Talk:Peter D. Mitchell

message: Well, Saier's biography of Peter Mitchell has many good pictures in it, and I did consider to take some pictures from there. But the problem is that they are relatively recent (after 1923 anyway), so I decided against that because of copyright issues. If you want to look into that, perhaps send an email to Saier to ask him about it, be my guest. JdH 10:37, 8 May 2006 (UTC)
thread_title: Untitled

message: The present version:
:In the 1960s, ATP was known to be the energy currency of life, but the mechanism by which ATP was created in the mitochondria was assumed to be by substrate-level phosphorylation.  Mitchell’s chemiosmotic hypothesis was the basis for understanding the actual process of oxidative phosphorylation.  
The previous version:
:It was well known in the 1960s that ATP was the energy currency of life, but the mechanism by which ATP was created (“oxidative phosphorylation”) was entirely unknown and quite mysterious.
I think that the current Wikipedia version states the facts incorrectly, and that the previous version states the facts more accurately.  It is true that the state of the art in the 1950s (not the 1960s) was that “substrate-level phosphoylation” was assumed to be the only possible mechanism of ATP synthesis.  By the 1960s, however, it had became obvious that this “theory” was a dead end, and that a new theory was needed..  The mechanism of ATP synthesis was quite mysterious.  One experiment after another failed to find any trace of the classical “high-energy intermediate” (also known as “squiggle”) that would explain oxidative phosphorylation.  This is where Peter Mitchell came in.
I can see how a teacher might, for didactic purposes, simplify  history for his students by saying that the ongoing theory at the time was substrate-level phosphorylation.  But in fact there was no ongoing theory at the time.  To say that substrate-level phjosphorylation was “assumed to be” the mechanism of ATP synthesis is a mischaracterization of the “Oxphos Wars.”  Students who have been taught this incorrect piece of historical trivia need to learn a little more about the subject before they start revising Wikipedia articles.
I recommend reversion to a previous version of the article.
:Too be frank your criticism of my edits is getting very personal. I am happy to work with you here but can you stop with this kind if stuff: "need to learn a little more about the subject before they start revising Wikipedia articles."? This is an ad hom argument and is pretty unwarranted given the subtlty of your criticism. I think what I wrote can be improved but i think if we are going to work towards improvement, just reverting to your old version does not cut it.  There were good reason i made the edits throughout the article, primarily because your admitted hero worship was obvious.  It was too POV for an encylopedic content. 
:With regard to the sentence you discuss above. The facts as stated in your own version seem to be unclear, for example: "but the mechanism by which ATP was created (“oxidative phosphorylation”)".  This gives the impression that all ATP comes from oxidative phosphorylation. Obviously this is not what you meant but it's how it comes across. The following part of the sentence continues, "was entirely unknown and quite mysterious." In my opinion this is too much hyperbole and should be toned down. Some thing along the lines of: "by the 1960's scientists had failed to discover a ............ and were struggling to identify the mechanism for the ATP produced during aerobic respirtation".  That is just off the top of my head, but it seems a more appropriate style for an encylopedia. David D. (Talk) 03:59, 21 August 2006 (UTC)
replies: text: Thinking a bit more about this: I think the problem in the early 1960s was that the field of ox phos had been subdivided into little pieces. There were people who were interested in the bioenergetics; they wanted to understand how the energy is transduced for synthesizing ATP. Then there were enzymologists, who wanted to understand the protein structure and the mechanism of the specific enzymes involved. And then there were microbiologists who were interested in membrane physiology and transport processes.  So all the pieces were in place, and all the right questions were being asked, but what was lacking was the big picture, the vista so to speak. People couldn't see the forest through the trees. Biochemists and biophysicists like to analyze the problem in separate little pieces, and after they understand the little pieces integrate it into a big picture. But that analytical approach does not work for ox phos.  Mitchell's chemiosmotic hypothesis provided the big picture, but people had a hard time to recognize that because he did not provide the answer for the specific sub-questions they were interested in. JdH 15:22, 21 August 2006 (UTC)
thread_title: REVISION 1.0.0

message: Peter Mitchell may have been right for the wrong reasons, but this in no way detracts from his genius.  You mention his background.  I think that his background is well worth knowing about in more detail. 
As a graduate student at Cambridge, Peter Mitchell 
:. . . would carry out a large number of small, rather inconclusive experiments which enabled him to develop his theory of what was occurring.  Then he would design one massive all-inclusive experiment based on the results of all the preliminary tests – and that, if it worked, was that.  To any one outside of the department, much of his early work seemed to be incomplete because he left out those tests or controls which were discarded during the preliminary work.  I well remember sitting next to Hans Krebs at a meeting of the Biochemical Society when Peter first gave a major paper on his work on energy transfer . . . Krebs steadily became more and more incensed and muttered  “But in he hasn’t done the controls.”
Mitchell submitted a PhD thesis that was rejected.  He flunked Cambridge.
Apparently only a few pages of his original thesis survive, but I think they are extremely telling:
:In the second paragraph, Mitchell cites  Heraclitus, along with Seneca’s comments on Heraclitus’s famous dictum that one cannot step into the same river twice.  He notes that the same is true of a human, whose identity persists but whose substance is constantly being changed.  In the same paragraph he cites Walter de la Mare’s little verse about Miss T. that includes the lines “Whatever Miss T. eats, turns into Miss T.” . . . This was followed by a mathematical theory of diffusion and distribution of substances within cells . . .
During his philosophical period, Mitchell sought the professional opinion of the Department of Philosophy at Cambridge.  He is quoted as saying
:There was a man called Wisdom in those days who more or less told me I was a nit.
In other words, Mitchell was a serious contender from the outset, a fact which a number of the Grand Old Men in science at the time came to appreciate only in retrospect, to their everlasting regret.
The above quotations are from Wandering in the Gardens of the Mind, a 324-page biography of Peter Mitchell by John Prebble and Bruce Weber (Oxford University Press, 2003).  This, together with Opening Pandora’s Box, contains essentially all of the original source material that is available to the general reader (e.g. yours truly).  If I get around to it I would like to make a further case regarding the description of Mitchell’s theory in the present version of the Wikipedia article, but for the moment I stand by my original assertion that the entire article should be reverted.
Btarski 03:23, 21 August 2006 (UTC)
replies: text: I find it hard to find objective evaluations of Mitchell's contributions; the people who write the histories were too much personally involved. In particular, I would like to hear the story from  "the other side", i.e. from Chance and Boyer, if it exists.  Be that as it may, there is a highly unusual comment from Bo G. Malmström in Nature (). Unusual in the sense that Malmström was the chairman of the committee that recommended to award the 1978 Nobel Prize for Chemistry to Peter Mitchell. I always thought that the Nobel prize committees never give a public justification for their recommendations, but in this case they made an exception. The bottomline: The committee was well aware of the fact that Mitchell was wrong about how the proton gradient is created (proton pumps rather than redox loops) and how it is utilized to make ATP (conformational coupling rather than mass action). This is why the academy's citation read rather vaguely "for the contribution to the understanding of energy transfer through the formulation of the chemiosmotic theory". JdH 07:05, 21 August 2006 (UTC)
thread_title: Discussion (Cont’d)

message: I think that the essence of Mitchell’s theory was the recognition that biological membranes (and hence “vectors” across membranes) play a central role in all living organisms.  
In the 1960s, the controversy over Hodgkin and Huxley’s theory of the action potential had finally been resolved in their favor.   Every biologist in the1960s knew about this, but only one (Peter Mitchell) took the next logical step.  Why do all cells, not just neural cells, have a membrane potential?
Mitchell’s “vectorial” theories supplied the missing piece in what was then the main conundrum in an entirely separate area of science, the biochemistry of ATP synthesis.  To find the “squiggle,” the high-energy intermediate, the biochemists needed to look no further than cell membrane itself, which already had a built-in energy potential.
Btarski 20:34, 21 August 2006 (UTC)
thread_title: Discussion (Cont’d)