(epic music) - John Cairns sat on the telephone, in a very excited voice. He had just read Mendel's papers. And you know, they are the most beautiful
experiments in biology. And I gasped! And I said, "John, John,
you can't say that." You said, "The Meselson-Stahl experiment, was the most beautiful
experiment in biology." "Oh, did I? Well, I was wrong." (both laugh) (epic music) - Watson and Crick
didn't make a discovery. They proposed a model. There are those who believe
this model must be true, because it was so beautiful. And there were those who
believed it must be wrong, because biology is complicated, and this model is too simple to be right. Would you say? - Exactly, yes.
- Yeah. But there was no
experiment or proof of it. - They had a model which
made a distinct prediction, about how DNA replicates, and it needed to be tested. And it's fun to test the hypothesis. We agreed that we were
going to work together, to figure out, whether
or not it was right. (epic music) - When Frank and I, showed semiconservative replication. It wasn't just a model, it was something real like that. - Thereafter our experiment, it was now widely accepted that their model, Watson-Crick model is right. So it became the building block. You might say for all of biology. - Yeah. ( epic music) From very early childhood, I mean, practically infancy. I loved science. I loved to put wires together. To make little radios, which I could put under my pillow, so my parents wouldn't know, that I was listening
to them all night long. And then, I was very interested to know, what makes life work. And, there had been I think, in the house, maybe even in my bedroom, that painting by Michelangelo, of God, up high and Adam below. And they're touching fingers. I don't know if there is a spark. I don't think there's
a spark in the picture. But I'm not sure. But to me that meant that,
life is somehow electrical. That God is providing
life through a spark. And for some reason, that made me interested
in electrochemistry. - Unlike Matthew, I had no particularly
strong interest in science as a youth. What was understood, that when I graduated from high school, I would apply to the Naval Academy. That's what my mother had in mind, because she thought I would
look good in dress whites. But then of course,
World War II broke out. So that plan changed fast, and she decided I should
just go to college. I think I was just too young, to understand the courses in humanities. I hadn't had enough life experience, to get a grip on the questions, they were even thinking about. Science on the other hand was concrete. Children can grasp science. And among the sciences, biology was the most appealing. There, the fun was, that you could figure out puzzles. That is, there was a rational, concrete, quantitative explanation, for what you saw. You could reason backwards, as to what must be going on. And that intrigued me enough, to know that genetics was
something perhaps I could do. (epic music) - I had the great good luck, to become Linus Pauling's
last graduate student. His daughter was having a
party at their swimming pool. And I'm in the water, and Pauling comes out, the world's greatest chemist, and he's, I'm all naked and
practically wore a bathing suit. And he's all dressed up with his jacket, and a vest, and a neck tie. And he looked down at me, "Well, Matt, what are
you gonna do next year?" And I had already signed up to go to the, committee on mathematical biophysics. And Linus looked down at me and he said, "But Matt, that's a lot of baloney, come be my graduate student." And so if I hadn't taken his course, on the nature of the chemical bond, I would have had a very different life. I wouldn't have met Frank. I wouldn't be sitting here. That's for sure. At the end of my PhD exam, as we were walking out
of the little exam room, Linus Pauling turned to me and he said, "Matt you're very lucky, you're entering this field
just at the right moment." - Yeah. - "At the very beginning." - Yeah. (epic music) - The first year of my, being a graduate student at Caltech, I wanted to get into biology. I was a chemist, and I thought the way to do that, would be to study molecular structure. The only person who
was looking at biology, from that point of view, other than Linus Pauling himself, was Max Delbruck. He had a fearsome reputation. (Frank giggles) Nevertheless, I gathered my courage went to see him. He's not a fearsome
creature at all, really. And the first thing he said was, "What do you about these two
papers from Watson and Crick?" I said, "I'd never heard of them." I was still in the dark ages. And he yelled at me. He said, "Get out! And don't come back
till you've read them." (epic music) There were two separate
ideas, that came together. Crick's idea about how the base pairs, linked onto the chains, and Jim's idea about how the
base pairs were structured. So there are four different
building blocks of DNA; adenine, thymine, guanine, and cytosine. - The surfaces of the G and the C, are complimentary to each other. And at the A and T are
complimentary to each other, so that they can fit together, the way fingers would fit into a glove. And importantly, when they put G opposite C, the distance of the outside, was exactly the same, as if they put A opposite T. No other combination would
give such a regular structure. It was a gorgeous insight. And then, from that, they made a hypothesis, about how DNA is replicated. It involved, the two chains coming apart, and each one acting as a template, for the synthesis of the
new chain, on its surface. When it's all done, here
we have the two old chains, each one now, associated
with a brand new chain - What Watson and Crick proposed, was enormous stimulus to experimentation. - It was irresistibly beautiful. - Irresistibly beautiful. Jim Watson was at Caltech, the year after he and Francis
published their papers. And so I got a chance to
talk a lot with Jim then. And that coming summer,
he was going to go, and teach the physiology
course at Woods Hole. (epic music) - I was a graduate student
at Rochester at the time. My chairman of the department, who was also on my committee, said I had to take a foot
course in physiology. And I said, "The physiology
teacher here is a jerk. I'll be damned if I'll take his course." Well, send him to Woods Hole, to take the physiology course there. And by serendipity, Jim Watson happened to be there, with some kid named Meselson,
hanging along with him. We found that we had in
fact deep common interests. I realized, this is a guy
who's really very smart, and I can learn a lot from him. I remember a haze of beach parties, lectures that I slept through. - It was a kind of paradise. The most interesting people
in molecular biology, most of them were there. So that's how we met, and then it turns out, Frank is coming that very
September to Caltech. (indistinct) - No, a year from then, I would come. - Are you sure? - Yep! - Oh. - I still hadn't finished (indistinct) - So I had to wait for a whole
year before I saw you again? - That's right. He said, "When you get to Caltech, we'll test Jim's idea. What do you think about
testing Jim's idea, of how DNA replicates?" And then he explained that to me. I'd already heard about it. And he explained it to me. And absolutely, I committed totally. - And then when Frank finally got there, and I wanted to start right
away, he forbade it, why? He said it would be bad for my character, to not complete my x-ray crystallography, before starting something new. This is, tells you a lot
about Frank's character. (epic music) With the Watson-Crick model, the underlying question of course was, was that really the right mechanism? - The famous Max Delbruck
said no, no, no, no. That model can't be right, and he proposed a different model. As Delbruck put it forth, breaks are introduced in
the parental molecule, as it's being replicated, and then carefully sealed
up in certain ways. Others proposed one in which, the original DNA molecule stays intact, and the new DNA molecule
is made of all new DNA. So there were three targets out there, that in principle could be distinguished, if you could trace the
fate of the old chains. What becomes of the two old chains? - So the one step led to the next, really. I mean the first idea
using density somehow, is not a very good idea yet, except it leads you to the next one. - Matt's idea from the very beginning, was that somehow, stable isotopes, could be used, that would be incorporated into the DNA, and impart upon the DNA,
a different density. - You grow bacteria, in a medium, which instead of having these, ordinaries isotope of nitrogen, N14, you can buy nitrogen 15, ammonium chloride, heavy kind. And if you grow the bacteria
for a number of generations, even be sure that essentially, all of the DNA, is labeled with the heavy nitrogen, good. Now, we suspend those cells, in a medium that's just as ordinary, not nitrogen 14, the light one. And now the question is, as the DNA molecules replicate, how will the heavy nitrogen, from those parent molecules, be distributed, amongst the daughter molecules, that are produced in
successive duplications? - Then some sensitive
method, for separating DNA, according to its density, would be devised. - I ran across an article
about the centrifugation, of cesium chloride solutions, to measure the molecular weight. - If the DNA was in there with the cesium, it would find its position
in the density gradient. If it was heavy DNA, it would tend to be down
near the bottom of the tube, where the cesium was concentrated, and the density was high. If the DNA was light DNA, native light isotopes, it would be higher up in the tube. (epic music) You could think about it this way. If you jumped into the Great Salt Lake, as we all know you float. You go right to the top. Because you are less
dense, than the water. But if you have the bathing
suit, with pockets in it, and you stuffed some lead
weights in your pockets, you'll sink down. 'Cause you're more dense than the water. Now, imagine that the salt, in the Great Salt Lake, is not uniformly distributed, but it's concentrated near the bottom, and rather less concentrated near the top. Now, if you put just the right number, of heavy weights in your pocket, you won't float because
you'll be too dense. You won't float at the top, and you won't go all
the way to the bottom, because you're not dense enough. You'll instead come to rest somewhere, halfway between the top and the bottom. You will have found your
place in that gradient. And that's the very basis, by which the experiment finally worked, and worked so beautifully. - And then it was just a question, of looking in the centrifuge, while it's running, and when it reaches equilibrium. To see where the heavy and light DNA are. - All of the makings were there then, to do the experiment itself. It was hard to say the experiment, was going to give an answer. - Driving it all, was the fact that Frank
wanted to know how life works. - Yeah. Um lets... Yeah, well, how did
that drove it all, but, - Each person, is trying to come up
with something as a gift, to the other guy. - That is true. - I think. - That's true. - So this becomes a very
connected relationship, 'cause the next day you wanna
have something to offer. - Matt was ready to step
out into an area of, oh pretty heavily unchartered. To answer an important question. And the pieces had to be
built as he went along. (epic music) - The prediction of the
Watson and Crick model, that the two parent chains come apart, each one makes a new daughter molecule, and that's replication. So that would predict, that after exactly generation, when everything has doubled,
in the bacterial culture, that you'd find the DNA molecules
all have one old strand, which is labeled heavy. And one new strand, which is labeled light. And therefore their density, should be halfway between
fully heavy and fully light. That would be the
prediction for what you see, at exactly one generation. - What do you predict to
see for the next generation? Well, each molecule would
again, separate its chains, one of which is heavy. the other of which is light, and the only growth medium available, is light growth medium. Then the light chain, would make another light
chain to go with it, a compliment. The heavy chain, would make another, a light chain to go with it. So after two generations, you have DNA, half of which is half heavy. And the other half of which is all light. (epic music) And fantastically, that's exactly the result
that one could see. (epic music) In order to say that, the Watson-Crick model, fits the data very well, but the other two models do not, we have to see what they predict. Start with the dispersive model. After one generation, the two molecules resulting, would indeed be half heavy, but in the next generation, there would be a subsequent
dispersion of the label. So you'd be getting molecules that were, three quarters light, and one quarter heavy. And in each generation, the molecules would get
lighter and lighter. The fully conservative
model simply imagined, that duplex DNA, fully heavy now, somehow, created the appearance, of a fully light duplex molecule, in which both chains
are made of light DNA. And most of the times when you
get an experimental result, it doesn't speak to you with such clarity. - Yeah. - These pictures of the DNA bands, interpreted themselves. (epic music) - It felt like a- - [Frank] Of course. - Supernatural. It felt like you were
in touch with the gods, or something like that. - I remember I presented this result, that summer, earlier in the summer, in France at a phage meeting. We completed the photographs, of the density gradient bindings. And at the end of it, I stopped, and there was total silence. And somebody said, "Well, that's it." (both chuckling) (epic music) - At the intellectual freedom at Caltech, we could do whatever we wanted. It was very unusual for such young guys, to do such an important
experiment so suddenly, whereas before that, like Max would be talking with Sinsheimer, about the genetic code. And before we did our
experiment, I was definitely not, well at least I felt like, I wasn't supposed to be
at those discussions. But afterwards, I could be a full member. (both chuckling) We had this wonderful house, big house, across the street from the lab, and, our roommates, we all, we talked about these experiments, at almost every dinner. So we had this wonderful
intellectual atmosphere. John Drake, Howard Temin. Why are you frowning? - He told the dirtiest
jokes I've ever heard. - No, that was Roger Milkman. He told even dirtier jokes. - Well, okay.
- You're right then. - They held positions one and two. - That's true, that's true, that's true. So it was a very lively, intense, friendly atmosphere. - It was lively enough, and conveniently located
enough that over time, we had visits from William O. Douglas. - [Matt] Judge Douglas. - [Frank] Judge Douglas,
of the Supreme court. - And the Arizonian. Here is Dick Feinman, probably one of the world's greatest, physicist at that time, or maybe ever. Palled around with us, he came over to our big house, played his drums, down,
sat down on the floor, played the drums. I'm just a graduate student, and he's the world's greatest physicist? But that's what it was like. It was a very friendly wide open place. Frank and I are very lucky. The way I think of it
is that there's a river, which is the period of time, when the fundamental things, the structure of DNA, how replication happens, the genetic code. And then when these solves,
these problems are solved, there are lots of little rivulets. The river divides into
thousands of branches, using these fundamental
insights into how life works, and applying them to specific questions. Questions of disease,
et cetera, et cetera. So, to me, with some exceptions, this was the really interesting time, when it was still a big river. - Also, now that you can cut this out. But also the Meselson's, Matt's parents were kind enough to
keep the liquor cabinet fully stocked at all times. (epic Music) My throat is a little bit- - I had a cough drop so- - Suffering. - Try to (indistinct) drop
of non-alcoholic beer. - No, no, no, no, no. - I require a margarita. I've worked for the CIA, with the giant squids and all that. I vaporized many people, including many of your friends. A big black beard, and blew out some of his pipe smoke, and still holding his pipe
stem in his teeth, he said, "Oh man! History is just what people think it was." (both laugh)
