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The discovery of the double helix structure of DNA

Video transcript

- [Voiceover] In 1865, Mendel, often considered the father of modern genetics, comes up with a structured way of thinking about these inheritable factors, which we now call "genes." And then as we go into the early 1900's, his work was rediscovered, and people started to say, "Okay, we see how some "of these traits get passed on in these "somewhat predictable ways, we can put "some structure around it, but what is "the actual biological mechanism for that? "How are these traits encoded at a cellular, "or at a molecular level?" And so, in 1902, and we talked about this in a previous video, Boveri and Sutton come up with the Chromosome Theory, based on seeing how chromosomes separate and pair during cell division, and saying, "Hey, those seem to map up quite well "to what Mendel described by these heritable factors." Then we start having a lot more evidence for this. Morgan is able to show that a mutant eye color trait seems to be passed on in a way that shows that it is on the X sex chromosome, and he and his team start doing a lot more work, especially with fruit flies, to show that, "Hey, chromosomes are the basis "for where these heritable factors are." But then even within the chromosomes, people weren't sure, chromosomes were made up of protein, made up of DNA, what was the molecule or the set of molecules that actually encoded for these heritable traits? And at first, most of the weight was on the protein side, because proteins were these complex molecules that had all of this variety that seemed that it could code for these heritable traits, while DNA, at least early on, seemed like a kind of boring molecule, people assumed that there wasn't a lot of diversity in DNA. They assumed that even if you go from one species to another that the DNA molecule was fundamentally the same. So early on, people actually were on the side more of the proteins. But then more and more evidence came on DNA's side, you had Griffith's experiment, where he was able to show, "Hey, I could take "this heat-killed bacteria, but if I mix it "with some other living bacteria that somehow "there's some transformation principle "that transforms the living bacteria into the "type of species that I had heat-killed." And you go to 1944 and Avery, McCarty, and MacLeod are able to show some pretty good evidence that the actual principle, the thing that was left in that heat-killed bacteria, was probably DNA. And then we get even more conclusive evidence with the experiments of Hershey and Chase and we have a whole video on this. Where they say, "Hey what is it that "viruses inject into bacteria to hijack "their genetic system?" And they say, "Hey, it's not proteins! "It is DNA that does this." So they provide much more conclusive evidence on the side of DNA. But even at that point, we as a community, as a civilization, still didn't know what the actual structure of DNA was. We also did not know, how did that structure actually code for all of these heritable factors? And the work culminates with Watson and Crick, but it was dependent on all of the people I mentioned, and more. And one person who should get special credit for, one, getting a little bit more evidence on the side of DNA and helping Watson and Crick, actually there's several people. But, in particular, Chargaff, and Rosalind Franklin, and Rosalind Franklin in particular probably does not get as much credit as she deserves. Chargaff's the one that showed, DNA actually is more interesting than people appreciated. He noticed that the frequencies of the nitrogenous bases of adenine, guanine, cytosine, and thymine in DNA varies across species. And, something that's somehow coding for what makes a species a species, well, it would have to vary across species so that makes DNA interesting. And then the other thing that he noticed, and this was key for Watson and Crick's work, is that the frequency of guanine is equal to the frequency of cytosine in DNA, and the frequency of adenine is equal to the frequency of thymine in DNA. And so it's a clue that these somehow are associated with each other, they somehow pair with each other. And so we get to the early '50's. We had all of this evidence that DNA is the molecular basis, you have Chargaff with his rules called Chargaff's Rules, and then you have Rosalind Franklin, and she's imaging diffraction patterns from X-rays beamed into crystals of DNA. So what I mean by crystal of DNA, a crystal is taking a bunch of molecules and arranging them in a regular pattern. So a crystal of DNA, that's one DNA molecule, then you have another DNA molecule, and then you have another DNA molecule, and then you beam X-rays at them, and X-rays are key because the wavelength of an X-ray is small enough to capture the features at an atomic level. So you beam X-rays and then the X-rays diffract. And then you capture the pattern of that diffraction. And then depending on the structures in the actual molecules you'll have different diffraction patterns. And Franklin's famous diffraction pattern is shown right over here, and when she immediately saw this, it had some of the telltale cues for a helical structure. Now, I wouldn't read too much into this if you're not an expert reader of X-ray diffraction patterns, this isn't a direct image of a DNA molecule, but they knew, she already knew and in fact people in this community already knew that this X pattern was a telltale sign for a helical structure of some kind, and then they were also able to look at the other clues here to think about, "What's the spacing between different molecules?" And even the spacing between the different turns of the helix structure. Now once again, this diffraction pattern is not a direct image. It's a very well-develped expertise to backwards map how things will diffract into the thing that actually caused the diffraction. And they would take it from multiple different angles to get a better understanding of it and actually today, you have computers doing this that could take a diffraction pattern and start to construct what the electron clouds of what the actual molecule looks like. So Franklin, this was painstaking work, and she already had a sense, she knew it was a helical structure but she was waiting to get a little bit more evidence before she published her work. Now at the same time, you have Watson and Crick here, who were trying to solve the structure. And they got a hold of Franklin's work with the help of Maurice Wilkins here, who Franklin worked with. And they were able to establish that it wasn't a single helix, but it was a double helix. And you actually had these base pairs forming the rungs of the double helix, and that was really interesting because that showed how DNA could replicate itself, how it could contain actual information. And we go into much much more depth in two future videos. Now the sad part about this story is, Wilkins, Watson, and Crick went on to win a Nobel prize, Franklin unfortunately died very young and you're not allowed to receive a Nobel prize if you've passed away. So she's very deserving of it. This work, which a lot of people consider to be one of the biggest discoveries in science, was based on what she did. Arguably, had Watson and Crick not had access to her work, they would not have been able to figure it out, and if she'd just stuck to what she was doing without other people having accessed her work, she might have been able to get to that same conclusion, so she is one of the people who, sometimes, the history of science overlooks. But this isn't to not give credit to Watson and Crick either, there were still a lot of very powerful intuitive leaps that they had to make to come up with this double helix structure, this anti-parallel double helix structure where they go in opposite directions, but they bridge with these nitrogenous bases pairing with each other. And this is a big, big, big, big deal. Throughout most of human history, we knew that traits were passed on but traits seemed like this magical mystical thing. "I know my laugh is like my dad's, "but how is that actually encoded in my DNA?" And now, we're able to see that a lot of what we consider about ourselves to be us, is encoded in these molecules and encoded in these base pairs, so it's beautiful, it's incredible, it's shedding light on one of the biggest mysteries of what makes humans, actually all life, life.