Watson and Crick paper. Facebook Twitter. Post a Comment. Previous Post Next Post. Learn more Ok. Contact form. At the time he was working it was not known that genes were composed of DNA. Instead, it was generally accepted that the 20 amino acids which compose the protein in the cell were the carriers of genetic information. Scientists reasoned that because there were so many different kinds of amino acids in the cell, they could combine in enough different ways to form a sufficiently complex basis for the gene.
It was only in when O. Avery and his co-workers showed that DNA was a key agent in biological transformations that Chargaff realized that DNA could in fact be a major constituent of the gene. Two major facts were already known about DNA. The first was that it is contained in the nucleus of every living cell. The second was that, in addition to sugar 2-deoxyribose and phosphate, DNA is composed of two bases: pyrimidines, of which there are two types cytosine and thymine , and purines, of which there are also two types adenine and guanine.
In addition, two important experimental methods involving paper chromatography and ultraviolet light absorption had recently been developed. To test the idea that DNA might be a primary constituent of the gene, Chargaff performed a series of experiments. He fractionated out nuclei from cells. He then isolated the DNA from the nuclei and broke it down into its constituent nucleic acids.
So much of this pivots around this one discovery. And I think I wouldn't be doing justice to this finding, which you all have heard about for years and years, if I had let you walk away from here thinking this was too young geniuses who sat down in a room with some crystallographic data and emerged with a structure that sort of changed the course of the study of biology.
And, as you can see, changes our society and everything else. There are a couple of accounts of this, there are numerous accounts. This was Horace Judson's effort to try and put together a history of this happening. And with all history he's ultimately -- You know, there are some judgment calls by the historian, but this one certainly he tried to be pretty fair-handed and even-handed and he tried to get at the heart of what was going on.
Jim Watson's a very colorful character, quite brash particularly when he was younger, and that's reflected in this book. It's an interesting read. And there are now a lot of other books. But what I did, just to try and do this in about a minute or two, was I took a couple of the key things that happened during their adventure of trying to work out the structure of DNA and just kind of ran some of their missteps together, because even though this was a marvelous discovery it just didn't happen.
So they started out, they were inspired by Linus Pauling's discovery of the alpha helix. And I don't know if you can remember the story, but what Pauling decided to do when he was lying in bed and with a strip of paper trying to work out the structure that was giving these reflections in the crystal structure, he said I'm going to start by ignoring the side chains.
So that was a brilliant move in the case of the alpha helix because he was then able to figure out that that hydrogen bond between the carbonyl and the amino group, you could see how if you got helix going it would repeat at exactly the way that would give the reflections that were observed in the crystallography. So that was how Watson and Crick sort of did it. Linus Pauling had shown the way. So they decided they would ignore the side chains of DNA. So they started out by saying we won't consider the ATs, the Gs and the Cs.
Well, given what you know about the structure of DNA that was not a helpful move in trying to work out the structure of DNA. Another thing, for example, that happened was that Jim Watson has no lack of self-confidence.
And so it turned out when he went to hear scientific talks he didn't take notes. And so he went to hear a talk on x-ray crystallography given by Roslyn Franklin, but he didn't quite remember the numbers right. He got the facts a little jumbled, and he and Francis spent a while trying to design models to data that wasn't the right data.
It was just not quite remembered right, so there was kind of an inefficiency there. And then Jim had a bias almost to the end that the phosphate backbones they knew would somehow be on the inside and the bases would be on the outside of the structure.
So if that's your sort of starting place then it's sort of hard. So Watson, excuse me, Francis Crick was beginning to suspect that maybe the bases were important. So he hired a young mathematician. And the young mathematician came back and said that he thought G might go with C and A with T. And given what happened here you might have thought that a light bulb would have gone off, but it didn't.
And, in fact, Chargaff visited them and the light bulb went off for nobody. And, in fact, Chargaff wasn't a terribly big fan of what Watson and Crick were trying to do.
So the pieces are piling up but still not there. Then a big experimental advance came from Roslyn Franklin. And that was she discovered that the DNA that they had been diffracting was actually a mixture of two forms. So there were actually two structures in the mix that were contributing to the diffractions.
And so now this gave a much clearer diffraction pattern, and that's the diffraction pattern that she saw. And Watson and Crick managed to get a look at this data. And it's a little complicated how that happened, but Crick realized almost right away that there were two strands running in opposite directions.
So he know knew it was 5 to 3 in one direction and 5 to 3 in the other direction like that. So you might have thought they were home-free, but no. They wrote it up and they were ready to submit the paper. And they gave a presentation to their colleagues at the lab in Cambridge. And they were shot down. And one of the key things was they learned the chemical fact that most of the textbooks were wrong at that time in the way that they depicted the structure of guanine.
If you look in your textbook, excuse me, here. So if you were to look in a textbook today you'd see guanine like this, but there is another way you could draw this. So this you may remember when we were talking about phosphoenolpyruvate that this is an enol form and this is a keto form.
And this is the way most of the textbooks were showing guanine at the time. So they were looking at the structure of guanine in textbooks. And if you were trying to work out schemes for putting bases together you can see what's going on up here would be very different.
And if we have a hydrogen here versus if we have an oxygen, if you're trying to say make hydrogen bonds at that particular position, I think all of you understand hydrogen bonds well enough to see how that would throw you off.
So once that insight came, once they learned that then the rest of the structure came pretty fast. And there's a movie about this. One of the nice things in it was sort of trying to recreate the experience where I think it was Watson who was shuffling these base pairs around.
And he suddenly realized that you could set up base pairs with A and T and with G and C, and when you looked at them you could see they were geometrically exactly the same shape. You could just take the shape of the G and C pair and lay it right down on the A and T pair. And then you could see how you could build either a G-C or an A-T pair into the repeating structure of this DNA and it would be compatible. So they built a model and they thought, we can just hit the lights for a second here maybe.
I just want you to see what that first model looked like. It looks like something you could hack together in a chemistry lab. They had the bases cut out of metal. And you can see just, you know, here the retort sort of stands using chemistry and various clamps that you would use for clamping a flask or something if you're doing a chemical lab.
That's the stuff that they were using to put the model together. And they published then a paper in Nature that told about this result. That's the entire paper reporting the structure of DNA. And maybe you can see there's a little hand-drawn double helix right there that captures the elements. That is the paper, and that was in the journal Nature.
And it had in it, right near the end, one of the coyest sentences in the scientific literature. They didn't want to go into all the details that if you had an A paired with G and G paired with a C and you pulled them apart then you could replicate the molecule by redoing it. Cold Spring Harbor is on Long Island.
It's been one of the Meccas for molecule biology since the s. They have a famous symposium once a year. The topic changes every year and rarely repeats. And it was at one of those symposia -- This was the year that they discovered the structure of DNA. And there was Watson. So two years ago they had another meeting, a special meeting just exactly this time of year.
It was in February within a couple of days of right now. So I gave this lecture and I showed the student in the class that this year, I said here's a picture of Jim Watson displaying the structure. They're having a meeting 50 years later in And I'm going down there. I'm asked to give a talk.
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