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ERIC LANDER: Good morning. Good morning. So last time, we ran into a problem. We had Mendel, my hero Mendel, this MIT-like mathematical, physical monk, had developed this gorgeous theory of particles of inheritance. He didn't use the word "gene" yet. Gene doesn't get invented for much longer. For every trait, you had two such particles. You gave one to your offspring. Each of the parents gave one to their offspring. And that's how each offspring gets two of them. That choice of which of the two alleles to transmit to your offspring is a random draw. And that explains beautifully, for example, the 3-to-1 segregation pattern that Mendel saw-- gorgeous. We put that model, which was an ex post facto model, a model made after the data were available, to a test. You guys insisted we had to test it before you would publish it. And it holds up pretty well, making pretty surprising predictions that you would otherwise not have ever expected. Like amongst that...

ERIC LANDER: And so the issue became how does DNA replication work. And so I'm about to go into it. Now, I'm going to note we're going to be starting this DNA goes to RNA, goes to protein, and DNA goes to itself. DNA is replicated. It makes RNA. The RNA is used to make protein. This will be what we'll be talking about today and tomorrow. So the first step of that is, how does DNA give rise to more DNA? Well, how do you find an enzyme? How do you do biochemistry? What do you do? AUDIENCE: Assays. ERIC LANDER: Assay. So you've got to grind up the cell. I got to choose a cell in which I'm likely to find an enzyme, grind it up, break it up into different fractions, and test each fraction. That's all biochemists do, right? So what cell might have the enzyme we're looking for? What cells might be able to copy DNA? How about all cells? So let's use a simple cell. What's a simple cell? Let's use bacteria. So we'll take some bacteria...

ERIC LANDER: That worked. Let's do it again. Now, number 2. I would like to clone not the Arg1 gene, but let's say the beta globin gene from human. So let's take human beta globin. I want to clone it. So human beta globin, hemoglobin, it's a tetromer. It has four parts. It's got an alpha, an alpha, a beta, and a beta. Four proteins come together in a protein tetromer. And it's got two alphas, two betas. The beta subunit of hemoglobin is encoded by the human beta globin gene. That's the nomenclature here. All right. Let's clone beta globin. Same deal. How are we going to do it? Any takers? What should we start with? Yes? AUDIENCE: Find a restriction enzyme? ERIC LANDER: Find a restriction enzyme. I'll go to catalogue and try EcoRI today. OK? Now what? AUDIENCE: Add it to a bunch of [INAUDIBLE]. ERIC LANDER: So I'm going to start with human DNA? AUDIENCE: Yes. ERIC LANDER: Yes is a good answer. Yes. I'm going to start with human D...

ERIC LANDER: So, now what I'd like to do is turn to variations on the theme. One of the best ways to understand what's going on with DNA goes to RNA goes to protein is to consider how it works in different organisms. And the organisms we'll consider are eukaryotes, like you; prokaryotes, like a bacterium; and viruses. And each does the same basic copying of nucleic acid to nucleic acid, transcription, and translation. But there are some pretty fascinating variations on the theme. So let's turn to those variations. Let's start with DNA replication. For eukaryotes, your genome are long, double-stranded DNA molecules, and they're linear. Long, linear, double stranded-- ds for double. I'll write it out-- double stranded DNA. You know this. And you've got a lot of it. The human, you actually have 23 pairs of chromosomes. And the total length of your DNA is about 3 times 10 to the ninth base pairs. So about 3 billion bases or so, typical chromoso...

ERIC LANDER: Good morning. Good morning. So we've been talking about recombinant DNA. And really what it does to our picture here-- function, gene, protein-- is for the first time take something that's a theoretical relationship and make it operational. Being able to go from a function like the ability to make your own arginine, to a specific gene, to a specific protein, and to be able to connect those up. In principle, by the time we're done with recombinant DNA, one should be able to go from any vertex of that triangle to any other vertex of that triangle. Given a function, find the genes. Given a gene, find the proteins. Given a protein, find the genes. Given a protein, find the function. That's really the goal of recombinant DNA is to be able to start at any vertex and reach any other vertex of that triangle. We're not there yet. But we will be in the next couple of days, to the point where we can move freely about this whole picture. So we've ...