Stories of Life

which rise and fall, and sometimes rise again, with chemistry

Wow, it’s been a month, huh? Once again, I’ve collected an assortment of tidbits the universe sent my way since the last post and turned them into… something? So here’s what happened as we hurtled into the school year, just trying not to burn up on re-entry.

Two weeks in, we had Parents’ Nights at the kids’ schools. We were led through a typical day in the lives of our students—10 minutes in each class, shuffling awkwardly through crowded halls at the bell. Our sixth-grade son’s science teacher asked us to write down what learning style we thought worked best for our kids. I wrote, on behalf of the kid whose nose is always in a fantasy book, “storytelling and mystery”.

Our eighth-grader’s science class, we were told, would be structured into two main sections: life science, including genetics and evolution, and physical science, including physics and chemistry. Now, I know it’s not the teacher’s job—nor should it under any circumstances be mine—to write the curriculum. Outwardly, I smiled and nodded, because even though teachers are increasingly younger than me, the teacher-pleaser inside me still thinks we are eight years old. But the clamouring inside my head sounded like this: What?!? Life science IS chemistry! They are NOT in separate categories!¹

The next week, I came across the following passage in the book Trespassing on Einstein’s Lawn by Amanda Gefter, who regular readers will remember as the writer who recently unearthed the work of the nearly forgotten Peter Putnam. The book hilariously describes how her passion for physics (despite never formally studying it) led her to pose as a science journalist until she became a real one. After describing how the compass Einstein’s father gave him when he was four years old ignited his curiosity about unseen forces in Nature, she wrote this:

My father, too, had offered me my first clue that reality is not what it seems. Only in my case the clue wasn’t an object but an idea, and instead of turning out to be Einstein I grew up to be a counterfeit journalist with more questions than answers. Still, it occurred to me now that the best gift a parent can give a child is a mystery.

And then later, at work, an encouraging article in Endpoints News grabbed my attention: “Regeneron heads to FDA with treatment for very rare bone disease”. The disease is called fibrodysplasia ossificans progressiva (FOP), and for these patients, their muscles, tendons, and ligaments are slowly replaced by bone.

The story that follows actually took place over a few conversations, but this is basically how it happened. Like many kids, our 11-year-old went through a Harry Potter phase, reading every book, waving wands, and putting spells on us. So when I asked him if there was a spell for turning people to bone, he thought for a few seconds and said, “Petrificus totalis.”

I asked him and his 13-year-old brother to imagine that happening in real life, with no spells to reverse it. They let that sink in. As usual, they had questions. “At what age does this happen? Is it only older people? And, do the nerves turn to bone too, so they don’t feel the pain?” I had to tell them that it can start at ages younger than theirs, and no, sadly, it’s very painful. The 13-year-old made a sound like he’d been punched in the gut. I hadn’t even told them that patients’ ribcages become so rigid that most die of cardiorespiratory failure by their 50s.

While I painted this watercolor, I spent my own time thinking about these patients who become trapped in their own bodies as their muscles turn to sheets of bone, like this.

Then, I told them the good news about the new medicine, dropping it in that the scientists had to figure out how it was happening first. And then the magic happened. They said, “Wait, how is it happening??” I had them.

I told them about the network of proteins in their bodies that pass a message from one to the next, chemically whispering, “Make more bone. Pass it on.” There is also a protein in the network that whispers “Stop making bone” when the body doesn’t need it. But for patients with FOP, the recipient of this cease-and-desist message has a specific mutation that makes the message sound instead like “Make more bone.” It passes the wrong message on, like the breakdown in a game of telephone.

Scientists at Regeneron Pharmaceuticals pinpointed this mechanism² and then found a way to fix it,³ ultimately creating a medicine that keeps the misunderstood protein away from the mutated one. It worked so well that the clinical trial’s independent monitoring board recommended that they start giving it to the placebo group. It would be cruel not to.

I asked the kids how we could tell the story as a mystery, and they had an idea for a novel written from the perspective of a kid with FOP who was starting to feel symptoms, but his parents had decided not to tell him the truth. Ignoring for the moment how easily they were able to evoke these gaslighting parents, I asked them to go on. So the kid, who is not a scientist, has to find a way to solve the mystery before it’s too late.

That reminded me of David Fajgenbaum’s memoir, Chasing My Cure: A Doctor’s Race to Turn Hope into Action. It is the true story of a medical student and former Georgetown quarterback who came down with a mysterious disease, then raced to figure out how to treat it in between (and sometimes during) five near-death experiences over the course of years.

It also reminded me of Sonia Vallabh and her husband Eric Minikel, who left promising careers in law and urban planning, respectively, after Sonia lost her mother to prion disease in 2010 following a rapid decline that started at age 51. Sonia learned that she had the same DNA mutation in her prion protein gene, making it all but certain that she would suffer the same end—a hideous dementia followed closely by death. Fifteen years, two Ph.D.s, and at least one promising drug candidate later, they are witnessing what few scientists ever get to—the therapy they developed is currently being tested in clinical trials.

So on the eve of the announcement of the Nobel Prize in Chemistry, let me point out that science is full of stories like these, and stories like these are full of chemistry. The bone formation that becomes uncontrolled in FOP involves a change in states of matter from ions in solution to the solid crystal lattice of hydroxyapatite, made up of both ionic and covalent bonds in dizzying symmetries. David Fajgenbaum discovered (Spoiler Alert) an overabundance of a protein in his blood for which there was already an FDA-approved chemical that blocks it. That chemical (rapamycin) is still saving his life 11 years later. Sonia Vallabh’s mutation causes a protein to fold incorrectly, exposing amino acids whose chemical properties lead to its aggregation in the brain. As humans, we are wired for storytelling, maybe none so more than kids. And there are so many mysteries in medicine remaining for them to solve.

“So is this a mommy blog now?” you may be asking. I don’t think so (I would have called it Signs of a Struggle), but that’s not for me to say. What I do know is that how kids learn science is everybody’s problem. Because how the next generation thinks about science as they approach voting age affects us all.

1. Not one to dig into curriculum, I found myself later reading about how Massachusetts recently adopted a more “inquiry-based” approach to teaching science in its public schools instead of rote memorization, so that’s great.

2. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sarah J. Hatsell, Vincent Idone, Dana M. Alessi Wolken, Lily Huang, Hyon J. Kim, Lili Wang, Xialing Wen, Kalyan C. Nannuru, Johanna Jimenez, Liqin Xie, Nanditha Das, Genevieve Makhoul, Rostislav Chernomorsky, David D’Ambrosio, Richard A. Corpina, Christopher J. Schoenherr, Kieran Feeley, Paul B. Yu, George D. Yancopoulos, Andrew J. Murphy, Aris N. Economides. Sci Transl Med. 2015; 7(303):303ra137.

3. How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva Dushyanth Srinivasan, Martin Arostegui, Erich J Goebel, Kaitlin N Hart, Senem Aykul, John B Lees-Shepard, Vincent Idone, Sarah J Hatsell, Aris N Economides^. Biomolecules, 2024; 14(1):101.