Biology: Chargaff, Franklin, Wilkins: DNA Begins

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Well it's finally been demonstrated. DNA is the genetic material. We know that. But what's DNA. You see now in the early 1950s, things were going to get interesting, because finally Hershey and Chase, without a doubt, put the protein-DNA debate to rest. But now the race was on to what is DNA? Now remember there are four things you need if you're going to be a genetic material. Number one you've got to be an information carrier. The genetic material must carry information. Number two- it's got to be capable of replicating. You know, cells divide. Cells make perfect replicas of each other.
This third one is kind of interesting. DNA or the genetic material has to have a way of running cell machinery. If you think about it, this created a real problem, because DNA is in the nucleus, and the cell machinery is outside the nucleus. So how did DNA run the cell if it was in the nucleus. Now maybe, people started to think, maybe proteins must run the cell machinery, because we've got to give protein some credit somewhere. And maybe DNA must be responsible somehow for those proteins, because remember Beadle and Tatum, the genetic material has something to do with making enzymes. Genetic material linked to enzymes. On the one hand it could have been enzymes. But if it isn't enzymes, one gene one enzyme, one gene one enzyme, one gene makes enzymes. Aha, maybe these genes must make proteins. And then the last thing is somehow we have to be able to explain the idea of mutation, the idea that change happens in the genetic material.
Well the race was on. So we're going to say genes make proteins, but how do they do that? How could something that is so simple, just something that is made out of adenine, guanine, cytosine and thiamin be the genetic material. Maybe we better review that for just a second and take a look at what we know of DNA at this point.
DNA, when it breaks down chemically, if you take the DNA, in 1950s I'm talking about, and break it down chemically, you find that it's composed of these things called nucleotides. And nucleotides were relatively simple, which is why everybody ignored DNA. Nucleotides consisted of a phosphate group that was hooked to a pentose, a sugar. There were two different kinds of nucleotides. There were deoxyribonucleotides. Deoxyribonucleotides were missing an oxygen here. Thus they were deoxyribonucleotides. Ribonucleotides had it. This sugar is ribose. And the only way that nucleotides differed, one from the other, this AGCT thing, was this base right here. It was called the nitrogenous base. And that nitrogenous base could be A or G or C or T. And it turns out that nucleotides or nucleic acids, DNA and RNA, must somehow be a polymer of these things. And the key was, now that they knew that this was the genetic material, how were they polymerized? What kind of polymerization did they use?
I want to go to 1950. And you know what, this guy's work really wasn't recognized until after everything fell into place. It was one of those things that, gee, maybe it would have shortened things by a year or two if people had been aware of it. His name is Erwin Chargaff, and now his work is well known. Chargaff really kind of broke two stories about DNA. Number one, the first thing he showed was that--he studied the ratios of the nucleotides. And current knowledge at that point suggested that in a given cell there'd be about 25% A, 25% T, 25% G and 25% C, give or take a little bit. Well the first thing he found out was that that isn't true. He found out, for example, that some organisms have different amounts of A than others. So he found diversity from organism to organism, from cell to cell. So for example, a mammal might have 42% of its DNA was C and G, and 58% was A and T, whereas a bacteria would have a different percent. That was good, but this was better.
What he found out secondly was that the amounts always equaled one another when you compared C to G, and when you compared A to T. Watch this. We'll use mammals as an example. He found out most mammals have the following ratio. Of all of your DNA, he found out that about 21%--in mammals now, because it was different in fruit flies. It was different in slugs. He found out that 21% of the DNA in your cells was C. 21% was G. He then found out that 29% was A, and 29% was T. A equals T. G equals C. There's the same amount of A as T, and the same amount of G as C. Isn't that interesting. What's it mean? I don't know, but it's very interesting stuff. Somebody was eventually going to figure out the meaning of that, which brings us to the work of Franklin and Wilkins.
Again, early 1950s, and what did they do? Well I have to explain something to you, a process called x-ray crystallography. And we have to figure out what x-ray crystallography does. If I have a crystal of a substance and I want to figure out exactly what it is, here's what I have to do. I have to take x-rays. Here's my crystal of that substance. To figure out its structure, I will take an x-ray beam, and I will beam it at that. And I will beam it at varying angles. So I will beam it so that it comes straight on. I'll change it by about two degrees, and I'll bring the beam on a slightly inclined angle, and it'll go through like this. And then I'll change the direction still again, and I'll bring it through like this. And what I will do is I will expose on this side of the crystal a photographic plate. And we go right through. It starts and goes right through the crystalline material. What that does is that exposes a kind of a negative energy on the plate. I've worked with x-ray crystallography. It's very complex. The good news is all I had to worry about was a computer. The computer said, "Oh, this is such and such a thing," because of the way that the beams bent as they passed through the crystal. And that's the key. When the x-ray beam goes through, and it passes near an atom, there are gravitational electromagnetic forces that cause that beam to bend. So in the bending, you get an exposure on that plate. Franklin and Wilkins worked with crystallized DNA. And in working with crystallized DNA, they got a picture of DNA exposed. And here it is. Is that clear or what? Well if you can read this picture, you're good. But you know, that's the thing about this whole idea of x-ray crystallography. By using mathematical formulas, you can actually predict some things from a picture like this.
Now when they did some measurements, numbers came up repeatedly throughout this thing. And you can kind of get the idea that you're looking into a circular, you're looking kind of like--here's what they thought. They thought they were looking down into some kind of helical molecule, because of this circular formation that you kind of see outlined on this picture. But when they did some measurements, some numbers came up. And the numbers were 2.0 nanometers, 0.34 nanometers, and 3.4 nanometers. What those numbers meant was up to the interpretation of the biochemists and the x-ray crystallographers. But it was repeating.
They also felt that by looking at this thing, that it was a helical molecule. Well why have so few of you heard of Franklin and Wilkins? Well it's because Franklin and Wilkins had a visitor. There was this young American who was visiting, at Cambridge University, a friend of his. His name was Crick. The American visiting him, James Watson. One day James Watson went to visit the lab of Wilkins and saw this picture, and looked at it and said, "I think I've got it." And back he went to Crick. And the story started to unfold.
Molecular Genetics
Discovering DNA
Chargaff and Franklin and Wilkins: The DNA Story Begins Page [1 of 2]