Monday, August 2, 2010

I am the Norge Repairman of the primary literature

In one of those strange coincidences of the blogosphere, Chad (at Uncertain Principles) and Janet (at Adventures in Science - now in her new digs are Scientopia) are discussing the role of the primary literature in the sciences, at exactly the same time as I was plumbing the depths of the primary literature.

See, for the past few weeks I myself have been conducting an extensive expedition through the literature on the M current. M current stands for muscarinic current, which is a potassium current in various neurons that is closed by muscarinic agonists (among others). This reduction leads to enhanced neuronal excitability and more action potentials. The current has been most widely studied in sympathetic neurons, which do something to pumps or plumbing or something. Go ask her.

This sort of detailed review is something I’ve been meaning to do for some time, but never forced myself to start. But the life-work balance has been recalibrated recently (hence the increased posting here - more on that later?), so I’ve finally begun. I’ve been tracing back through the literature and cited references, checking reviews, and also reading what I can find about the scientists who contributed to the field. I find this a great way to engage in the literature, because tracing the development of the ideas helps .e put them in a context that I find much easier to remember. I’d hazard a guess that this would be a lot more useful to undergraduates engaged in research, than simply throwing the “primary source” of a bunch of ganglia at them while telling them to “do research.”

I find the M current story compelling for a couple reasons. The first relates to why studying the primary literature can be an important part of doing science. The excitation resulting from muscarinic stimulation was obvserved as far back as the early 1950s, yet it wasn’t until the mid 2000s that a pretty complete picture of the entire process, including receptor proteins, ion channels, signalling molecules, was developed. And in that time, as you might imagine, there were a lot of missteps, and numerous errors. That lesson, that wrong things get published all the time, is a crucial lesson. Another lesson is that science doesn’t develop as a neat and tidy, linear march to more and more understanding. Both of these are rarely discussed in science textbooks. he only counterexamples I can come up with are Newtonian versus quantum mechanics, and Lamarck’s theory of evolution). Most of the rest of science in textbooks is so boring. Message to undergrads: Science can be a whole lot more fun than that.

The second reason is that the 55 odd year trip from initial observation to final signalling molecules gives me hope on my own research topic. In my day job I’m studying how G protein coupled receptors activate a particular transient receptor potential (TRP) channel, TRPC5. But it’s been a bear, because we’ve exhausted the usual suspects, and haven’t yet nailed down the culprit. (Also, the channel is just a pain in the f***ing ass, clearly being a devotee of Marquis de Sade.) In fact, it’s entirely possible that we’re on the wrong path entirely (I said “possible”. Not “likely”). Still, seeing as this channel was only cloned in 1996, and “real” recordings of its activity date from 1999-2000, I figure we still have some time to go before making a run at the title of “Longest duration from ion channel to signalling pathway elucidation.”

I plan to do some blogging on the seminal papers of the field, as well as the its overall development.


Namnezia said...

Good luck with that! It's always fun to read everything about a new topic. For the M-current, I'd start with Hille's book and read all the references for context. When I was a postdoc I spent a some months reading about sodium-sensitive potassium currents, which I thought I had found in the cells I was recording from. Unfortunately the whole thing turned out to be an artifact of the way my recording software was set up. After a few days spent drinking tequila, I recovered and moved on. So good luck!

Anonymous said...

You rock. M current rocks. I had a WHOLE LOT of M current in grad school courses because it illustrates the principles of scientific discovery, as you said. So apparently there is a training program out there that completely agrees with you...

Nat Blair said...

Namnezia - Hille's 2nd edition has very little on the M current actually, perhaps because he only started studying it sometime close to that point. Not sure what the 3rd edition has, but frankly I don't like that version. And for right now, I'm consciously avoiding reviews on M current. I want to get a handle on the primary experiments first.

Heh, I too spent some time thinking about Na+ activated K-current in grad school. I could never shake the feeling that it was simply a result of poor Rs compensation and inadequate voltage clamp. After lodging that bias in my brain, I haven't really engaged with the story of cloning it.

@Anony - Thanks! M current does indeed rock. The more I think about it, the more the story illustrates so many aspects of research progress, and it's nice to know other people get that sense too. It will be interesting to follow through.