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!

Professional curiosity?

Just a mention of a recent article I wrote for the website lablit where I discuss what I think is a problem with modern-day curiosity: that asking questions and seeking answers about how the world around us works has become the province of experts, scientists--professionals of curiosity if you will. Of course, it may always have been this way... unless you count people like Faraday and Dalton; or the botanist Robert Brown, and all the amateur botanists and naturalists who around the end of the 18th/beginning of the 19th centuries laid the groundwork for Darwin's theory of natural selection.

These people put together a database not conceptually different from the Human Genome Project: most of them without formal training or qualifications. What they lacked in university certificates they made up for in the willingness to investigate, examine and question the nature of the world around them.

Do people do this anymore? Perhaps we know our world too well now for "ordinary" people (i.e. without the backing of vast laboratories, funds and high-spec equipment) to find out anything new about it?

Actually I don't think so--there are umpteen basic everyday phenomena that we are really still very puzzled by, and research papers are frequently published in top journals based on rather simple observations--the simpler the more striking, it often seems. There is still a lot of stuff out there that simple careful observations and intelligent thought can throw light on.

One place that the modern version of 'amateurs of botany' might profitably go to do a bit of 'phenomenon-botanizing' is the computer: the astounding power available even in cheap computers these days means that calculations, simulations and investigations of very complex phenomena are relatively easy. Witness such simple models such as 'cellular automata' and the complex behaviour they can reproduce... (Nothing new: games like chess and go have been generating huge complexities out of simple rules for centuries...)

Academic literature, however, still presents a problem, perhaps the major stumbling block to amateurs of curiosity contributing to the way we understand the world. How can a non-expert know what is the 'state of understanding' of any phenomenon when science is almost invariably described in terms comprehensible only to the bare minimum of specialists?

In the media we hear phrases such as 'scientists think such-and-such' as if we all belong to a club and go around mentally juggling the same ideas. In reality there is no such thing as this kind of generic scientist anymore (if there ever was). Most of us, when ill-advised enough to take a short hop outside our research speciality, are quickly lost--not by the impossibility of understanding, but by the impenetrability of jargon. (This problem is certainly not confined to science of course...)

This ought to be where 'popular science' comes in... But more on that story later, as they say.

Reviews etc

Reviews etc

Here is the text from a recent review in this month's Chemistry World:

The incessant dance
Review of 'Middle World' by Carol Stanier, (c) Royal Society of Chemistry

The untidiness of my bedroom is due to the second law of thermodynamics. Namely, the world tends towards increased entropy and disorder, and there are more ways to make a bedroom untidy than there are to keep everything in its rightful place. This is just one of the curious but instantly understandable analogies that Mark Haw uses to explain some of the complex physical concepts necessary to understanding Brownian motion.

The Middle world, according to Haw, is the tricky region between atoms and molecules, and the bulk assembly. It is a world occupied by such unlikely bedfellows as DNA, plastics, pollen, and the constituents of mayonnaise and shampoo. It is here that the incessant dance described by Robert Brown takes place.

As we journey through Middle world we meet (as one might expect) numerous Nobel prize winners and other eminent scientists, but also philosophers and even playwrights, their work set in context of the story. Peculiar and intimate details of their lives, such as Marie Curie’s scandalous affair with Paul Langevin, give this tale human as well as scientific interest.

There have been numerous books published in the past few years on nanotechnology and the history of science, several of which are listed in the further reading, but Middle world is certainly one of the most readable of these. It is written in such a way that it should be simple for even those with very little background in science to understand. Haw’s excellent descriptions involving rice pudding and jam (have you ever tried unstirring the jam from a rice pudding?) and giving oranges to school children (to demonstrate energy distribution in gases) ensure that concepts normally encountered only at degree level are just part of a riveting story that started with a botanist called Brown.