How Science Works: New Thinking about Neurodegeneration

The 511

I’m introducing a new category for my blog today — the 511. Back in the 20th century, we called 411 for information. Today, information’s aplenty, so you’re looking for something more. The 511 includes: 

  • 5 short paragraphs about medtech, biotech, or another science-y thing
  • 1 sentence for reflection (and maybe a laugh), and 
  • 1 track I’ve currently got in heavy rotation.

What’s the Story?

“Neurodegenerative diseases do not exist,” writes Alberto Espay, MD, MSc, with Benjamin Stecher. “All [these diseases] are labels neurologists created before we had the insight and tools needed to accurately define them.”

In Brain Fables: The Hidden Histories of Neurodegenerative Diseases and a Blueprint to Conquer Them (Cambridge, 2020), Espay and Stecher — a Parkinson’s disease (PD) expert and a PD patient and advocate, respectively — offer us another stark reminder of science as a paradigm-based inquiry. And now they’re advocating for a paradigmatic shift to translational medicine, or precision-based medicine, for PD, Huntington’s disease, and Alzheimer’s disease, for starters.

Hold Up. Wait a Minute. 

Thanks to the oath-inspiring Hippocrates (460-370 BC), abnormal cell growth and its spread to other parts of the body was labeled “cancer.” Had Hippocrates grown up in Iowa, say, he might have drawn naming inspiration from a spider, rather than an ocean-dwelling creature. Put another way: cancer didn’t name itself. Humans use labels in the form of taxonomies and disease pathologies and, ideally, especially in the sciences, test the continued utility of labels and their metrics with the advent of better diagnostic tools. In Brain Fables, Stecher reminds us how these representations — or fictions, a la Yuval Harari (Sapiens) — may allow us to cooperate with large numbers of strangers, but also endure despite their profound limits. The regard of PD as a disease rather than syndrome has real effects in terms of research grants and treatment. 

Okay: Lots of Moving Parts. How About Two? 

  1. Lewy bodies contribute to neuronal death in the brain (Parkinson’s). 
  2. Beta-amyloid plaque accumulation leads to neurodegeneration (Alzheimer’s). 

Good. How’s the Data Line Up? 

Well … 25% of folks who live past 90 years of age have Lewy bodies, but not PD. And many subjects with high concentrations of amyloid in the brain do not suffer from cognitive decline. Still, paradigms are stubborn things: Parkinson’s work is over 200 years old, hasn’t changed much, and we still have zero disease-modifying therapies. A new paradigm would begin by regarding Lewy bodies as symptoms — rather than the cause — of the disease. In AD, too, the NIH has called for a more vascular-centric paradigm of inquiry. 

Translational Medicine? Please Translate. 

Translational medicine is “an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside, and community.” Its key goals include the definition — and avoidance — of the typical hurdles, barriers and troubles in the pathway for taking scientific discovery into clinics. New paradigms would entail more flexibility, as well as a regard for the combinatorial impact of genetics and enviro-factors on a pathogenetic combination of mitochondrial dysfunction, neuroinflammation, cholesterol metabolism alterations, etc. (p. 59). (In today’s NYT, check out the stats on environmental toxins in this review of Ending Parkinson’s Disease.)  New technoscientific instruments can reveal more information about individual patients. In translational medicine, new treatments would prevail, the paradigms would be more precise, and human suffering would decline. All good things, yes?  

5(1)1 — On teamwork

“As far as our brains are concerned, if our social system rejects us, we could die. Given that our sense of danger is so natural and automatic, organizations have to do some pretty special things to overcome that natural trigger.” 

Amy Edmondson, Harvard U., in Daniel Coyle’s The Culture Code, p. 12  

51(1) — Music sample

Back in the day, my introduction to jazz came way of Miles Davis, moved through Charles Mingus, John Coltrane, and Art Ensemble of Chicago, but I always come back to reedman Eric Dolphy. For me, note for note, he played with a perfect balance of joy and pathos. And his phrasing on the bass clarinet? Oh, Nellie.

Here’s Dolphy’s “Jitterbug Waltz.” 

Charles Mingus on bass. Eric Dolphy on alto.

Thanks again for stopping by. If you like what you read, and you know someone else who might, too, please spread the word. 

I’m also on this thing called Twitter (@randaldoane). 

It’s probably just a passing fad. 

Sources 

Brain Fables (here)

https://www.frontiersin.org/articles/10.3389/fnins.2020.00256/full

https://www.medpagetoday.com/neurology/generalneurology/87645

https://www.ynharari.com/topic/power-and-imagination/

https://www.penguinrandomhouse.com/books/235200/the-culture-code-by-daniel-coyle/

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