Legacy of Changing Medicine: Cystic Fibrosis

Columbia University Irving Medical Center

As far back as the 15th century, a European proverb cautioned parents: “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon will die.” The taste of salt on a child’s skin was known to herald an unavoidable death preceded by rasping agony. Parents commonly believed their children had been cursed by witches.

Today, we know that this folklore spoke of the genetic disease cystic fibrosis (CF). Before the discovery of CF and ensuing advancement of care, most children with the disease didn’t survive past age 5. Estimates put the number of patients currently living with CF at more than 70,000 worldwide, with thousands of dedicated physicians, researchers, and fundraisers devoted to their cause.

The modern history of CF begins in 1935, in a basement pathology lab at what was then called the Columbia-Presbyterian Medical Center.

A determined pathologist’s curiosity and her ensuing investigation led to a landmark discovery-a revelation that would alter the lives of millions and launch a decades-long quest to turn the tide against a childhood death sentence.

The Trailblazer

For her time and place in history, Dorothy Hansine Andersen was as rare as she was brilliant. When only some 5% of practicing physicians in the United States were women, she held both an MD degree (from Johns Hopkins University) and a Doctor of Medical Science degree (from Columbia). She was equal parts trailblazer and firebrand. A biographical collection of notable American women notes that “she fought valiantly for professional equality, spoke out against sex discrimination when colleagues remained silent, and refused to pattern her life according to others’ ideas of what was suitable for a lady.”

After she was rejected for a surgical residency elsewhere because she was a woman, Andersen earned a position as a pathologist at Babies Hospital (now NewYork-Presbyterian Morgan Stanley Children’s Hospital). It was there she encountered her first case of cystic fibrosis in 1935.

Doctor sitting for a portrait
Dorothy Hansine Andersen

While performing an autopsy of a 3-year-old girl diagnosed with celiac disease, Andersen found the patient’s lungs in grisly condition and the pancreas riddled with fibrous cysts. Andersen took to the Columbia University library and in a broad study of her peers’ research found records of similar oddities in celiac cases. She began her own research, writing the authors of journal articles and requesting pancreatic tissue samples.

In 1938, Andersen published an article for the American Journal of Diseases of Children: “Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: A Clinical and Pathological Study.” In it, she described nearly 50 cases of patients diagnosed with celiac disease who showed the hallmark signs of what we now know to be cystic fibrosis.

Andersen’s publication was well received and began a broader dialogue around the new disease. Concerned parents traveled from across the country to seek her counsel, and her work unexpectedly shifted from pathologist to pediatrician as families poured in to see her at Columbia. Soon she had amassed a catalog of photos, delivered by hand and by mail from grateful families, featuring the smiling faces of the young patients she had diagnosed. In the years that followed, she would become the founding physician, leading expert, and de facto matriarch of cystic fibrosis.

The Gold Standard

When Paul di Sant’Agnese, MD, joined Andersen at Babies Hospital in 1943, he began treating CF patients with penicillin after petitioning to use the rationed drug. He stood in line for hours, holding notes on patients to justify his request, and was able to get several vials of the drug. Penicillin had profound effects on the children’s abilities to fight infection and extended their lives. When the penicillin supply became more plentiful, Andersen and di Sant’Agnese included it in the CF treatment regimen.

Doctor holding a medical device
Paul di Sant’Agnese

In the late 1940s, di Sant’Agnese contributed another landmark discovery in the history of CF. When a heat wave tore through New York City in 1948, he found several of his CF patients among children being treated for heatstroke. Their small hands left salty white impressions on water glasses. After some of the same CF patients returned with heatstroke symptoms the next year, di Sant’Agnese started investigating sweat physiology.

Within a few years, di Sant’Agnese began using a sweat test on four teens, two with CF and two without. He replicated the experiment in 43 more children before sharing findings with colleagues that children with CF produced sweat with dramatically higher levels of sodium, chloride, and potassium. He suggested that this could be a safe, reliable way for diagnosing the disease in early childhood, and as others built on his work, physicians embraced the sweat test for being fast, accurate, and painless. di Sant’Agnese’s sweat test remains the gold standard for CF testing today, and the Paul di Sant’Agnese Distinguished Scientific Achievement Award is the highest scientific honor awarded by the Cystic Fibrosis Foundation.

The Fundraiser

Wynne “Didi” Sharples was a 1951 graduate of what is now the Vagelos College of Physicians and Surgeons. As a pediatrician and mother of two children with CF, Sharples was instrumental in bringing attention and funding to the cause.

The daughter of a wealthy industrialist, Sharples was well connected and well positioned to make an impact on the disease. “Breath from Salt” author Bijal P. Trivedi describes Sharples as “a socialite with the means, connections, visibility, and time to dedicate to the cause” and “a powerful ally in the fight to treat the disease. With two sick children of her own, Sharples understood the urgency of finding the cause and cure.”

Doctor examining a young child
Dr. Herbert Cohen examines a young cystic fibrosis patient. This photograph was taken for a story done on CF that appeared in the October 1965 issue of Stethoscope.

Sharples launched the National Cystic Fibrosis Research Foundation in 1955, with chapters in New York, Los Angeles, Philadelphia, Hartford, and Boston. She recruited other parents (many of whom were already leading smaller but similar efforts) and physicians to create one formidable organization that quickly evolved beyond its grassroots origins.

Andersen and di Sant’Agnese served on the foundation’s medical education committee and helped inform its early CF education efforts, including informational booklets, a quarterly newsletter, and articles in national magazines and newspapers.

By the late 1950s, the foundation had brought considerable attention to the disease, and its efforts were gaining traction. A New York Times article announced the foundation’s “War on Cystic Fibrosis” in 1957, describing the disease and the early efforts to test and treat it.

While Sharples’ leadership had been effective, her uncompromising approach created division. To her, research was the foundation’s clear No. 1 priority, and she argued that the foundation overspent on administration and publicity. She resigned in 1959 but left the foundation primed to succeed. The original five chapters had grown to 70, fundraising efforts were advancing, and the foundation was well regarded and had close allies in Congress and the NIH.

The foundation Sharples helped launch went on to become the Cystic Fibrosis Foundation, a leading non-profit for CF and a major contributor to research.

The Future of Cystic Fibrosis

Though their contributions to CF were great, Andersen, di Sant’Agnese, and Sharples all shared the frustration of being pioneers in the early days of a new disease. But today, 86 years since Andersen identified cystic fibrosis during a routine autopsy in the basement of Babies Hospital, the outlook for the disease is dramatically different because of their early efforts.

What was once a childhood death sentence has become a manageable (albeit still incurable) disease, with most patients surviving well into adulthood. Today, the average life expectancy of a cystic fibrosis patient born between 2015 and 2019 is 46 years.

Emily DiMango, MD, serves as director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University Irving Medical Center. With a grant from the Boomer Esiason Foundation, the program has become the premier site for adult cystic fibrosis care and research in the New York metropolitan area and one of the busiest clinical trial sites in the United States.

“The last year and a half has seen probably the biggest advance in CF in decades. We have gone from taking care of patients who coughed all day, who had to be absent from school and work during frequent infections, to people now telling us they feel like their disease is cured.”

The program was involved in the clinical trials that led to the approval of Trikafta, the first triple combination therapy available to treat patients who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation is estimated to occur in 90% of CF cases.

“The last year and a half has seen probably the biggest advance in CF in decades. We have gone from taking care of patients who coughed all day, who had to be absent from school and work during frequent infections, to people now telling us they feel like their disease is cured.”

While the new therapy does not cure CF, it regulates the patient’s salt imbalance and effectively curbs symptoms. “It’s too soon to know how it will affect survival. But we know that it improves lung function very significantly and slows down the progression of lung disease,” says DiMango. “We’re very hopeful that with the introduction of this drug, we’re going to see great strides in survival for people with CF.”

Reflecting on the legacy of Andersen and others, DiMango and colleagues acknowledge their early contributions. “It’s hard to wrap your head around what it must have been like for Dorothy Andersen,” says DiMango. “Just being a female physician then was pretty remarkable, not to mention her contributions to CF. We’re all very grateful for her contributions and for what others have done to save so many lives.”

Like Andersen before her, DiMango has amassed a collection of photographs featuring smiling children and their families. Where Andersen’s collection of photos featured children newly diagnosed with CF, DiMango’s are of another group entirely. They are the children of her CF patients, who have not only survived beyond childhood, but grown, flourished, and started families of their own.

“This entire bulletin board behind me is filled with photos of babies of my CF patients. When I started 20 years ago, it was a big deal for an adult with CF to have a baby. Over the last 20 years, we’ve had around 50 babies born to patients in our practice,” she says.

“I have even more pictures waiting to go up now, a whole pile. I’ve run out of bulletin board, and that gives us a lot of hope.”

References

More information

This article was originally published in the Fall/Winter 2021 issue of Columbia Medicine magazine.

For the full story of Andersen, di Sant’Agnese, Sharples, and countless others who advanced the cause of cystic fibrosis, read “Breath from Salt” by journalist Bijal P. Trivedi.

John Scott Baird, MD, associate professor of pediatrics and a 1985 VP&S graduate, wrote a biography of Dorothy Andersen, “Dorothy Hansine Andersen: The Life and Times of the Pioneering Physician-Scientist Who Identified Cystic Fibrosis.” It was published in November 2021.

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