Thread by @kellybclancy

It's a great honor to share this piece I wrote for @WIRED about two beautiful humans, Sonia Vallabh and Eric Minikel (@cureffi). They’re a married couple using science to save Sonia’s life--you can read all about their amazing quest in the article. wired.com/story/sleep-no…

If you’re looking to fund a worthy cause, consider donating: prionalliance.org If you're a philanthropist, consider how modest funding for their work will change the regulatory space for neurodegenerative disease, and pave the way for others like Alzheimer’s & Parkinson’s!

There’s loads I didn’t get to cover in this piece, but I would like to take a little time to discuss how talking to them has changed me as a scientist.
Before that, I have to thank my amazing editor, @anthonylydgate, and the fact checking team, and the whole crew at Wired.

It was a joy to work on this, and they made this piece 1000% better than I could have on my own. I can’t stress enough how much writing benefits from being a collaborative effort, and I feel lucky to have worked with so many geniuses.

I’m a basic research scientist, the closest I get to ‘the clinic’ is thinking about how my work might one day, in twenty years, translate into something that could help patients. The clinical work is someone else’s job, I figure.

It’s easy to cynically sell one’s work to grant agencies as ‘relevant to condition x, y, z’ without giving much thought to what would need to happen for it to actually get there. I suspect a lot of basic scientists think of this as someone else’s problem.

I often read papers with clever toy solutions to mouse models of diseases, but I don’t think I’ve ever realized just how great a divide lies between these ‘quasi-therapeutics’ and real, clinically-viable therapeutics.

I had never given real thought to just *how* stringent and prescribed the regulatory space is. Say you’ve developed a compound that really works to lower x in disease y: how can you show it’s effective in a traditional clinical trial?

How could you actually recruit patients? Many diseases are rare (though, 1/10 people have a rare disease! “Rare diseases” are not so rare...), or have a wildly variable onset, and so are intractable to study with traditional clinical trial structures.

It’s amazing if you came up with a novel solution. Is it something we could ever hope to ACTUALLY implement it in patients, is it something that could ever be amenable to clinical trials, given the regulatory space, in our lifetime?

Maybe you’ll invent something so revolutionary the regulatory space will shift to allow it. But it’s problematic that scientific funding works to incentivize novelty.

Existing therapeutics that might have applications in any number of diseases languish on the shelf because we’re busy inventing new cures. Novelty is important. So is using stuff that we already know works. Sonia and Eric are repurposing a therapy that’s been around for 20 years.

It’s hard to fund research on that, there’s no novelty there, except in the application. But patients don’t want novelty, they want something safe. NASA still uses technology from the 60’s in its shuttles--because it’s dependable, and we know exactly how it works.

Who is working to employ all the wonderful therapeutics we already have in patient populations? No doubt there are many things that might work off the shelf, but who is following up on these?

Many scientists I spoke to held Sonia up as evidence of the importance of the patient scientist. I think this is the wrong lesson. Sonia is extraordinary, but we can’t expect patients and advocacy groups to cure their own disease. They already bear the burden of their disease.

I might sound overly conservative--I concede we need blue skies ideas! We also need to make the most of all the brilliant work that’s already been done.

Maybe we could all try to think a little more like patients researching their own disease. Sonia and Eric are people doing great science, because they have no other choice. There’s no point p-hacking results, they care zero for publications. All they care about is finding a cure

(It’s untrue to say they care zero. Scientists work within a hierarchy of imperfect optimizations, shorthands for quality that leaves a therapeutic like this, with real genuine promise, unfunded. They need to play the game, to some extent, to get grants and papers.)

We need more mechanisms for connecting patients with basic researchers. More researchers that have a basic familiarity with the clinical regulatory space (I thought I had some, but was totally mistaken!). Above all, we need to make more use of what we already have.

Most scientists are aware of how problematic the incentive structures in research are. Would love to hear anyone’s ideas for how we fix this.