Preprint Biological Insights from Genome-Wide Association Studies and Whole Genome Sequencing of [ME/CFS], 2026, Maccallini et al

[AliceLily]

I remember in my sickest years lying in bed trying to get through every day, year after year, no internet. I felt so alone and so scary ill. I longed for research. S4ME would have been a great help knowing things were being done and members here were constantly looking into it. Thank you everyone, means so much to me.

 

[Sasha]

Only this week we have woken up to the fact that ME/CFS gives an unusual response to buspirone. I have already asked some colleagues if they would like to look at that again. The genetic stuff is falling in to place in a way that I suspect can only snowball. [...] the rest of us think we might just have turned the biggest corner for twenty years.

With the buspirone reaction? Or lots of things together?

 

[Jonathan Edwards]

Or lots of things together?

Lots of things.

 

[duncan]

That's a giddy refrain. I feel better.

 

[TamaraRC]

I'm going to sign off for my night, but set up a discussion thread on the evidence for disruption of phospholipids if you want @mariovitali and I'll catch up tomorrow. Or, I can make a thread tomorrow.

@mariovitali I have started a new thread to continue discussion about disruption of phospholipids.

 

[ScoutB]

You only need one lot of people and there is a big lot here.

I've been thinking about this, in light of all the exciting new ideas people shared this week. It's amazing how much progress you can make with a group of clever, motivated people working together.

E.g. contrary to the popular image, mathematicians are extremely sociable (well, about math at least) and constantly get together at conferences and online because it accelerates problem-solving so much (and it's more fun).

Somehow during undergrad I never realized how similar problem solving in biology can be to problem solving in math. E.g. in both cases it's key to have a grab-bag of common counterexamples to test new ideas against. In math these are things like weird functions (also, funnily enough, the number '2'). In biology, better-understood illnesses seem to play the same role?

Recently, AI solved a non-trivial open math problem, and a bunch of famous mathematicians got together to write a mildly fascinating paper on the state of things and their feelings about it.

A lot of it feels relevant to us. E.g. here's Daniel Litt explaining how this math problem (which, it turned out, we had the tools to solve) remained unsolved for so long:

One possible explanation for such low-hanging fruit: those working on the problem have anchored onto a non-optimal approach or belief about the truth. Another: the solution requires ideas from areas with which most of those working on the problem are unfamiliar.

In my own area—algebraic and arithmetic geometry—there are simply very few practitioners, and so arguably all problems are attention-bottlenecked.

I love the term "attention-bottlenecked" and I feel like this forum fights against exactly the three issues he outlined.

 

[Utsikt]

I've been thinking about this, in light of all the exciting new ideas people shared this week. It's amazing how much progress you can make with a group of clever, motivated people working together.

E.g. contrary to the popular image, mathematicians are extremely sociable (well, about math at least) and constantly get together at conferences and online because it accelerates problem-solving so much (and it's more fun).

Somehow during undergrad I never realized how similar problem solving in biology can be to problem solving in math. E.g. in both cases it's key to have a grab-bag of common counterexamples to test new ideas against. In math these are things like weird functions (also, funnily enough, the number '2'). In biology, better-understood illnesses seem to play the same role?

Recently, AI solved a non-trivial open math problem, and a bunch of famous mathematicians got together to write a mildly fascinating paper on the state of things and their feelings about it.

A lot of it feels relevant to us. E.g. here's Daniel Litt explaining how this math problem (which, it turned out, we had the tools to solve) remained unsolved for so long:

I love the term "attention-bottlenecked" and I feel like this forum fights against exactly the three issues he outlined.

I was about to post something about that paper. I agree with your analysis of the situation here.

We just have to try our best to not quash the new ideas too quickly if they are packaged in a way or with other things that are easy to pick apart (note to self). It might still be that the principles or angles take us further.

In a way, we have to manage to be very stubborn about following a particular argument to the very end, but also very open to new ideas. It gets disorienting fast.

 

[V.R.T.]

We just have to try our best to not quash the new ideas too quickly if they are packaged in a way or with other things that are easy to pick apart (note to self). It might still be that the principles or angles take us further.

I do wonder if there are any long covid (or MECFS) papers that we have dismissed on the basis of describing unusual cytokine activity as 'inflammation' or talking about 'T cell exhaustion' or whatever that might be telling us something important underneath the usual memes.

 

[Utsikt]

I do wonder if there are any long covid (or MECFS) papers that we have dismissed on the basis of describing unusual cytokine activity as 'inflammation' or talking about 'T cell exhaustion' or whatever that might be telling us something important underneath the usual memes.

If so they did a good job at hiding it.. Hopefully it will show up in literature searches if the same things are talked about elsewhere.