tRNA is transfer RNA and this is what's involved in carrying... in protein synthesis... protein synthesis takes place on the ribosome and the... there's a molecule. And what happens there is that the... the genetic code tells us that three amino acids are specified... sorry, three nucleotides are used to specify an amino acid. And the... this recognition takes place by a molecule transfer RNA which recognises the anti-codon in the messenger RNA. At the same time, it carries at one end of the tRNA and the other end it carries an activated amino acid. That means one with a high energy bond which you can easily split off. And so this links... this links together the two subunits of the ribosome, the 30S and the 50S. And the 30S is where the code is read and the 50S is where the amino acid, which is carried by the tRNA, is... is... linked to the next one in the chain. It's the whole beautiful picture of protein synthesis, so the question is: what is the structure of tRNA? And Francis Crick came to me because we were the only people in the lab who knew something about RNA because of the TMV work. He said, 'We have to determine the structure of... of tRNA'. It was, you know, next thing on in the advance in molecular biology. Now, the... the formula for tRNA had been worked out and if you write down the sequence of the 70 odd nucleotides in transfer RNA, they form what looks like a clover leaf, that's four... four double helical regions connected together by loops, so-called 'clover leaf structure' which Holley worked out. Now, I assumed, and most people did at the time that these four bits would be like, some moveable object, one arm would carry the... amino acid, one arm would carry the... would be the... would carry the anti-codon which was on the other arm. And the other bits were involved in recognising the ribosome. So I imagined it was something like this with the four arms carrying and it gets into the ribosome. Francis said to me, Crick said to me, 'Oh, it's not going to be like that.' 'So what's it going to be like?' He said, 'It will be a single molecule, a three-dimensional structure.' And I said, 'Well, if that's the case we have to crystallise it.' And he said, 'Yes.' And you know there's... well, the... so we began, there was Brian Clark was in the lab working in Francis Crick's division and he was making large quantities of tRNA. And we decided to... he wanted to crystallise what's called met-tRNA which is involved in the initial... initiation of assembly. I thought that you couldn't put all your eggs into one tRNA, we just are trying to crystallise different tRNAs. There was a man called Cramer, a German, who was working on these things in Gottingen, Friedrich Cramer. And he had... he had got some very small crystals of... of one of the tRNAs. I decided that we would try, we need large quantities, and when you try to purify the tRNA they came off at different... different position of the exchange chromatography. But there's one tRNA which ran far ahead of all the others, that was, phenylalanine tRNA. Not phenylalanine... Which one?
[Q] It was phenylalanine.
Yes, phenylalanine tRNA, of course, sorry, phenylalanine tRNA. And... and so I said, 'Oh, let's work on this one which you get large quantities, it's free of all the others.' And by that time a lot of people were starting to try the crystallised tRNA, Alex Richard's lab, Jacques Fresco's lab. Jacques Fresco came to... the next thing on in, the next obvious thing, it's not often there's a period in science where the next step is obvious; not often, sometime there is such a period and this was one of those. And Jack Fresco came to the lab to try and find out what we were doing, a bit of a cheek now that I come to think of it. Anyway, because we were trying to do it.
[Q] Well, he had grown.
He had grown... he had grown crystals, a mixed tRNA.
[Q] Yes.
And I couldn't believe it was mixed because they were different species, because not phenylalanine it was some other tRNA. And he was convinced that, I said, he came to the lab and he wanted to work with us. So that was all right, but, in fact, it turned out that what he... what he'd grown was not a mixture at all, it was one particular species, I think it was Lysine tRNA. But he... he was trying to grow the crystals by evaporation from dioxane, it's volatile, it's not the way, you can't control things that way.
