Why mechanisms matter

I think that every academic has had the dispiriting experience of writing what they thought was a good paper, only to have great difficulty publishing it. This post is about one of these – which has been hanging about in my “do something with this, someday” file for four years or so.

It was a paper about Whipple disease, and it was co-written with a group of UCL medical students. Going back to look at it again now, I think that I can see what the journal editors saw – it’s a very interesting case, but it’s a pretty boring paper, largely because it turns on lots of tiny technical details which are required to tell the story properly. That’s a shame, because the guts of the case have news value (as they say) for researchers interested in the role of mechanisms in the health sciences.

Whipple disease is a really rare infectious disease that was first described in 1907 by George Hoyt Whipple , who was later to win a share of the 1934 Nobel prize in medicine for his work on anaemia.

The disease was first described from a single case. At the time, Whipple made two very different suggestions regarding its aetiological mechanism. These were that either:

  1. the disease was caused by an infectious agent, or
  2. that it was caused by a metabolic problem of some kind

We now think that 1. is roughly right (a causal bacterium was found in 1961 and named as Tropheryma whipplei in either late 1991 or early 1992, depending on who you listen to). However, this wasn’t always the case – in fact, for about the first forty years or so after Whipple’s original description, the metabolic theory was preferred. Note, though, that Whipple’s evidence for the two distinct aetiological mechanisms was pretty weak, with little to recommend one over the other.

What interests me is that the choice of one of the two suggested disease mechanisms really had a profound effect on shaping the programme of research on Whipple disease as a whole – so it was largely performed by researchers interested in metabolic diseases, analogies were drawn with other metabolic diseases, and many questions (that, it turned out, were terribly important ones) were ignored. This is dealt with at some length in the paper, so if you’re interested, I’ll leave you to read that (on Philpapers), but one interesting demonstration of the strength with which the metabolic mechanism was held was that, even in cases where Whipple disease was successfully treated with antibiotics, researchers still believed that the disease was not caused by an infection (as discussed in a more recent review).

In short, mechanisms matter because an initial suggestion as to the nature of a mechanism (even if this suggestion is not particularly well-evidenced) may determine a research agenda over the long-term.

I’ve posted the whole think on Philpapers, so you can have a look if you’d like.


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