In the early '70s the... there was a man... John Hindley, do you remember him?
[Q] Yes.
He came to the lab, he joined us in the last few years at Birkbeck, the last year at Birkbeck, he came with to Cambridge. I've forgotten whether he was... he was a sort of Post Doc And I thought at the time I'd been reading about other things, in particular I'd read quite a lot about DNA and about DNA protein complexes including protamines, which are found in sperm. And... and there were the papers by [Vittorio] Luzzati and by [Maurice] Wilkins, separate papers, where they were trying to pull fibres of chromatin. And at about this time, people discovered that the histones, the molecules which are involved in packaging DNA inside chromosomes, the so-called histones were of two types, they were called arginine rich histones and lysine rich histones. They were just... the sequences weren't known at the time but they went... and you could separate them in different ways, you can make them relatively easily. So I got John Hindley to make all these different types of histone, they were mixtures. The arginine rich are in fact later called H3 and H4 and the lysine are H2 and H2B which are the four out of the five histones which are found, there's a fifth one called H1, which I'll mention later. And the... the... so we pulled fibres, I actually pulled the fibres, I mean, John did and I simply put a needle in. I said to John, 'Pull it out', and said, 'This is what you do pull some fibres.' But making different mixtures of DNA, different mixtures of DNA and... and the histones in a different concentration because we'd know what the stoichiometry would be. So we did this and we got fibres and well, we just got patterns, which were no better than patterns which were obtained by Wilkins and Luzzati using all the histones; I thought there might be some differentiation because they clearly were a different role. Of course, we now know what they are but at the time we didn't. So I didn't proceed with it because I obviously couldn't do any better than that. And then Francis Crick went to a meeting in Port Buc in the South of France on what turned out to be chromatin. It was about packaging of DNA and so on and he came back and told me, you know, 'There are only... there aren't 25 different kinds of histones as people believed', there was a husband and wife team in Edinburgh called the Stedmans who worked on this. And he said that they now know that there are only four types of histones, H3, H4 and H2 and H2B. These are being cloned and some sequences have been worked out in the United States, cloning had come in by this time, you see. And the fifth histone H1 and all the others, the 25 were post synthetic modifications of histones in acetylated forms and things of that sort; lots of acetylated, mostly the acetylated forms. Now, we... we knew the... but this made the problem sort of tractable. So when Roger Kornberg said he'd like to come and work on some new problem... a messy problem, which he could help sort out; I said, 'I've got the very thing for you, chromatin.'
