Talk:David Colquhoun

Scientific career

The following is a large amount of material I have moved from the article. It needs to be reworked to make it more neutral and presentable in the article: Brangifer (talk) 04:59, 2 October 2011 (UTC)

In 1977 Colquhoun & Hawkes predicted that ion channel openings would be expected to occur in brief bursts rather than as single openings, and this prediction was verified in experiments with Bert Sakmann, in Göttingen and London (1981). This work led to the first solution of the classical pharmacological problem of measuring separately the affinity and efficacy of an agonist. In the context of ion channels, this problem is also known as the binding/gating problem. This problem remains unsolved for G protein-coupled receptors, because it was shown in 1987 that the classical methods for determining affinity and efficacy were based on a misapprehension.

The 1985 paper was later nominated as a “classic” by the The Journal of Physiology. In 1982 Colquhoun & Hawkes published a paper on the theory of bursts (and clusters of bursts) which gave a general expression for the distribution of the burst length (shown here on the design for a mug for those who attend a course designed to teach the mathematics needed for the equation).

Course mug design

It was clear that the burst length was what controlled the decay rate of synaptic currents, though the formal relationship was not derived until 1998.

Missed short events

Although the general theory of single channel behaviour was completed in 1982, it could not be used in practice for fitting mechanisms to data, because the recording apparatus is incapable of detecting events shorter than, at best, about 20 microseconds. The effect of missing short shuttings is to make openings appear to be longer than they really are (and likewise for shuttings). In order to use the method of maximum likelihood it was essential to derive the distribution of the length of what is actually seen, apparent open times and apparent shut times. Although the Laplace transform of these distributions was known, it was thought that they were not invertible until Hawkes and Jalali found an exact solution in 1990. The exact solution was a piecewise expression that got progressively more complicated as the length of the opening (or shutting) increased. The solution became usable in practice after Hawkes and Jalali discovered an elegant asymptotic solution in 1992. The application of the exact solution to joint and conditional distributions in 1996 opened the door to maximum likelihood fitting, which was implemented in a computer program, HJCFIT, which has been the basis of subsequent experimental work. The distributions of apparent open and shut times are often referred to as HJC distributions (for Hawkes, Jalali, Colquhoun).

Intermediate shut states

All the early work was based on mechanisms that were essentially generalisations of the simple scheme proposed by del Castillo & Katz in 1957, in which the receptor existed in only two conformations, open and shut. It was only when the glycine receptor was investigated that it was realised that it was possible to detect an intermediate shut state (dubbed the “flipped” conformation), between the resting conformation and the open state. Subsequently it was discovered that this extra “flipped” conformation was detectable too in the nicotinic acetylcholine receptor. Lape et al. (2008) found that partial agonists were partial, not, as had been supposed since 1957, because of a deficiency in the open reaction itself, but because of a deficiency at an earlier stage, a reluctance to move from the resting conformation to the intermediate shut state that precedes opening. The actual shut-open conformation change turned out to be much the same for partial agonists as it was for full agonists. In the original formulation the flipping reaction was supposed to be a concerted transition. The essentials of this new mechanism were confirmed by Mukhtasimova et al. (2009), who generalised it to be the case where the subunits can flip independently.

Editorial notes

I'm going to start making some copy edits and adding requests for references, etc.. We can always fix this and revert back to a previous version, so don't worry. -- Brangifer (talk) 19:24, 2 October 2011 (UTC)

We need a ref for "a classic". I added a URL and a more complete ref for the 2007 article. Can you find a ref for the "classic" comment? It would be nice to have URLs and more complete refs for everything else. -- Brangifer (talk) 19:29, 2 October 2011 (UTC)

Reference 6 is a "classical perspectives" paper, so is that not sufficient justification? — Preceding unsigned comment added by RBJ (talk • contribs) 20:22, 2 October 2011 (UTC)

I'm really not sure. I'm not familiar with the journal's practice and I'm not a professional scientist. The current wording is: "The 1985 paper was later nominated as a “classic”...". I suspect by slightly rewording that we'd be on safe ground. Right now, since the paper is authored by Colquohoun, it could be viewed as self-promotional language (and we can't have that), so please suggest some alternative wording that's more neutral. -- Brangifer (talk) 20:49, 2 October 2011 (UTC)

Okay! I've done some searching of the website and found a great ref to justify that wording. I'll add it in a moment. -- Brangifer (talk) 21:04, 2 October 2011 (UTC)

Done. -- Brangifer (talk) 21:09, 2 October 2011 (UTC)

Sorry about incomplete ref, Did you try looking at the paper? It's here http://jp.physoc.org/content/581/2/425.full.pdf+html?sid=07e4e6d3-5f15-4f7e-92c2-702eb2e1bd1d

It is headed "Classical Perspective" and starts with the words "The only problem about being asked to write a perspective on the Colquhoun & Sakmann (1985) paper published in The Journal of Physiology is that I’m not yet sure whether the conclusions of that paper were quite right." Do you really think I'd invent a claim like that? David Colquhoun (talk) 22:08, 2 October 2011 (UTC)David Colquhoun

Of course not, but everything here must be documented quite carefully and worded neutrally. I'm glad I could find a good reference to back up the statement. That way we avoid problems down the line. -- Brangifer (talk) 22:19, 2 October 2011 (UTC)

Next item of business: find URLs and more complete and precise descriptions for all the refs already listed. -- Brangifer (talk) 21:09, 2 October 2011 (UTC)

Great work with all the refs! I'll go through them and fix a few small matters of spacing and such per our MoS. -- Brangifer (talk) 02:00, 16 October 2011 (UTC)

Done with that. Now if you would go through it and wikilink any terms and expressions that will make this easier for non-specialists to understand. Only wikilink the first instance, not every instance. Assume that whoever is reading doesn't have a clue what this is about, and wikilink to articles which will help them understand what you're writing about. That will increase the value of the article considerably. -- Brangifer (talk) 02:15, 16 October 2011 (UTC)

I have wikilinked several terms and expressions. Are there any others? -- Brangifer (talk) 06:48, 21 October 2011 (UTC)

I'm pretty much finished with what I can do for now and would like to see if we're ready to proceed. -- Brangifer (talk) 06:52, 23 October 2011 (UTC)

Looks great to me. Thanks very much for your help David Colquhoun (talk) 07:25, 23 October 2011 (UTC)David Colquhoun

Okay, I've copied what's above into the article. I felt a need for a heading, so I've added one, but more appropriate wording might be best. -- Brangifer (talk) 07:51, 23 October 2011 (UTC)

Comment from David Colquhoun

I have no idea where we go from here, so I'll just explain the situation and perhaps you can offer some advice.

For most of my life I've worked on single ion channels and stochastic processes You wouldn't guess that from the present entry, but that's because it was set up in the first place by a graduate student in Toronto, as a result of a talk I gave to the Centre for Inquiry there. She kindly said that she thought I should have one. Of course she knew nothing of my science, and even after I'd suggested that it was worth a mention, it was still very minimal.

Even the skeptical bit isn't entirely accurate, because it concentrates on Alt Med and doesn't mention things I've done about managerialism (often very bit as irrational as Alt Med) and education policy.

The whole Alt Med thing is something that I got into after I'd been retired from the AJ Clark chair in 2004 (at age 68). It was only after that that I had the time to do it. I've enjoyed that and I'm still doing some science too, despite now being 75). Both you and Nomoskedasticity (surely a statistician with a pseudonym like that) have been kind enough to say nice things about my CAM activities, but they aren't most of my life -more like a retirement (so-called) hobby.

I'd thought for ages that my wiki page was very unbalanced so I decided, at last, to do something about it. Most of the biographical pages are written by someone anonymous (I'd love to know who really wrote some of them). I thought that, since nobody else was about to do it, I'd fill in some missing details, and so as to be totally honest about it I'd do it under my real name. To my dismay, what I'd thought to be the honest approach immediately got me a COI notice!

I expect the most people actually edit their own biographies, surreptitiously, under a pseudonym. In fact the Wiki policy seems to encourage. almost compel, that sort of dishonesty. It's something the editors should think about.

What I don't understand is that, if I don't fill in the details, who will? The vain and powerful may instruct a minion to do things under a pseudonym, but most people just don't bother. I never met a single scientist who'd spent time on a wikipedia entry. They just don't have the time for that sort of thing (and having tried, I can tell then it isn't a job to be undertaken lightly!). For example, many of my colleagues have commented on how poor the entry on acetylcholine is. None has bothered to spend the week it would take to rewrite it properly (and then, it seems, go through interminable wrangles too)

I'd be very happy for an expert referee judge whether I have been sufficiently neutral, including any existing wikipedia editor who has the necessary knowledge of Markov processes and single ion channels.

If something isn't done soon, I'll just give up on wiki processes, and delete my entire entry. - David Colquhoun (talk) 19:01, October 2, 2011 (UTC)

Fortunately there is no pressing need here. There is no libelous content. It's just a matter of adding more content so it's more thorough. The burden to do so isn't on you, but on other editors. We just need some help from you. Don't worry, you have lots of friends here. Enjoy a cup of tea. This will work out just fine. -- Brangifer (talk) 19:18, 2 October 2011 (UTC)

To start, let's take a look at what's above about your scientific career. I'll start by adding comments in that section. I hope I have a little time right now, but this can always stretch over several days. No big deal. -- Brangifer (talk) 19:23, 2 October 2011 (UTC)

Thanks Brangifer. I await with interest and will help in any way I can David Colquhoun (talk) 19:47, 2 October 2011 (UTC)David Colquhoun

Glad to be of help. Let's continue in the "editorial notes" section above. -- Brangifer (talk) 19:52, 2 October 2011 (UTC)

Looks like your in good hands David. Very interesting comments I can see your frustration, it would be nice to see an area on WP where people could appeal to editors to correct content they can't edit. Sgerbic (talk) 15:48, 3 October 2011 (UTC)

Sources for new material

Just a look at the pages that link to this article reveals possible material and reliable sources that can be added here. Some link to newspapers and other articles by Colquhoun, or articles that mention him, and these may be legitimate content here. I suggest that Dr. Colquhoun and others start digging! There's gold in them there hills....;-) -- Brangifer (talk) 21:57, 23 October 2011 (UTC)

Debrett's profile

Colquhoun has a FRS authorised biography in Debrett's (short online version here). It has a bit more detail on his academic appointments, honours etc. Randomnonsense (talk) 20:07, 6 March 2012 (UTC)