DNA structure: a history

So what's history behind the science of DNA structure? Neuroscientist Birgitta Olofsson, who is also making a documentary about Rosalind Franklin’s life and her role in the DNA story, spoke to Chris Smith...

Birgitta - So DNA in itself was not much of interest to a biochemist. It was mostly protein. But Jim Watson and Francis Crick were very keen to understand the genetic basis for heredity. That is what is information that's passed on to the progeny? And Jim Watson, being a geneticist, had very little understanding about chemistry, but in terms of chemistry, the structure of DNA, so the actual chemical structure of the DNA, had been known since a number of years. It was also postulated that the DNA was in fact the genetic material that's passed on into the offspring. And that was done in a set of elegant experiments, where a bacteria was infected by a virus, much like the coronavirus that we talk about a lot these days. And the virus consists of a protein structure and the DNA. And by selectively labelling the protein structure versus the DNA, they could show in these experiments that only the DNA that's taken up by the infected cells and then passed on in the progeny of the virus.

Chris - So they knew that DNA was critical to heritability, but they didn't necessarily know how. And they didn't know how the molecule was organised. And that's really the breakthrough of the early 1950s was working out that there actually was a structure there that could carry heritable information?

Birgitta - Yeah. So it was generally believed that DNA was too simple a molecule to be of this importance. Because in DNA there is only four letters, so to speak. The A, T and the C and the G. Meanwhile in a protein, a protein can be built up of 20 amino acids. So the complexity in the proteins favoured that proteins were in some combination with DNA, the genetic carrier. So it wasn't uniformly accepted that DNA was indeed the genetic carrier.

Chris - And what was the thinking at the time? There must have been rival groups. It wasn't just Watson and Crick's game, was it? There were presumably many other scientists who were all trying to understand this all at the same time and they must have all had rival theories.

贝,绝对。如果曾经有过一个比赛, the race was not between Rosalind Franklin and Morris Wilkins in Kings in London, and Francis Crick and Jim Watson up in Cambridge in Cavendish, it was actually between Linus Pauling, a protein chemist in the US, and the group at the Cavendish. It was postulated by both Linus Pauling, and Francis Crick and Jim Watson, that DNA could be a three strain molecule where the DNA bases were facing the outside and the phosphates facing the inside. And that would not be chemically and physiologically possible.

Chris - Why though was solving the structure so critical to all of this?

Birgitta - Well, by knowing the structure, you could immediately understand how the DNA could be replicated. That is that one DNA strand makes two new DNA strands in the progeny.

Chris - Where then did Rosalind Franklin enter the equation? Why is she so important to all this?

贝——所以罗莎琳德富兰克林came to Kings in 1951 and she was on her own fellowship. So she was not an assistant to Morris Wilkins who was there already working on DNA, but she was really an excellent chemist, a physical chemist, and she knew how to treat specimens. So she was able to see that the previous x-ray crystallography photographs that had been made was really a mixture of two forms of DNA. And she was able to separate out these two forms. So then you can study these two forms separately. And we know that one of those forms is the physiologically relevant, that one that is in our cells and that's called the B form.

Chris - So she managed to separate the DNA into a form that could then produce very nice pictures. And it's those pictures that were the insight into the structure.

Birgitta - Exactly. From those diffraction patterns on these pictures, you could see that it was a helical structure, repetitive units, and you can also see how many base pairs per turn in the unit and the diameter of the helix. But it was really Francis Crick and Jim Watson who worked out the antiparallel structure. So the two strands of DNA are going in the opposite direction, plus this base pairing. So hydrogen bonds between these letters, so to speak, in the ladder of DNA.

Chris - And is that the basis of this so-called famous photograph 51? Is that the one that's the very famous picture we see in textbooks and things, it almost looks like a zebra crossing in three dimensions.

贝,绝对。So photo 51 was called photo 51, simply because it was number 51, and it's of the B form. And it was Rosalind's PhD student, Raymond Gosling, who took that. And when Rosalind was about to leave to Birkbeck from King's College, he showed that to Wilkins who later showed it to Jim Watson. So they had access to this photograph.

Chris - And once she took that amazing photograph - and we will learn a bit more in a second about the technique that she used in order to take that photograph that was the clincher that revealed the structure of DNA, as you're saying - did she carry on doing this sort of work? What happened to her after this?

Birgitta - So Rosalind was at King's only two years. And then she continued at Birkbeck where she used x-ray crystallography to solve structures of viruses. So she was in fact with her group, the first person to solve a viral structure, which was the tobacco mosaic virus. And her tombstone does not tell anything about DNA, it's for the virus work.