9UNP0195SD_Tom _Zinnen_WordPress

- Hi, welcome everybody to Wednesday Nite at the Lab. I'm Tom Zinnen. I work here at UW-Madison at the Biotechnology Center and for UW Extension Cooperative Extension. And on behalf of the Wisconsin Alumni Association, welcome to Wednesday Nite at the Lab. We do this every Wednesday night, 50 times a year. I get to be the presenter tonight, in part because we're moved out of our normal meeting place in the auditorium. So tonight, we're going to do a series of hands-on activities and metaphors and experiments to help get a better grip and feel for DNA. So the first thing that we'll start with is the whole idea of a metaphor and an analogy. And we do that a lot because one way to look at this stuff is through these models, but another way is through ways of thinking about things. We're going to start with the first puzzle. 

And the first puzzle is, I'll pass these around. And would everybody get a tube of DNA. And then look at this tube of DNA and tell me, what do you think is really in here. When everybody has one of these, I want you to look at the label. Tell me, what does the label say it is? A sample of DNA. Please have a conversation with the people you're sitting with. Please tell me what's really in this tube. 
(inaudible)

 So what I would like you to do is think about how you frame a question. 

You can frame this question narrowly. What do you think is really in the tube? Or, we can frame it more broadly. How many different things can you imagine this stuff might be? How you frame your question can speed or impede your research and your investigation. So what are some things that this could be besides DNA? Dryer lint. As opposed to wetter lint. It could be DNA. What else are some things it could be? 

String. It could be a string of DNA. 

- Toilet paper. 

- New or used? 
(laughter)

 We'll say new. What else does it look like? Plastic, okay. Other things? Very good, dental floss. 

Other stuff it might look like? Thread. We can make more of these suggestions. This is where we want to be able to get across the idea, how you frame your question. Do you frame it narrowly or do you frame it broadly. Speed or impede your investigation. What's number two up there? Nothing, so far. Whenever you have these kinds of ideas, the first is of course, it's DNA. That's what the label says. 

Whenever you have an idea, or testable idea, the fancy word for that is hypothesis. How many hypotheses does a good scientist usually work with? How many are they supposed to work with? How many have they been taught that they're supposed to work with? Most people are taught one. And I would like to think from now on, maybe we should work with at least two. In this case, it's either DNA or it's not DNA. And the fancy word for that is the null hypothesis. So if you taken a course in probability or statistics, and you've done hypothesis testing, you test your hypothesis against its null. This is a very big step in sophistication for many people. 

Of the two first ideas, it's either DNA or not DNA, which one do you treat more fairly? It's a trick question. You treat them fairly, you treat them equally. And then if you have only two ideas, is that as powerful as having three, four or five or six. Two buildings down from here, the building is named for Thomas Chamberlin. He was president here from 1887 to 1892. And in 1890, he wrote a very famous essay, called the Method of Multiple Working Hypotheses. And he said if you have only one hypothesis, what will you do to it? You'll coddle it and cradle it, and take possession of it, and protect it. But if you have a family of hypotheses, it's like having a bunch of kids. 

You try to treat them all the same and not show any preference. It's a very powerful idea, to try to have many possible ideas, and not just one. You'll often hear scientists say, here's my hypothesis, and I'm going to try to prove it. It might be better to say, here are some hypotheses, and here's how we can test them. So how do we go about testing, whether this is DNA or whether it might not be DNA, whether it might be cotton and string? I'll tell you one factoid, and then you can have a conversation about how you're going to test this. Here's the factoid. DNA dissolves in water. So go ahead and have a conversation about how you're going to test, is this DNA or is it not DNA, might it be cotton string. 
(all talking indistinctly)

 Ah, yes. So why don't you just take-- If DNA dissolves in water, why don't you just take this off and pour some water in here. Because if it is DNA, it'll dissolve. Then how much of this white, fuzzy stuff will you have left? None. And then how many more tests can you run? None. And how many total tests will you have been able to run? One. Is that a very good number of tests to run? 

No, so what can you do? What can your strategy be? Pull a chunk off, very good. Now you have invented the idea of taking a sample, or even better yet, a subsample. Please pop the top on that. Put it in your hand and break it into two pieces. Now, if you break it into two pieces, do you have to break it into two equal pieces? Do you even want to break it into two equal pieces? I think I would break it into two pieces. But one, an itty bitty piece, and the other a great big piece. 

And just put the itty bitty piece down on your table top. And put the rest back in your tube. Put the lid back on real tight. And take it home as a souvenir. Now, where are you going to get some wa-wa, water? Right here on the tray. And you'll notice there's little cups like this. So if you pour some water into your cup, that'll make it easier to do. Because what I would like you to do, is to use your digitus aquarius, and use your finger. But before you do that-- 
(laughter)

 Before you do that, I would like you to do some Promethean thinking. Who was Prometheus, by the way? He was a Greek God. And what was he famous for? He brought fire to humans. And that pissed off Zeus. And what did Zeus have done to Prometheus? He had him chained to a rock, kind of like our foreign policy. 
(laughter)

 And every day, what came? A big bird came and ate out his liver. And every night, what grew back? His liver. He must be at least part from Wisconsin. What does that tell you about what ancient Greeks knew about regenerative medicine? The human liver is one of the few human organs that can actually regenerate. Prometheus is famous for giving great gifts to humanity. One was fire. The other one was, what's at the bottom of Pandora's Box? 

Hope. And the third one was his namesake. And is namesake literally means knowledge of forethought. Plan ahead. Anticipate. He had a brother named Epimetheus. And that meant knowledge after the fact. Monday morning quarterbacking. I would like you to do some Promethean thinking. Because if you take your finger and get a drop of wa-wa on it, and rub-a-dub that little piece of DNA stuff, and it does dissolve, there are at least two possibilities. 

One is that is DNA, and that is water. The other is that's cotton string, and we've got some weird water here in Madison. So how can you know, how can you show? Better yet, how can you test whether in fact this water doesn't dissolve cotton? What do you need? You need a little cotton string. Where are you going to get some cotton? Take your right hand and repeat after me. I'm now going to dive into my pants pockets and get out some lint. Oh, no, there's a microphone hanging there. 

Okay, so if today's a lintful day for you, great. If it's not, you can get some of these. Okay, then peel some off. And if you've got a big, honkin' gob of lint, and a little bitty piece of DNA, is that fair? No. Who's in charge of making the experiment fair? And who's in charge of doing it fairly. And who's in charge of interpreting it fairly? So go ahead and get yourself a little bit of cotton, about the same amount as the little bit of DNA you have. And a little drop of water at one finger, a little drop of water at the other. 

And rub the two of them. Keep them a couple inches apart. And see what happens. What are you finding when you rub the cotton? Does it get wet? Does it dissolve? What are you finding when you rub the stuff that came out of the DNA tube? Does it dissolve? Yeah, it gets kind of gooey-gluey. It's kind of slimy. 

So did anybody find that their stuff from the DNA tube did not dissolve? Did anybody find that the cotton string did dissolve? Let's do the logical syllogism. DNA dissolves in water. That's a true statement. This stuff dissolves in water. That's a true statement. Therefore, what can you conclude? 
(inaudible)

 Let's try that again. 

This stuff dissolves in water. Excuse me, DNA dissolves in water. This stuff dissolves in water. Therefore, this stuff is? It's just water soluble stuff. Have we proven that it's DNA? No. Let's try a real syllogism. Can you have two true statements and still get a false statement out of it? Yeah, you've got to be real careful in how you structure your syllogism. 

Thank you for the word, there. Next, let's try this syllogism. Cotton does not dissolve in water. This stuff does dissolve in water. Therefore this stuff is not cotton. Have we proven that this is DNA? No. On the other hand, have we disproven that it's cotton? Is there a difference between proof and disproof? How many pieces of evidence does it take to disprove something? 

One. How many pieces of evidence will it take to prove it? A lot. As a matter of fact, I don't know that I could ever prove to you that this is DNA, prove empirically to you. The best that I could do, after all these experiments, all these different assays, the best I could conclude is so far this stuff is indistinguishable from DNA. Is there a difference between saying this stuff is DNA and saying this stuff is indistinguishable from DNA? Is there a difference between making statements about nature and making statements about our best understanding of nature? So the DNA tube is a parable. But it's also a paradox. Because when you pick this up, most people in the United States, in fourth grade or further, when they look at, even though it's labeled as a sample of DNA from a moderately reputable source, what do most people say. 

This isn't DNA. It looks like that string. Why is that? And I think what's going on is most people have seen the NOVA special where they've got a little thing, a model of a double stranded helix, DNA. The Walter Cronkite voice comes on and says, "And here's a picture of double stranded DNA." But you'll never see this because DNA is too small to be seen. Or better yet, a single molecule of DNA is too small to be seen. What do people remember, even if you're told a single molecule of DNA is too small to be seen? What does your memory tend to remember? DNA is too small to be seen. 

We kind of lop that part off. So let's resolve this. Can you see water? Sure. Can you see an individual molecule of water? No. Can you see an individual molecule of DNA? No, but if you get a bunch of them together, might you be able to see it? Yeah. And this is also a good example of this parable of the DNA tube. 

It's a good example that learning is one of the big things about education, whether you're in kindergarten or in college. But there's another big aspect of learning. And that is unlearning. And in science, sometimes the toughest part is not learning something new, but it's unlearning something that we've believed for a long time. If you're working with concrete, when's it real easy to work with? When it's wet, when it's sliding down the slide. 24 hours later, not so easy to work with. So that's another parable for this. It's pretty easy to work with a new idea, but once it gets set, it gets hard to think about it as something you might want to continue to test. What's in the DNA tube? 

This is the little jar that it comes from. And it says Deoxyribonucleic acid, sodium salt, from salmon testes. A little boy salmon gave it up for you. So, we started with a parable and a paradox, because I think one of the funnest things to do is to start with a puzzle, start with something intriguing, something that's puzzling. And that's why we start with the DNA tube. You don't learn very much about DNA from the DNA tube. You only learn that it's white fuzzy stuff, or can be, and it dissolves in water. But it's a good parable for science as an experience in coding the unknown through experimentation. So now I'd like to start with some of the other analogies here. In contrast to DNA as a blueprint, which most people have heard before, I would like you to think of DNA as a ribbon. 

As a ribbon. And here's why. Because that's what it looks like. And if you take a circular ribbon and cut it, how many pieces do you get? One. So when you look at that little guy here, DNA, as a ribbon, keep in mind this is why cutting and splicing is possible with DNA, since the early 1970s, as a technology. Because DNA is a ribbon, and when you cut a it, if it's a circle, you open it up. And if it's a line and you cut it, you get it into two pieces. Is it possible to take a little bitty piece and insert it into a bigger piece? That's a big idea. 

It's not really so easy to do that cutting and pasting stuff with a blueprint, compared to a ribbon. The next thing is DNA is kind of like a recipe card. How many recipe cards would there be if we have about 30,000 genes? We'd have about 30,000 recipe cards. My dad is a nice conservative republican, and he shoots up every day. Why does he take injected drugs every day? Because he's got adult onset diabetes. And he gives me his little jars that are leftover. And in that is human insulin. But it's not from humans, it's from bacteria. 

How do you get human insulin from bacteria? It's possible using genetic engineering and recombinant DNA technology to take a copy of a gene from one organism and give it to another. Let's look at this like a genetic recipe card. Let's say there's about 30,000 genetic recipe cards in the human cell. What if you could find the genetic recipe card for the protein that's called human insulin? And if you could pull that recipe card out and make a copy of it, and then give it to the recipe box of a bacterium, what does that bacterium now have the genetic recipe card to make? 

- Insulin? 

- Human insulin. And if you do all this stuff in just the right way, you can start with that one bacterium and it'll divide from one to two, two to four, four to eight, eight to 16, 16 to 32. And overnight, and after a while, you're going to have lots and lots. 

And all of them can have a copy for the gene for human insulin. So if you grow the stuff up in a big vat, you can actually have the bacteria making the human insulin. Before 1980, if you wanted human insulin, where did you have to get it from? A human. Could I borrow your pancreas, please? That doesn't work so well. And starting in the mid-'20s, when a couple folks up in Canada figured out how to get this from pancreases, we could get usable insulin from the pancreases of livestock. But starting in about 1980, it was possible to get human insulin by doing genetic engineering. And one way to look at that is to say, let's look at these genes as genetic recipe cards. If I can find them, I can make a copy. 

And if I can make a copy, I can give them to another organism. Then I can grow up lots of those bacteria in this case, and they can be my source of human insulin. Another way to look at DNA is DNA is like videotape. This is soon to be a dead medium. But it's a really great analogy right now. Have you ever run over one of these things and have it spill its little videotape guts? There's a very famous picture of a virus particle that was run over. And its DNA guts looked like videotape coming out of here. That's where this analogy comes from. So you can actually, well, let's look at this analogy. 

DNA is like videotape. It's a linear molecule. If you look at this in the light, what do you see? You open that up, pull that out, and look at it under a light, what does it look like? Do you see pictures? Well, if you do, I'd like to be on what you're on. 
(laughter)

 Whoa! Yeah, this is not film. This is magnetic tape. 

So, all you're seeing here is encoded information. So, if this is linear encoded information, what do you need to decode it? A TV and a VCR. And what do you get out of this when you play it with a TV and a VCR? You get pictures and sounds. And a series of pictures and sounds in a movie happens to be called a scene. And that just happens to rhyme with gene. 
(inaudible)

 Which rhymes with-- I get to be Professor Harold Hill now! 
(laughter)

 Can you make copies of videotape? Can you make edits of videotape? Can you make copies of edits of videotape. So if I gave you two TVs and two VCRs, and a blank tape, and a tape of the Sound of Music, and a tape of the original Terminator, could you make me a version of the Sound of Music that's the regular Sound of Music all the way up to when Julie Andrews leaves the captain to go back to the nunnery, and then the next scene would be Governor Arnold Schwarzenegger saying, "I'll be back," and then the rest of the movie could be the Sound of Music. And if you took that bootleg tape with that extra scene in it, could you make extra copies of it? And when you played those extra copies, would that extra scene pop up? This is one of the powerful things about DNA. One of the powerful things about analogies is that it helps you grasp how things work. But all analogies eventually break down. Because unlike videotape, DNA is alive and evolving. 

If I throw this in a big vat of warm bacterial growth medium, and shake it, and keep it overnight, how many of these do I have in the morning. One kind of wet one. So all analogies eventually break down. But the analogy is very helpful, because DNA is a linear information molecule. It carries information that's encoded, and therefore has to be decoded. And when you decode it, you get genes. And you can copy DNA. You can edit DNA. You can make copies of the edits in DNA. In ten years, this analogy won't be nearly as powerful as it's been over the last 25, because everybody under 15 has never seen one of these. 

But, right now, it's not bad. Next, DNA is-- Is DNA just a concept, or it actually something concrete which you can work with? So let's try extracting some DNA from this stuff. Would you all please get a tube. A tube could look like this with a little pink top, or it might be a blue top, or it might have a red top. It doesn't matter. Would you please get a tube. Pop the top on it for me, please. And pour some of the stuff in there into your hand. Go ahead and tell me what it looks like. 

- Crushed oatmeal. 

- It looks like crushed oatmeal. It also looks like? Fish food. Mmm, there's some good eating. 
(inaudible)

 Yep, when the little piranha rise up to the top of the tank, they're going for your finger, not the wheat germ. So, he suggested it looked like oatmeal. This is also another grain, not oats, but wheat. And right there, through the courtesy of the folks down in Brodhead that do their annual steam thresheree, they gave me a shock of wheat. 

So now a shock of wheat to have. What part of the wheat do we eat? Do we eat the roots? Do we eat the stems? Do we eat the leaves? Do we eat the grain or the seed? This is wheat germ, and that comes from the grain of the wheat germ. And those of you that already have the handout, you can see across the top there are four pictures there. If you take wheat seed and slice it thinly, and look at it under the microscope, you'll see that there's a bunch of little boxes. What's the fancy word in biology for those little boxes? 

Cells. And if you look even closer in the cells, under greater magnification, you'll see there's a little soccer ball thing off to one side, and that's called the...? Nucleus. And in the nucleus, if it's the right time in the cell cycle, you'll be able to see colorful little bodies called chromosomes. Chromosomes are made up of...? DNA and protein. So if you have a tube of wheat germ, you have a tube of a bunch of wheat cells, and a bunch of wheat nuclei, and a bunch of wheat chromosomes, and a bunch of wheat DNA. So are we going to make DNA or are we going to extract DNA? We're going to extract DNA. So here we go. 

Some of you already have the recipe in front of you. Please find the 20 mark on the side of your tube. And then fill that tube up with water to the 20 mark. So the water that you used before, that's in your little bottle, you can go ahead and use, or the one in your cup. Yeah, the 20 mark. And then go ahead and cap it. 
(inaudible)

 Oh, no, not 21! He doesn't listen! And then start shaking. 

It officially says to shake for three minutes. We're going to do a little theory of relativity and go a little faster than that. While we are shaking, would you please have a conversation with the people that you are with over this puzzle question. The original puzzle question is, why bother to study DNA. And one way to answer that is in a parable question. Here's the parable question. Well, why bother to study DNA? Let's look at it this way. If you had a choice between having a plate full of cookies on one hand or the recipe card for cookies on the other hand, which would you take and why? 

- Both! 
(laughter)

- Gosh, Yogi Berra here! Okay, when you come to a fork in the road... So, have a discussion over the relative advantages and disadvantages of taking the plate of cookies versus taking the recipe card. 
(indistinct talking)

- All right! Now, what are the advantages of taking the cookies? 

- Gratification right now. 

- Gratification right now, very good. What are some of the drawbacks? 

- Oh, stomachache? 
(laughter)

- That's a new one. I could live with that. It's hard to have later gratification, if you have it all right now. What's the drawback on having the recipe card? No cookies. 

But what's the advantage? You can make more. What is it about having the recipe card that allows you to make more? What have you got? The ingredients. Do you actually have a pile of sugar and a pile of flour when you have the recipe card? No. So do you have the ingredients when you have the recipe card. No, it's another I-N word that I'm looking for. Not ingredients but information. 

And the root word in there is form. When you have the recipe card, you've got not just the ingredients, which you don't really have, you've got recorded information. That's a very powerful thing. When you can store, retrieve, edit, copy, express, and share information, that's really powerful. That's true whether you're working with a recipe card, with a DVD, or with DNA. So why bother to study DNA? Where's the genetic recipe information recorded? On the DNA. So would you know please stop, pop your top, smell. Stick your digitus in the pukus. 
(light laughter)

 Don't whiff it too hard, you could keel over there. Careful there, okay? What did Goldilocks eat? Porridge, okay. What did Oliver Twist want more of? Gruel. So this is either porridge or gruel. And if you're an Eskimo, this is...? Mush. 

This is breakfast for some people. It's just swollen cells of wheat germ. Next. Would you please take a green tube like this and pop the top on it, and pour the contents in there. Oooh! This is Palmolive dish washing liquid. Oooh! Palmolive, yeah. You could use Dawn. You could use Ivory, even. 

Joy, happiness! Okay, now this stuff takes a long time to drain, so just count to 10,000 slowly, as in one, two, skip a few, 9,9999 and 10,000. Very good. And you can take this home or you can set it here and throw it away. Next, put the lid back on. And this time, instead of shaking real vigorously, please shake like you're a windshield wiper. What's happening here is, cells are like balloons. What's it take to blow up a balloon? Air. And what's it take to pop a balloon? 

A pin. Cells are like balloons, but instead of inflating the cell with air, what did we swell the cell with? Water. And now, instead of popping the cells with pins, what are we popping them with? The detergent. In the detergent is a thing called sodium dodecyl sulfate, sodium lauryl sulfate is another name for it. The key thing is, it's going in there and wrecking the cell membranes, and popping those. It can wreck the nuclear membrane and pop those. We are making these little cells spill their DNA guts, and all their other guts, too. So that's why we're doing this. 

And the people that developed this said not to shake vigorously, because you get a bunch of foam. That's why we're waving like this. This is supposed to go on for three minutes, too, but we are going to apply the theory of relativity. We are relatively done. So please stop. Pop the top. Smell again. Take your digitus stick it in the pukus. There's some good eating! And now, I'm going to show you how to do this, and then you guys can all do this. 

But I need to show you this, because this is a little tricky. I'm going to issue a bad joke alert. Here's the bad joke alert. These bottles are like basketball players. They dribble. 
(light laughter)

 Thank you. I would cover my mouth, too. That was bad. You were warned. 

Now, because they dribble, please do not do them over the carpet. Please do it over the table. We have paper towels. Don't do this straight up and down, vertical, like that. Do it almost flat, like that. And pour slowly, using the adverbial form. Let the blue stuff float up on top. Then, you have two phases. You've got the yellow goo down below, and the blue stuff up above. And if you look right through here like this, you can see some white veil stuff. 

Take your stick and stick the stick up in the blue. Don't go down in the yellow goo. Make a nice, slow tornado. This is your chance to be Auntie Em in Dorothy. Oooh, look at that, it's a twister. And twist some of that glop around your stick and pull it out. That is a DNA glob. You can snap your lid back, if you need to. There's these little racks here that look like this. Set it up so the big rack hole is there, and you can use that to steady your tube. 

Then there's some clean, clear tubes on every rack. And you can take one of those clean, clear tubes and take that white glop in there and leave it in that tube, and take home a souvenir of DNA glop. Is this highly purified DNA? 
(laughter)

 No. It's not highly purified DNA, like that little red-capped tube that we started with. This is DNA glop. There's DNA in here, but there's also polysaccharide and proteins. But does this give you the idea to respond to that original question, is DNA just a concept, or is it something concrete that you can see. And if you get enough of it, you can work with it. 
(indistinct talking)

 It does. Okay. 

- Wait a minute, is that all it takes to extract DNA? 

- Is that all it takes to extract DNA? That's all it takes to extract a DNA glob. If you really want to do this to get highly purified DNA, you won't be able to do this kitchen chemistry. You have to start with a buffer, swell the cells, break the cells open, and then there's different approaches that you can take. One approach that I used long ago as a grad student was to use phenol to extract the nucleic acids out and to denature the proteins, and that type of thing. And then you take the water that's left over from that, and you do add alcohol to make the DNA that's up in the water precipitate. 

Then you can also use columns that specifically attach to DNA, and let the other stuff wash through, and then you loot the stuff off the DNA. There's other ways to do it than this. But this is a way that you can do using kitchen chemistry, and to get across the feeling for the idea that DNA isn't just a concept. DNA is something concrete that you can work with. Okay? Did everybody get some? Yes. Now, we're going to look at some-- If you want to take the next ten or 15 seconds to clean up, and everything, the next thing we're going to do is look at some models of DNA. Then we're going to make a human DNA model. So we'll be back in about ten or 15 seconds. 

Oh, would you like paper towels? That would be a good idea. Now we're going to move on to a model of DNA, which was published in April, 1953. There were three papers published cheek by jowl by cheek by jowl. One was by Watson and Crick, one was by Rosalind Franklin and her associate, and one was by Maurice Wilkins and his associate. In those three papers, there was one that most people remember. And that's the one that's got the famous pen and ink drawing, is the Watson and Crick model. And this is a molecular model, showing atom by atom of what DNA can look like. The key thing that they showed in that short, little one-page paper was DNA was a double helix. There were four big ideas in the Watson/Crick model from what I can get out of it. 

And that is, DNA is double stranded, anti-parallel, the bases are complementary, and it's twisted like a helix. I want to go through all four of those, so we should get an idea of what it's like. So when we look at this model, we can see that it's like a twisted ladder. There are two sides to the twisted ladder, not three. There's one model that projected that DNA might be triple stranded. But for the most part, DNA exists in nature as double strands. So it's like a ladder that's twisted. There are two sides to it. Then the rungs are formed by four different compounds, or four different bases, just kind of like baseball. There's four bases in baseball, first, second, third, and home. 

Somebody is going to correct me and say pitcher's mound is also a base, and I will concede that fact, sorry about that. But let's go with the idea that there are four bases or four letters that make up DNA. How many letters are there in the English alphabet, by the way? Twenty-six. Can you give me an example of an alphabet that has only two letters? Binary code, and what's another one? Morse code, yeah. And in Morse code, the two letters are dots and dash, very good. What hath God wrought? Okay, so in DNA, we don't have 26 letters, we don't have two letters. 

We have four letters, or four bases. And many of you have heard their names. They go by A, T, G, and C. And the next big thing that they figured out with the Watson/Crick model was of those four letters, if A is on one side, T is on the other. And if T is on one side, then A is on the other. And if C is on one side, G is on the other. And if G is on one side, then C is on the other. What that means is, if you take that model and peel it off into two single strands, you have all the information on one strand to figure out what's on the other strand. That's a very big part of this elegant model. This is one way to look at this. 

This one shows that DNA is double stranded, complementary, and twisted or helical. It really doesn't show that it's anti-parallel. And so we're now going to make a human DNA model that will get across three of the four big ideas of the Watson/Crick model. This one gets across three, but it doesn't get across anti-parallel. The one that we're about to make gets across three: DNA is double stranded, complementary and anti-parallel. It will not show the twisted aspect of it. So in order to make a human DNA model, I'm going to need to invite the six of you to come up here. Can you come up here? We're going to make two teams. It's going to be like two teams shaking hands after a baseball game. 

So if you could line up behind me. Would you like to be the coach of the second team? 

- Sure. 

- Okay, we're going to need another person, because I'm going to do this also. Do you want to ask your son to come up? Good. So, this is like two teams shaking hands after a baseball game. How many players are we? Four here and four there. Could we have more people on each team? 

Sure. So instead of doing like you usually do, where you shake hands with everybody and walk by, once I get to the fourth person, I'm going to stop. And once he gets to the fourth person, he's going to stop. So, say nice game. Nice game. Nice game. And nice game. Now, shake hands with the person opposite you on the other team. Are we double stranded? Yes. 

And are we parallel? Which way is my team facing? Which way is that team facing? Oh! Now, would we all take our left hands and put it on the left shoulder of the person in front of us on our team. The other left. Very good. Now we are double stranded, anti-parallel. And say something nice to the person opposite you. Nice game. 

Now we're complementary. Okay? The handshakes are all the same, unfortunately. So we're going to have to do two different handshakes with four different configurations. The first handshake looks like a C. And C is always opposite G. So would my team please make a C handshake. And your left hand just goes off into the air. Sorry about that, I know you wanted to. 

- I didn't. 

- I know, that's all right. Now go ahead and face the wall. You've been bad! Now my team is going to make the C, and you guys are going to make the fist. And they fit together, just like that. Now they're going to make the C, and our team is going to make the fist. Ooh, very good. So that's the G-C handshake. Next, we have to make the A-T handshake. This, in the United States in North America, what does this mean? 

- A-okay. 

- A-okay, and what's one of the letters we have to do? A. Unfortunately, in the rest of the world, this doesn't mean A-okay. 
(laughter)

 It's bad. It's a letter that begins with A and ends in S and S. Okay? So you've got to be careful doing this in other places. We're going to say this A-okay, and it's going to be like a basketball hoop. 

To which you're going to put a little hook in it. So if my team makes the basketball hoop for A, you make a little T. Notice that the A and T is not as strong as the G-C handshake. That's good, because the G-C bond is stronger than the A-T bond. Next, you guys make the A and we'll do the T. Very good. Now, can you guys take a little step to your left, and we'll take a little step to our left. We're going to do a little Army thing and get all dress-right-dress, as best you can. Now, would you be an A. Sir, would you be a T. 

Would you be a G. And would you be a C. We will respond accordingly. Are we double stranded? 

- Mm-hmm. 

- Are we anti-parallel? 

- Mm-hmm. 

- And are we complementary? Yes. Not only that, if we had a little bit more room, we could do the Witch of the West thing and melt. 

So we're going to try to do that. And look, we can melt into two single strands. 
(whistles)

 And if we had eight more people come up here, could you fill-in, and could we end up with two double strands? That gets across how DNA can replicate. Next, can we come back together? Yes, we can. That's called annealing, which is really important, because single stranded DNA can be used to find its complement in a big mixture of other DNAs. So this is a huge idea. Next, DNA has to mutate. 

So what would happen if he changed his hand? We would no longer have a good match. But next time we went through to replicate, instead of-- He used to be an A, now he's a G. So what would have to fill in when he replicated would be a C, instead of a T. What happens if somebody bumped in there and budged in line? Or what happens if somebody steps out of line. You're outta line! Those are all different ways that you can show how DNA can mutate. So the human DNA model is not a model of human DNA. It's just like every other DNA. 

It's a model DNA made out of humans. It's double stranded, anti-parallel and complementary. It's not twisted, although some of us are twisted. We can't show the helical aspects of this, but this is one of the most powerful models of DNA, because it shows so much of the biochemistry. Now, if you guys drop your hands and go back to your seats, I want to show that DNA is made up of subunits. We had eight subunits up here, eight bases. And the human body can be three key aspects. My left hand served as a phosphate group. This part serves as the deoxyribose. And the right hand serves as the nitrogenous space. 

It could either be a C, G, A or T. DNA can be built up or pulled apart, base by base by base. So you can get a stronger idea of what DNA is built like, I think. This is a great way to look at DNA, and so is that other model, but the human DNA model gives you a chance to look at DNA in a way that these models don't allow. One last thing. What does DNA stand for? Truth, justice and-- No, it doesn't. DNA stands for Deoxyribonucleic acid. Where did it get its name? Frederick Miescher discovered it in the early 1870s. 

It's called an acid because when he stained the cells he was looking at, he used a stain that liked to stick to things that were acidic. So he knew it was something that was an acid in the cell. And in what part of the cell did he see it mostly in? The nucleus. And the adjective form of nucleus is nucleic. So it was a nucleic acid. Later on, people figured out that one of the key components in DNA is a five carbon sugar called ribose. Except it's not quite ribose. It's ribose missing an oxygen. So what do you end up calling it? 

Deoxy-ribo-nucleic acid. So, one way to understand where the name came from, is to start at the end and work your way back to the front. So those are some of the activities that we do with DNA, the code of life. There are analogies, activities, and experiments, metaphors. The whole idea is to give you a better idea of how to think about DNA and how to get a grip on DNA. We're going to be finishing up now. Now we're going to go look at the DNA fountain out in the lobby. But the folks from Wisconsin Public Television probably can't follow us on that. So why don't I take any questions now, and then when we're done with questions, we'll go through and look at the DNA fountain in the lobby. Yes? 

- What is the sequence? Is there a stem cell, then a cell, DNA, or is DNA first, then stem cell, then cell. 

- What is the sequence, is there DNA first and then stem cell and then cells. There's a chicken and there's an egg. Hmm. So, in order to have stem cells, oh, so this is a relative size. I think I'm good. Within stem cells is a nucleus, and within the nucleus, if it's a human, how many chromosomes do we have, 46, or 23 pair. So the cool thing about stem cells is they can grow, divide, make copies of all 46 of those chromosomes and go from one cell to two cells. So you start with one and you can go into two. 

So when cells go through that process, they make copies of all 46 chromosomes, so that both daughter cells get a full complement. The big question is, which genes get turned on and which genes get turned off, because what can a stem cell do? It doesn't do much, except for it can grow and divide. And the cells that it spins off can grow into any of the 200-and-some types of tissue cells in the human body. That's a very powerful thing. So I think you asked me a question about scale. DNA is a molecule. If you wrap enough of those up, you can get a chromosome. Chromosomes are in the nucleus. The nucleus is within the cell. 

Does that make sense? Is that addressing your question? Okay, other questions. Tom. 

- How many genes in the human genome? You mentioned 30,000. I've heard the number 20,000. 

- I don't know. I've heard 20,000. I've heard 30,000. 

I've heard 25,000. It's a good question to me, if it's been sequenced, why don't they know how many genes there are. And I think it gets at this issue of the difference between a stretch of DNA and a gene. And there was the concept of the gene before even people realized DNA was the informational molecule. And I think that's, what I look at is how do you explain the difference between the sequence of DNA if the human genome is known, why don't we know rock solid, just exactly how many genes there are. And I think that's the answer, as I understand it. I don't think it's the best answer out there, but that's how I understand it, is that they're not exactly sure how many different functions there are for each of those stretches of DNA. Yes? 
(inaudible)

 How much of our DNA makes stuff, and how much of it doesn't. 

I don't know, but it used to be that people would talk about junk DNA. And I think you've got to be really careful about talking about oh, this is junk DNA. It's one thing to say we don't know what that stuff does, and it's another thing to say that it's junk. Certain model organisms are selected, because they have very economical use of their DNA. For example, arabidopsis, to use the phrase "junk DNA," is this little plant, water cress, that's been a model organism of choice for plant scientists for about the last 25 years. And compared to corn, it has very economical use of its DNA, very little junk DNA. But as I said before, I'm reluctant to use that phrase, just because we haven't figured out what it does yet doesn't mean it doesn't have a function. Other questions? 

- Some types of disease that cause cancer, certain chromosomes, instead of creating themselves, will cross over. What causes that? 

- I'm a plant guy. The question is, what causes crossing over of chromosomes. And I don't know what the trigger is. There are people that understand the mechanism, and whether it's homologous or heterologous, and whether some cells have that occur at a much higher rate than others. And I don't know how. That's a good question for which I don't have a good answer. Other questions? If not, thank you very much. I hope you come next week for the lecture. We'll go out and look at the DNA fountain in the atrium. 

If you want, we can make a much longer human DNA model, if everybody would like to do that. Thanks again for coming tonight. 
(applause)