THE CENTRAL FACTS FROM THE COURSES YOU ALWAYS MEANT TO TAKE, IN 25 LECTURES

Week 3 Day 1 DNA : Visiting Lecturer: David Bodanis
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The Independent Online
The promise of modern science had been to unveil all of God's secret doings, but that promise certainly hadn't entered into the minds of Francis Crick's teachers at his schools in 1920s Britain. Didn't he realise that no one would ever explain the mystery of life, they asked, sending this science-obsessed youngster back to the chapel.

Twenty-five years later, as one of the many trained physicists disgusted by wartime research who had turned to biology, he was naturally attracted to the strange molecule called DNA that people were talking about. There were hints that DNA was what controlled each cell's own operations - that this was the long-shrouded control centre - but there was a nagging problem about size.

When a digestive cell made insulin, it couldn't be because there had been little vials of insulin dangling there inside the DNA. A cell has to make hundreds of different chemicals, and there'd be no space for them all - it would be like Jonathan Swift's characters who had to carry a little rock around with them to point to when they wanted to talk about a rock, and a clock when they wanted to talk about a clock, and so on.

The only way out would be if there were tiny blueprints stored in the DNA floating in that cell's depths, far smaller than the actual worker molecules that had to be produced.

Crick joined with a young American, James Watson, and by 1953, after much seminar-going, model-building, and a certain amount of surreptitious glancing at other people's research, they had it: a neat two-page paper that finally showed how the miniaturisation could take place.

Each DNA molecule was shaped like a long twisted ladder - the famous "double helix" shape. The outsides of the ladder were largely ordinary sugars, but the inside - the inner rungs you'd have to step on to walk up the twisting ladder - were made of short, stubby chemicals that could be ripped in half, Velcro-style. Let a section of the DNA grindingly pull apart, and those stubby inner-rung halves were exposed, gaping up like the dots and spaces on the feed sheet for a player piano.

All you'd need was for some tiny messenger to slip into this briefly opened gap, take a copy of the long row of broken rungs and hurry back out. Chemical clusters would swarm up to it, matching the coded picture in the now-closed DNA, and the needed worker molecule would get built.

Now molecular biology was hot. While physics had become increasingly difficult, increasingly abstract, here was this new field, where everything was easy to visualise - who could have a problem with twisting ladders, or speeding messengers? - and fresh discoveries seemed just waiting to be made.

At first the image of a perfect all-controlling DNA molecule at the centre prevailed. Researchers found that some of the ladder-rung sequences weren't used to build worker molecules, but served as signposts for orienting the messenger molecules when they landed. Other ladder chunks built chemicals that registered what was going on in the cell, and forced the signpost regions to work faster or slower as needed.

The great molecule could even fix itself. Certain stretches carried the blueprints for repair vessels that were sent gliding out to fix rungs that had been broken by incoming cosmic rays, or ordinary body heat. It was the ultimate refinement of Newton's vision, now come true: the human body was a clock that didn't even need an outside Creator to wind.

Crick was proud, and Watson was insufferable. He took up a faculty position at Harvard, and immediately tried to get ecology banned from being researched or taught, for what good could such fuzzy, large-scale studies ever be?

Gradually though the vision changed. The ancient floating DNA molecule inside us wasn't as perfect as thought. Long stretches of the ladder were quietly rusting away, broken after failed repair efforts in previous generations. Other stretches had just slipped in over evolutionary time, getting this free ride forward through the generations in our body. In many species there could even be ladder stretches that jumped entirely out of position, landing at far distant locales. If these ladder sections switched on whatever they landed next to, then uncontrollable growth orders could start being sent out - cancer might appear.

Today Watson is the grand old man in his field, and a leader in the Human Genome Project - the effort to detail every one of the blueprint rungs in our DNA. Some people object to the project as being too narrow, but Watson will hear nothing against it. He remains as immodest as ever, but then, he has a very great deal to be immodest about. Crick, himself, has long since left DNA research. He has moved to neuroscience, for people had been irritating him by saying there were mysteries in the mind that perhaps could never by unveiled by science.

Tomorrow: Anthropology

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