditching daily therapies. Maren, eligible in a 2018 trial, saw immediate relief; Berne followed post-FDA approval. Now 21, they pursue college degrees, milestones unthinkable decades ago, as detailed in University of Iowa Magazine.

Earlier modulators like Kalydeco (2012) targeted gating mutations, thanks to patients like Catherine ‘Kay’ VanThournout, who contributed cells despite dying at 58. UI Health Care, Iowa’s sole accredited CF center, offers trials and comprehensive care.

Awards Cement a Legacy of Persistence

Welsh’s impact drew biomedical accolades: the 2022 Shaw Prize, 2025 Canada Gairdner International Award, and 2025 Lasker-DeBakey Clinical Medical Research Award—America’s Nobel—for the triple-drug regimen. He shares the Lasker with Jesús ‘Tito’ González (ex-Vertex) and Negulescu. "To win the Lasker-DeBakey Award is an extraordinary achievement, and Mike Welsh is fully deserving," said UI Dean Denise Jamieson in UI Health Care.

The Lasker Foundation praised Welsh for illuminating CFTR defects, opening doors to small-molecule fixes. Previously, treatments like postural drainage—pounding chests upside down—merely eased symptoms. Median survival hovered below 30; now, adults outnumber children with CF.

Welsh pioneered CF pigs, the first non-rodent mammal model, mimicking human disease for testing. "I benefited from the freedom to chase after these problems at the University of Iowa," he reflected in UI Health Care.

Patient Transformations Fuel Momentum

Grace Lidgett breathes freely post-Trikafta, defying expectations, per UI Health Care. Anthony Fischer, UI CF specialist, notes patients stabilize for years without hospitalization. A documentary, ‘Breath by Breath,’ premiered September 30, 2025, showcasing stories.

"Trikafta was a huge milestone because it showed us that we could transform the disease for most people," Negulescu said in The Scientist. Vertex’s Alyftrek, a newer triple combo, expands options.

Costs challenge access; Vertex ended some compassionate programs. Yet, "Where we are now exceeds my hopes. But we are not done yet. There are still around 10% of people with CF who can’t benefit," Welsh urged in EurekAlert.

Unfinished Work Targets the Remaining 10%

About 10% with rare mutations lack effective modulators. Welsh co-founded cystetic Medicines; ABCI, a molecular prosthetic, restores function in trials led by UI and Carle Illinois, per Carle Illinois College of Medicine. UI-UIUC partnerships test it on patient cells.

Gene therapies and next-gen modulators like VX-121 combos enter trials (UCSF). Welsh eyes neuro links: CFTR work informs Parkinson’s, Alzheimer’s protein studies, as in Des Moines Register.

"The arc leading to effective therapies begins with description of a disease, progresses through discovery of fundamental mechanisms, and proceeds through development of treatments," Welsh said in Medicine Iowa. His rural Iowa roots—painting barns, raising pigs—instilled grit, crediting patients, mentors, and Iowans.

Precision Medicine’s Broader Echoes

Welsh’s model—basic science to bedside—redefines genetic diseases. From mist tents to pills doubling survival, CF exemplifies translational triumphs. "Mike Welsh’s work exemplifies how fundamental science—driven by curiosity, collaboration, and purpose—can lead to transformative innovations," Jamieson affirmed.

Global impact: 100,000 affected worldwide see hope. Ongoing UI research, via Pappajohn Biomedical Institute, pushes boundaries. As Welsh trains successors, his lab remains a beacon for the untreatable 10% and beyond.