Crick & Watson--a disaster for biological science??
Here's a controversial statement that came up yesterday in a discussion I had with some polymer scientists:
That Crick and Watson's 'revolutionary' derivation of the structure of DNA, far from being the triumph of 20th century science, was actually the biggest disaster to hit biology since biological science began.
Controversial--perhaps over the top--but not, I think, way off the mark. What Crick&Watson did (and subsequent even more complex structural measures such as Max Perutz & John Kendrew's first protein structures, in the 1960s) was establish the structural paradigm in biology. What counts is the way the atoms are arranged in the protein, the way the bases are stacked in the doube helix.
This 'structural bias' came naturally to most of these guys, as their background (or at least the Cambridge Cavendish background they worked within) was physics. Physics had said, since the turn of the century, that all was a matter of atoms. Moreover, physics had shown how to measure where atoms were relative to each other (at least in crystalline, ordered solids): use the characteristic scattering of Xrays. So a natural next step was to use said Xrays to look at where the atoms were in DNA and proteins. This sort of data was what Crick, Watson et al interpreted to get at the shapes of their frozen molecules.
But. Biology's machines, such as proteins and DNA (roughly classified as 'workhorses' and 'memory store' if you like), have to move to function. No surprise there--machines have moving parts. An internal combustion engine needs pistons that move if it's going to drive wheels. A steam engine needs a piston moving in a cylinder if it's going to pump water out of a mine (a la Newcomen back in the 18th century) or drive a train along a track. Proteins too are machines that 'harvest' chemical energy inside the cell, turning it into 'work'--forces to make things move. So proteins have moving parts. And it is in fact the way those parts move that is the real key to function. The structure of a 'frozen' protein only tells a small part of the story. It's in the dynamics that all the interesting...well, all the dynamic stuff happens.
So when Crick, Watson, Perutz and all the rest concentrated biologists' and biochemists' minds on structure without motion... perhaps it was (with hindsight) a bit unfortunate.
Nowadays researchers are coming up with ways to measure protein motions directly--using fluoresecent bits tagged onto parts of a protein, for instance, whose behaviour changes depending on just where they are relative to the rest of the protein body, so that watching that fluctuating behaviour is akin to watching the protein itself wriggle and twist. So at last the structural paradigm is starting to be matched by its necessary dynamic subtext.
But what does this have to do with middle world? Proteins and DNA are middle world-sized objects: large molecules made of many thousands of atoms. Because of that, and because in the cell a protein is surrounded by a sea of water molecules that keep bombarding it from all directions, proteins are inherently restless--subject to furious fluctuations otherwise know as Brownian motion ( after Robert Brown of course... see Chapters 1 and 2!!) Protein function can't really be understood from structure alone--you need a delicate balance of chemistry (structure) and motion (dynamics, fluctuations) to come up with such an exquisite machine. It's in this balance between the rules of chemistry and the randomness of middle-world motion that the secrets of protein function seem likely to lie.
Structure is important. But not so important that it should have blinded so many scientists to the dynamic, furiously fluctuating reality of life's machines! Down with the beautiful static scuplture of the double helix! Here's to the rise of motion!
That Crick and Watson's 'revolutionary' derivation of the structure of DNA, far from being the triumph of 20th century science, was actually the biggest disaster to hit biology since biological science began.
Controversial--perhaps over the top--but not, I think, way off the mark. What Crick&Watson did (and subsequent even more complex structural measures such as Max Perutz & John Kendrew's first protein structures, in the 1960s) was establish the structural paradigm in biology. What counts is the way the atoms are arranged in the protein, the way the bases are stacked in the doube helix.
This 'structural bias' came naturally to most of these guys, as their background (or at least the Cambridge Cavendish background they worked within) was physics. Physics had said, since the turn of the century, that all was a matter of atoms. Moreover, physics had shown how to measure where atoms were relative to each other (at least in crystalline, ordered solids): use the characteristic scattering of Xrays. So a natural next step was to use said Xrays to look at where the atoms were in DNA and proteins. This sort of data was what Crick, Watson et al interpreted to get at the shapes of their frozen molecules.
But. Biology's machines, such as proteins and DNA (roughly classified as 'workhorses' and 'memory store' if you like), have to move to function. No surprise there--machines have moving parts. An internal combustion engine needs pistons that move if it's going to drive wheels. A steam engine needs a piston moving in a cylinder if it's going to pump water out of a mine (a la Newcomen back in the 18th century) or drive a train along a track. Proteins too are machines that 'harvest' chemical energy inside the cell, turning it into 'work'--forces to make things move. So proteins have moving parts. And it is in fact the way those parts move that is the real key to function. The structure of a 'frozen' protein only tells a small part of the story. It's in the dynamics that all the interesting...well, all the dynamic stuff happens.
So when Crick, Watson, Perutz and all the rest concentrated biologists' and biochemists' minds on structure without motion... perhaps it was (with hindsight) a bit unfortunate.
Nowadays researchers are coming up with ways to measure protein motions directly--using fluoresecent bits tagged onto parts of a protein, for instance, whose behaviour changes depending on just where they are relative to the rest of the protein body, so that watching that fluctuating behaviour is akin to watching the protein itself wriggle and twist. So at last the structural paradigm is starting to be matched by its necessary dynamic subtext.
But what does this have to do with middle world? Proteins and DNA are middle world-sized objects: large molecules made of many thousands of atoms. Because of that, and because in the cell a protein is surrounded by a sea of water molecules that keep bombarding it from all directions, proteins are inherently restless--subject to furious fluctuations otherwise know as Brownian motion ( after Robert Brown of course... see Chapters 1 and 2!!) Protein function can't really be understood from structure alone--you need a delicate balance of chemistry (structure) and motion (dynamics, fluctuations) to come up with such an exquisite machine. It's in this balance between the rules of chemistry and the randomness of middle-world motion that the secrets of protein function seem likely to lie.
Structure is important. But not so important that it should have blinded so many scientists to the dynamic, furiously fluctuating reality of life's machines! Down with the beautiful static scuplture of the double helix! Here's to the rise of motion!
posted by mark haw at 6:48 pm
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