Call the Midwife Evokes Cystic Fibrosis in a Simpler Time

VN:F [1.9.22_1171]
Rating: +8 (from 10 votes)
Children with cystic fibrosis too young to pronounce the disease's name call it 65 Roses.

Children with cystic fibrosis too young to pronounce the disease’s name call it 65 Roses.

Previous posts bashing SyFy’s Helix and Dan Brown’s Inferno might suggest that I’m hypercritical of TV and films. Happily, the third season premiere of BBC’s excellent Call the Midwife shows that it is indeed possible to get the science right while telling a compelling story, without special effects and nonsensical intrigue.

A CLASSIC CASE
On the March 30th episode, a young mother was distraught. Her month-old baby had stopped gaining weight and then started losing it, was fussy and clearly suffering from abdominal pain. He was filling nappies with foul-smelling loose stools so fast that even the father had to help, something unheard of circa 1959 in the poor, working class neighborhood of London’s East End where the series is set.

Nurse/midwife Jenny Lee (Jessica Raine) narrates in flashback the memoirs of the late Jennifer Worth. Not as slick as Downton Abbey, the show presents a glimpse of time that is just as addicting. Nurse Jenny, a 22-year-old of privilege when she arrived at Nonnatus House in 1957, expected to be working at a small private hospital, but instead had to adjust to life in a convent, where the nurse-midwives lived.

The third season opener was a trip back to a time when we didn’t test for dozens of the 1600 mutations known to cause cystic fibrosis (CF), let alone sequence exomes or genomes to get to difficult diagnoses. Instead, observation ruled. And the program did it spectacularly.

Clubbing of fingers reflects poor circulation.

Clubbing of fingers reflects poor circulation.

Many viewers probably recognized the classic signs of CF, but the nurse/midwives, nuns, and lone doctor didn’t. Abdominal pain. Recurrent infections and fevers. Both baby Ian and his toddler brother Martin choked on phlegm. And everyone was deeply puzzled.

Early on, the young father told nurse Jenny that his brother died at age 4, and no one ever knew why. His two young sons were bringing back terrible memories. With the father’s family history quickly uttered, the pieces fell into place, at least in hindsight.

It was astute Sister Monica Joan, whom everyone dismissed as well on the road to dementia, who noted the salty taste to Ian’s brow, ran upstairs to the books that she spent her days meticulously cataloging, and came back down. With a sly smile, she uttered the very quote “from Queen Anne’s time” that is in my and every other genetics textbook:

Woe to that child which when kissed on the forehead tastes salty. He is bewitched and soon must die.

No one paid attention to the silly saying from the 1600s. The young mother blamed herself, as did the male doctor. Perhaps the mother’s depression was making her neglectful, the good doctor, resting and enjoying a smoke, asked as Nurse Jenny exhausted herself thumping on the chest of the baby to free him from the stifling mucus.

Heart-and-lungsA little while later, frustrated at being ignored, the batty old nun braved a rainstorm to thrust the book into the hands of the doubting doc. He finally read it and the light bulb went off. The boys had CF.

ASSEMBLING THE PUZZLE PIECES
Here’s a description of CF from my human genetics textbook (new edition coming in the fall, shameless book plug):

“Physicians first described the condition in medical journals in 1938 as a defect in channels leading from certain glands, causing extremely thick mucus and resulting in infections in the lungs; a clogged pancreas, preventing digestive juices from reaching the intestines; and salty sweat. Children with CF, with their slow growth and frequent infections, are sometimes first diagnosed simply as suffering from ‘failure to thrive.’”

The history of recognizing CF goes back farther. The saying that the nun quoted comes from the German Children’s Songs and Games of Switzerland, and evokes an observation by a Spanish professor of medicine from the early 1600s equating salty skin with being bewitched.

Then in the early 1900s, several physicians noted that oily smelly stools, cough, and death in early childhood often went together. Dr. Dorothy Andersen at Babies’ Hospital of New York published the 1938 paper naming the disease, which describes the problems in the lungs and pancreas.

512px-CFTR_Protein_Panels.svgIn 1953 came the “sweat test,” after a heat wave in New York City filled emergency rooms with kids who had CF. They were the first to dehydrate and suffer from heat exhaustion. In 1989, Drs. Lap-Chee Tsui, Francis Collins, and their colleagues reported discovery of the gene and its encoded protein, the cystic fibrosis transmembrane regulator (CFTR).

A TRUE STORY
The Call the Midwife episode was a true story, that of English actress Jenny Agutter, who plays Sister Julienne. She told writer Heidi Thomas about her own family history.

Agutter lost an older brother Christopher to “unexplained stomach problems,” and remembers, at age 6, looking forward to the homecoming of her new sister Bridget. The baby never left the hospital, and Agutter’s mother never quite recovered from her grief, not understanding that it wasn’t her fault.

In 1980, Agutter’s niece Rachel, daughter of her brother Jonathon, whose childhood was exactly like that of Christopher and the two boys in the episode, was diagnosed. Jenny was tested at age 37 when pregnant and found to be a carrier, but fortunately her husband was not.

THE EVOLUTION OF TREATMENT
The episode ended with the doctor reassuring the parents that things could be done to help their sons. Today’s median life expectancy, the early 40s, is way up from age 5 back in 1938, but not good enough.

Strategies to treat CF have grown more targeted as probing the 1600+ ways that CFTR ion channels misform and misfold has revealed vulnerabilities. Treatments range from classic postural drainage and enzymes sprinkled on food, to antibiotics and anti-inflammatories to prevent and quell infection, to nuclease-based Pulmozyme to break up the sticky mucus. Pulmozyme was the first drug approved solely to treat CF, in 1993.

200px-Fart.svgVibrating vests treat the phenotype; gene therapy has yet to help the genotype, although a drug on the horizon, Ataluren, can shield the nonsense mutations that account for a small percentage of patients, enabling synthesis of functional CFTR protein. One new drug restores the liquid on airway surfaces, and the protein-refolding blockbuster drug Kalydeco refolds the errant chloride channel protein so that it can make its way to the cell membrane, where it establishes the ion flow that keeps secretions moist. Patient chatter on Kalydeco websites reports improvements from amazing strides in lung function to noticeably less stinky farts.

Here’s a pipeline of what’s coming in CF treatment.

But new problems arise. One is multidrug-resistant Mycobacterium abscessus, which is infecting the lungs of up to 10 percent of CF patients in the US and UK. And that may be the tip of an iceberg. Sequencing lung fluid from patients identifies bacterial genomes that we didn’t even know lurk in the lungs ravaged by the disease.

(Dept. of Energy)

(Dept. of Energy)

RICKI’S RANT
I loved the episode of Call the Midwife for almost as many reasons as I hated the scientifically illiterate, testosterone-infused Helix and Inferno. The science was accurate, both in historical context and in hindsight. The daily hands-on nurse knew far more than the distant doctor. A woman thought to be demented had a clear memory when it mattered, and noticed a sign of disease that others had missed. And in that little pocket of London poverty decades ago, the women were in charge.

Call the Midwife is a rare gem.

VN:F [1.9.22_1171]
Rating: +8 (from 10 votes)

Creative Commons License
Call the Midwife Evokes Cystic Fibrosis in a Simpler Time by DNA Science Blog, unless otherwise expressly stated, is licensed under a Creative Commons Attribution 3.0 Unported License.

This entry was posted in Uncategorized and tagged , . Bookmark the permalink.

2 Responses to Call the Midwife Evokes Cystic Fibrosis in a Simpler Time

  1. Pingback: Call the Midwife Evokes Cystic Fibrosis in a Simpler Time | Today Health Channel

  2. Diane Witt says:

    I love PBS, therefore, most every special as well. Call the midwife, is one of my favorites. Thank you for this article.

    VA:F [1.9.22_1171]
    Rating: +1 (from 1 vote)