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Tuesday, October 20, 2009

Ode to Peter Mitchell

Everyone knows about Watson & Crick and Albert Einstein and a few other famous scientists who have discovered something new.

But few people know Peter Mitchell and why he is more important than most other scientists.

Mitchell is one of a handful of scientists who really have changed the way we think about a subject—in this case how energy is produced in living cells [see PETER MITCHELL

Nick Lane has just published an article in New Scientist that highlights Mitchell's contribution to biochemistry. Not only did Peter Mitchell show us how chemical energy is produced in living cells, he also provided tremendous insight into how it must have worked when life first began [Was our oldest ancestor a proton-powered rock? ].

Here's the opening paragraphs of Nick Lane's excellent article. You really should read the whole thing—buy the magazine if you have to.
PETER MITCHELL was an eccentric figure. For much of his career he worked in his own lab in a restored manor house in Cornwall in the UK, his research funded in part by a herd of dairy cows. His ideas about the most basic process of life - how it gets energy - seemed ridiculous to his fellow biologists.

"I remember thinking to myself that I would bet anything that [it] didn't work that way," biochemist Leslie Orgel wrote of his meeting with Mitchell half a century ago. "Not since Darwin and Wallace has biology come up with an idea as counter-intuitive as those of, say, Einstein, Heisenberg and Schrödinger."

Over the following decades, however, it became clear that Mitchell was right. His vindication was complete when he won a Nobel prize in 1978. Even today, though, most biologists have yet to grasp the full implications of his revolutionary ideas - especially for the origin of life.
I wish this weren't so but I'm afraid the last statement is correct. It's not only biologists who fail to grasp the implications, there are even biochemists who don't understand chemiosmotic theory and don't teach it correctly in undergraduate courses.

Some of the most popular biochemistry textbooks didn't explain it properly until their most recent editions in 2006 and 2007. That's shocking.

Peter Mitchell deserves a lot more credit than he gets.

The molecule shown above is ubiquinone:cytochrome c oxidoreductase, also known as complex III [PDB 1PP9]. It is one of the most important enzymes in all of biology. It's structure provided the ultimate proof of chemiosmotic theory since it catalyzes the Q cycle, the key step in creating a proton gradient across a membrane [see Ubiquinone and the Proton Pump].

Every student who takes an introductory biochemistry course should be intimately familiar with this enzyme and how it works. In fact, if they're not, you can be sure that the biochemistry course was not taught properly.


Psi Wavefunction said...

I remember this enzyme always being presented as this random little thing hanging out in the membrane, overshadowed by the much larger neighbours (and larger = more interesting, obviously)

[rant]As a matter of fact, I can vividly remember this stuff being traumatically BORING. Even though in principle, the process that provides life access to energy to...happen... should actually be quite interesting. I've yet to come across any chemistry-related course being taught properly here, to be honest...

Our 300 lvl biochem (more macromolecular than the preceding intro course) is just *memorising* medically-relevant mammal-specific pathways, and which kinase phosphorylates which residue on which other random protein. I loathe biomed and anything to do with it, but this is labelled as a required 'general' course. But that's the least of the problems - they have turned something that could be fascinating like cell signalling and cell cycle regulation and turned it into a giant cramfest. And they try to cram so many facts (and factoids) into a three month course that there's simply no way you can soak all of that in properly. On top of 4-5 other courses, which also tend to be run exactly the same way. After all, they do explicitly cater to [vulgar adjectives] pre-meds. Because nothing can be as comforting as knowing that your doctors got there by memorising the textbook...

Also, that biochem course is where I recently heard 'This [ridiculously complicated kinase kinase kinase ... kinase pathway] evolved because it provides evolution plenty of elements to tweak with, so it can save energy when making new pathways'. TWITCH. I had to physically cover my mouth to not blurt out a stream of profanities... (to be fair, that was a TA during a tutorial. Still scary!)

The worst result of generally crappy teaching in a particular subject is that it turns you off from learning it properly on your own. I'm beginning to think it's much better to not be taught AT ALL than being taught shittily...

One more concept added to the "To-Relearn List", thanks!

Timothy V Reeves said...

I noted these quotes from Lane's article:

Mitchell dubbed his theory chemiosmosis, and it is not surprising that biologists found it hard to accept. Why would life generate energy in such a complicated and roundabout way, when simple chemical reactions would suffice? It just didn't make sense.

There is no doubt that the common ancestor possessed DNA, RNA and proteins, a universal genetic code, ribosomes (the protein-building factories), ATP and a proton-powered enzyme for making ATP. The detailed mechanisms for reading off DNA and converting genes into proteins were also in place. In short, then, the last common ancestor of all life looks pretty much like a modern cell.

There are interested “fishing” parties out there who may well be reeling in those quotes!

DK said...

To Psi Wavefunction:

When you do get time to "relearn" this, I have a suggestion: try to learn what was firmly KNOWN before the chemiosmotic hypothesis. Once you really do that, you will appreciate what a breakthrough in understanding things was Mitchel's theory. And how fundamental it is. The rest is simple math that you don't even need to memorize.

Gogarten Lab said...

Milton Saier wrote a book on Peter Mitchell (biography). It is available online at

Anonymous said...

It was indeed a timely article. I knew all about chemiosmosis but not about the possible origin of life connections. I am off to see if the idea is stimulating much simulation work, but if you have any leads about that I'd be pleased to see them