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JOE PALCA, host:

This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News. I'm Joe Palca. Ira Flatow's away.

Well, it's that time of the year - the time when some of the world's leading scientists hear a little voice in their head saying, I wonder if I'll get the call.

This year, George Smoot and John Mather got the call. They won the 2006 Nobel Prize in physics for their exploration of the cosmic microwave background radiation and discoveries about the infant universe. The data they used came from a satellite named COBE, or Cosmic Background Explorer.

Smoot's work focused on measuring minute variations in this background radiation. He's an astrophysicist at Lawrence Berkeley National Laboratory and a professor of physics at the University of California, Berkeley. He joins me today from his office there. Welcome to the program, Dr. Smoot.

Well, I guess he'll be joining us shortly.

And John Mather coordinated the entire COBE project and helped show that the background behaves just as theoretical models had predicted. He is a senior astrophysicist at NASA's Goddard Space Flight Center in Greenbelt, Maryland, and he joins me from a studio up there in Greenbelt.

Are you there, Dr. Mather?

Dr. JOHN MATHER (2006 Nobel Laureate in Physics): Yes, I'm here. Hello, Joe.

PALCA: Okay. And now I gather we have George Smoot on the line as well. Welcome, Dr. Smoot.

Dr. GEORGE SMOOT (2006 Nobel Laureate in Physics): Yes, thank you.

PALCA: Okay. Now, if you'd like to join us on our exploration of this year's prize-winning research, give us a call. The number is 1-800-989-8255. That's 1-800-989-TALK. And if you want more information about what we'll be talking about this hour, go to our Web site at www.sciencefriday.com, where you'll find links to our topic.

So Dr. Smoot, if I could start with you, I couldn't resist going back to an article I wrote in 1992. I don't know if you recall, but I paid a short visit with you at the South Pole in '91 when you were down there doing some of your Earth-based cosmic background or exploration. And I was writing at the time that you were looking for lumpiness in the universe, and what I wrote was, Smoot's group isn't saying for sure, but they think they've found a critical piece of evidence for cosmic lumpiness.

Was I talking about what we're talking about, that won the prize?

Dr. SMOOT: I'm not sure what you were talking about.

PALCA: Well, that's often the case.

Dr. SMOOT: We were there trying to measure the long wavelengths, the stuff that compliments the instrument that John Mather was the principal investigator for.

PALCA: I see. And - okay, so what we're talking about is the early - not days, but minutes, or fractions of second of the universe. How early are we talking about?

Dr. SMOOT: Well, it depends on what your view is. We have a picture of the universe, which is the universe when it's between three and four hundred thousand years old, but we think we can look from that picture back to much earlier, and it's - we think we're actually able to see things back to a tiny fraction of a second.

PALCA: Hmm.

Dr. SMOOT: But we certainly are confident we can get back to minutes.

PALCA: And - I mean this is the problem, of course, but how far back can you go?

Dr. SMOOT: That's of course, you know, the $64 million question now.

PALCA: Right.

Dr. SMOOT: With inflation. And you know, we're trying to find, you know, using these data and other data, trying to find the relics and the evidence for what happened in the very earliest time, see if we can distinguish what possible beginnings there were for the universe.

PALCA: I got it. Okay, John Mather, maybe I can turn to you. How was the work that you were doing with COBE different from and complimentary with what Dr. Smoot was doing?

Dr. MATHER: Okay, the thing we wanted to measure was the color of this Big Bang radiation to see if it really matched the predictions of the Big Bang theory. So the question that existed a long time ago, when we started off, was: is the Big Bang theory even the right theory for the universe? And the competing theory was called the Steady State theory, that held that although it looks like it's expanding, it didn't really have a beginning; it's always been going on and then replenished as things went.

So our test was to see did the radiation match the Big Bang picture or not? And the answer was, yes, it's effectively perfect, the - almost most perfect agreement we could ever get with this kind of test. It's a few parts per million, 50 parts per million agreement, which is extraordinary.

PALCA: Wow.

Dr. MATHER: So there was no alternative in the end to that explanation. We've only got this one answer that fits the data.

PALCA: And I've read that - I mean KOBE was launched in 1989, after some delay and frustration I know. And I've read that the data that showed this curve that you're describing was available very soon after launch, is that true?

Dr. MATHER: That's right. We knew in a few weeks that the instrument was working. And one morning I came in and my colleagues had signed the interferogram and said this is it, are you ready to go? And so it just took a few more weeks after that to get the data checked out and ready to show our astronomer colleagues. Then it took quite a few more years to get all the way down to 50 parts per million. But right away we knew we had done the job we had set out to do.

PALCA: Sure. Sure. I wonder if I can go back to Dr. Smoot. I mean what do the current set of instruments do to help complete the picture that KOBE presented to you?

Dr. SMOOT: What basically KOBE did was through John's instrument it showed that it - we knew what the radiation was and what its origin was; and then through my team's instrument that there were these fluctuations that we think were going to become the seeds of the galaxies, but were an indication of the universe began and that people exploited them by measuring them. With more sensitivity and much (unintelligible) scale, they would be able to actually see how the universe was responding to its initial conditions and be able to sort out, you know, what the universe was made out of and how it was developing. And that's what - there's been a series of balloon-born and ground-based, especially the WMAP satellite, and eventually the (unintelligible) satellite in a year or two, that are going to continue to exploit this and really get us to understand what the basic parameters are. We think there are about 15 parameters that describe the universe very well in a physically average sense.

PALCA: All right. I'd like to invite our listener's to join us. Our number is 800-989-8255. That's 800-989-TALK. And let's take a call now from Patrick in Louisville, Kentucky. Patrick, welcome to SCIENCE FRIDAY.

PATRICK (Caller): Hi, thanks.

PALCA. Sure.

PATRICK: I have a question. I've always wanted a certain point clarified. You know, I read science as an amateur, science books. And the Big Bang, what exactly is the size of the Big Bang? Sometimes I read where scientists say it happened everywhere all at once. Other times I read where its origin was an infinitesimally small point, but if there was nothing outside of that point, what's there to size it by?

PALCA: That's one of those…

Dr. MATHER: That's a big question.

PALCA: Yeah, John Mather, go ahead.

Dr. MATHER: Yeah. Everyone asks us this question. And the sort of short version is, the whole universe that we can see now was indeed compressed into a tiny volume, but we're inside it, you know, we only can see from inside it. So this tiny volume included us, whatever the things were that made us eventually. So we don't know what's outside this volume, if there is indeed, but we imagine, and theory says it's possible, that it goes on forever.

PALCA: Well, that's pretty big. Let's try another call. And Jeff in Palo Alto, welcome to the program.

JEFF (Caller): Yes, I have an anecdotal, personal question. I attended MIT, and on the bridge going across the Charles River, as a prank the MIT students measured the bridge using somebody named Smoot as the unit of measure. And I've forgotten the exact number of Smoots that that bridge is long, but I'm curious if Dr. Smoot is the Smoot in question.

Dr. SMOOT: Well, I guess I get to answer.

PALCA: Yes, I think so.

Dr. SMOOT: The bridge is 364.4 plus one ear long. And for years I've had to deny it was me, until it became a national landmark, and then my cousin Oliver 'fessed up that it was him. He was the shortest pledge in his fraternity and they - they made the other pledges, you know, use him as a measuring stick to measure the length across the bridge. Because it's so cold when you walk across the bridge, you don't want to put your head up to see how far it is; you want to keep your head down to keep the wind off. And you can look by the Smoot marks.

PALCA: So it's the O. Smoot marks, not the G. Smoot marks.

Dr. SMOOT: Right.

PALCA: I see. Okay, Jeff, I guess now we've cleared up one of the great mysteries of life.

JEFF: Oh, it's been a mystery for years and years, ever since the COBE (unintelligible) I've been curious if it was the same Smoot. But at least it's all in the family.

PALCA: Thanks very much for calling. Let's go now to Christine is Portland, Oregon. Christine, welcome to SCIENCE FRIDAY.

CHRISTINE (Caller): Hi, thanks for taking my call.

PALCA: Sure.

CHRISTINE: I was calling to say congratulations first, and then I also had the question of how frequently do theoretical astrophysicists win the award versus experimentalists?

PALCA: Hmm. Well, these gentlemen are probably just getting to terms with the fact that they've joined this band of people, but maybe one of them has a answer - John Mather perhaps?

Dr. MATHER: Yeah, mostly neither.

(Soundbite of laughter)

Only recently have awards been made in astronomy and astrophysics.

PALCA: George Smoot, do you think that's...

Dr. SMOOT: I would agree that essentially it's been all observists and experimentalists. The only kind of exception you could have said was Albert Einstein, but he got it for non astrophysics work.

CHRISTINE: Oh, I see.

PALCA: OK.

CHRISTINE: But then just a variation between theoretical scientists versus the experimentalists?

Dr. SMOOT: Well, I think that astrophysics, especially cosmology, is such a young science that it will be awhile before the theories are sufficiently proven that they, you know, the Nobel Committee is confident that they can give the prize and have it be correct.

PALCA: All right, thank you for that question. I guess you're going to have to leave in a couple of minutes I understand, Dr. Smoot, and I appreciate your taking the time. But everybody...

Dr. SMOOT: I'm actually having my class now.

(Soundbite of laughter)

PALCA: Oh, really? Oh, well, that's fair enough...

Dr. SMOOT: (unintelligible)

PALCA: What are you teaching?

Dr. SMOOT: Well, I'm teaching a course in - we just finished thermophysics, and now we're doing electromagnetism...

PALCA: Do you find that...

Dr. SMOOT: ...teaching Gauss's Law.

PALCA: Do people pay closer attention now, or you can't tell yet?

Dr. SMOOT: Well, they certainly should have paid attention because there was a lot of press in class last time and it was midterm that night, so.

PALCA: I got it. Well, I just have to ask, because everybody is always curious and you probably answered this a million times, but, you know, what was it like when you got the call? Obviously in California it was pretty early in the morning.

Dr. SMOOT: It was just before three o'clock, and I was very surprised. Because, you know, first, it was the middle of the night, and second of all, I have an unlisted cell phone. But somehow they managed to get a hold of it.

PALCA: Wow, those guys are good.

Dr. SMOOT: They are.

PALCA: And they have friends in high places.

Dr. SMOOT: Right.

PALCA: OK, well, we can let you go, and I guess thank you very much...

Dr. SMOOT: I wanted to say hi to John. We haven't had time to talk yet.

PALCA: That's right. It's - I guess you guys...

Dr. MATHER: Yes, hi, George.

(Soundbite of laughter)

PALCA: You guys...

Dr. SMOOT: (unintelligible) I'd like to call you about who we might want to take with us.

(Soundbite of laughter)

Dr. MATHER: Absolutely.

PALCA: How many guests do you get? Do you know?

Dr. SMOOT: I - they say six, but you can buy 10 more tickets or something.

PALCA: Oh, that's pretty nice. Well, you could put them on eBay and get - probably get a lot of money for them - double the prize money.

Dr. SMOOT: I've got a family and, you know, others.

PALCA: I see. Well, you know, if you're looking for people, I'll be happy to go.

(Soundbite of laughter)

PALCA: Anyway - listen, I've seen you in the southern hemisphere. I should at least see you in the northern hemisphere, don't you think?

Dr. SMOOT: That's right.

PALCA: Anyway, thanks very much for joining us. Dr. Mather, I gather you can stay for a few more minutes, so we'll be happy to have you hang around.

Dr. MATHER: Yeah, another few moments are fine, yes.

PALCA: And I hope everybody else stays with us after we take this short break. This is TALK OF THE NATION from NPR News.

(Soundbite of music)

From NPR News, this is TALK OF THE NATION: SCIENCE FRIDAY, and I am Joe Palca.

We're talking this hour about this year's Nobel Prizes, and right now we're talking with John Mather, winner - with George Smoot - of the 2006 Nobel Prize in Physics. He's also a senior astrophysicist at NASA's Goddard Space Flight Center in Greenbelt, Maryland. And I guess we said Dr. Smoot had to go to class.

But Dr. Mather, I wanted to ask you - you're now working on the new - the replacement for the Hubble Space Telescope. How is that going to take this story forward?

Dr. MATHER: Good question. We are planning to build this so that we can see the very first stars and galaxies that lit up after the Big Bang, so that's one of our key topics. And the telescope will also be amazingly powerful for measurements of galaxies turning stars on, for stars forming, for planets forming around stars, even for discovering how we might possibly have come to exist here on Earth - how a planet like Earth could come to support life.

PALCA: There's just been a whole wealth of new planets that, I guess, the current space telescope has discovered. What do you think that's going to tell us about? I mean I guess it pushes us back a little bit further from the center of the universe that we on Earth used to think we were.

Dr. MATHER: Yeah, I think our center of the universe is still us for us.

(Soundbite of laughter)

PALCA: Right.

Dr. MATHER: But we can hardly think that we're alone anymore. There are certainly planets out there in great numbers, and presumably there are some like our own planet, but we don't know where they are yet.

PALCA: OK, let's take one more call now and go to Katherine(ph) in Moraga, California. Welcome to SCIENCE FRIDAY, Katherine.

KATHERINE (Caller): Oh, thank you so much for taking my call.

PALCA: You're welcome.

KATHERINE: I suspect that I'm like probably the majority of the listeners, where we're just fascinated by this. It's intriguing. It's really just - but, you know, most of us don't even, you know, know how to add a checkbook for numbers, much less know physics and all that. And we see the pictures from the Hubble Space, you know, satellite, and it's like…

Could you quantify for us, or verbalize for us, what the beginning - how do you quantify that for someone that knows nothing about what you do as a profession, but we see so many and hear so much about it? How would - what does the beginning look like, or how would you tell new students about - to quantify that in their heads, like wrap around it?

PALCA: Wow, great question, Katherine.

Dr. MATHER: Oh, you know, it's so extreme that it's impossible to have a big enough, extreme enough word. The entire universe of everything we can see for billions of light years around us compressed into the size of a billiard ball? Well, that's extreme, but I can't make it sound anymore extreme. It's the most. It's the ultimate. So it's the biggest bang that we could imagine, and so...

KATHERINE: So does it start from like black nothing and then became - I mean...

(Soundbite of laughter)

Dr. MATHER: We don't know. This is the biggest mystery, too. There's just no way to tell what's out there on the other side of it if there was another side of it or even to know if this is the only universe.

KATHERINE: OK.

Dr. MATHER: There could be many of them.

PALCA: Katherine, you know, you're asking the most appropriate and most difficult questions probably that anyone could answer. But I really appreciate that you took the time to call because that's sort of - it's one of the things about these prizes, that they provide such an interesting time to let people get interested in science. And so, you know, what do you - I was going to ask, John Mather, how are you planning to use this? Because I know a lot of Nobel winners have gone on to get very interested in public understanding of science after they won their prizes.

Dr. MATHER: Well, good question, and it's way too soon for me to know the answer to that.

(Soundbite of laughter)

PALCA: Good.

Dr. MATHER: Right now I'm just talking to everybody that wants to talk.

PALCA: Mm-hmm.

Dr. MATHER: And I'm being invited to go everywhere and speak to everyone, and so we'll see what develops.

PALCA: Well...

Dr. MATHER: Clearly, the public is fascinated with what we do, and we'd like to help them understand.

PALCA: That's great. And I guess, since I asked Dr. Smoot, I should ask you as well. How did you hear from the committee, the Nobel Committee?

Dr. MATHER: Well, I got a phone call at a quarter of six in the morning in Eastern time here, and I was amazed. There's just no possibility of really knowing if such a thing would ever happen. People have been telling us for years that it should happen, but you know, you look at the lists of what people have done before in other fields of physics, and it's just astonishing what people have done. So I never dreamed that I would really be one of those people.

PALCA: Well, I guess maybe what we should do is ask you in six months whether you feel more like one of those people because I think it grows on you, but we'll see. Anyway, thanks very much for joining us today. I appreciate it very much.

Dr. MATHER: Thank you. It's a pleasure.

PALCA: OK, John Mather is a winner of the 2006 Nobel Prize in Physics and a senior astrophysicist at NASA's Goddard Space Flight Center in Greenbelt, Maryland.

And now we're on to chemistry. This year's Nobel Prize in Chemistry will be award to Roger Kornberg of Stanford University. Dr. Kornberg studies transcription. That's when cells take the information stored in genes and use that information as a blueprint for making proteins. Dr. Kornberg and his colleagues were the first to create an actual picture of that process with a resolution so sharp that separate atoms are visible.

Now we're sort of in a funny position here, because Dr. Kornberg was in Pittsburgh yesterday, and he flew back to California early this morning. And he's, as we understand it, heading for his office. And so, it's even possible that in the middle of the next few minutes he'll show up in his office and we'll have a chance to talk to him. But in the meantime, his colleague, David Bushnell has agreed to talk with us about Dr. Kornberg's work. And Dr. Bushnell is a research associate in Roger Kornberg's laboratory at Stanford University's School of Medicine, in Stanford, California. So, David Bushnell, thanks for joining us.

Dr. DAVID BUSHNELL (Stanford University): Oh, it's really my pleasure. I'm thrilled to be talking to you on this occasion.

PALCA: I can imag - it's kind of - I guess, you know - having toiled in a lab myself, at one point, it's hard to know that life exists outside the lab, sometime. And when it's brought to you this graphically, I'm sure it's quite a wakeup call.

Dr. BUSHNELL: Well, it was very amusing to see the media circus here on Wednesday. Usually we're toiling away in obscurity. And those of us, sort of on the fringes of Roger, were getting interviewed and photographed - and even some of us ended up on the - at least the local news.

PALCA: Well, now you've made national news, this is great.

Dr. BUSHNELL: I'm very happy.

PALCA: OK. Well, maybe we could get you to go back and - I mean this is another topic - very - this is not one of those things in chemistry that people can finish the sentence by saying: and this is could lead to a cure for this or a cure for that. It's one of these very, very basic parts of biology that is critical for understanding how genes work, but a little bit hard, maybe, for people to visualize. Have you come up with good metaphors to explain what this work is about?

Dr. BUSHNELL: Oh, God no.

PALCA: Oh, we called the wrong person.

Dr. BUSHNELL: In fact, the - probably the best metaphor is one I would steal from Nova, where they were, in fact, talking about RNAi. Where you can think of biology - the three major macromolecules in biology. The DNA on one side, which is the information storage. Protein on the other, which is the machinery that does all the work. And they can't talk to each other directly, because the DNA is sequestered in the cell. And so the analogy they used on this Nova program, was, you can think of the DNA as the cookbook and the protein are cooks. But the cookbooks are stored away, locked in a tower that no one can really get to. And in order to communicate, you need to have some scribes transcribing these recipes and throwing them out the window. And so, what we work on is that step of writing the recipes and how - which recipe gets chosen and, in fact how it gets written out.

PALCA: I just - I saw the Nova program you're referring to and I can't resist complimenting my colleague, Robert Krulwich, because he was actually the presenter on that program - and I thought that was a brilliant description and I'm glad to hear that you thought it was…

Dr. BUSHNELL: The best one I've seen and refer people to it all the time, because it is a very brilliant analogy and one many people can grasp easily.

PALCA: Yeah, because there's this great thing of the scribe throwing the recipes out the window where they're caught by the cooks down below.

Dr. BUSHNELL: Exactly.

PALCA: But, why is this considered chemistry? This is a Nobel Prize in chemistry we're talking about, and not biology.

Dr. BUSHNELL: Well, at its core is a chemical reaction. It's the formation of a Phosphodiester bond, the addition of a nucleotide to a strand. So there's a lot of very complicated chemistry going on. And all of the rules that govern what gets transcribed, they're all governed by chemistry. It's electrostatics, it's hydrogen bonds, it's Vanderwall forces. This is really all understandable through chemistry. It's still very complex, so we can't completely model it at this point, but hopefully we'll be able to.

PALCA: I suppose this is where the chemical world, as defined by bonds and interactions between atoms starts to shift into the living world, and I guess that's a shift that a lot of people are very interested in.

Dr. BUSHNELL: Absolutely, and it's a very, very critical shift. I mean we need to understand in chemical detail how this works. And hopefully if we can get a complete enough picture and a complete enough understanding on how it works, we will be able to control it.

PALCA: All right. Well, we're talking about the scientific research that was awarded this year's Nobel Prize in Chemistry, and we'd like to hear from you. Our number is 800-989-8255. And let's take a call now from William in Davenport, Iowa. William welcome to the program.

WILLIAM (Caller): Yes, thank you, Dr. Kornberg. I'm a physical chemist, and can you give me a reference to popular literature that shows these depictions of your discreet atoms? Otherwise, what is the reference to the basic work?

PALCA: Well, William, actually were talking with David Bushnell. And there is a chance still that Roger Kornberg might join us. But maybe you can answer that question, David Bushnell.

WILLIAM: Oh, okay.

Dr. BUSHNELL: The depository for the actual coordinates for the atoms is this protein databank which is maintained by Rutgers, and it's publicly available to anyone. You can actually download the coordinates and view them on your own computer with any number of programs and play with these molecules yourself. There is - if you just to the PDB and search for the...

PALCA: I'm sorry, PDB?

Dr. BUSHNELL: Protein Data Bank - I think it's PDB.org I'm not - I always use Google or something to find it. And search for Roger, you'll come with a whole slew of structures with their atomic coordinates that you can then examine at your leisure.

PALCA: And our there any lay representations of this? There was one in the Nobel Prize Web site that gave a kind of an interesting picture of what was going on, but maybe you know of others that did a good job.

Dr. BUSHNELL: Well, there was one several years ago that was put out by Stanford Press when we had - the science papers were published. I believe that is still available on Stanford's Web site. I'm not 100 percent certain - I am not aware of any sort of popular science.

PALCA: Yes.

Dr. BUSHNELL: I think the closest would be the FEBS letters.

PALCA: I'm sorry, the FEBS letters?

Dr. BUSHNELL: There is a FEBS letter...

PALCA: What does that stand for.

Dr. BUSHNELL: FEBS is - Oh, my God.

PALCA: Oh Federation of Experimental Biology, something like that.

Dr. BUSHNELL: Exactly, which was published last year which is sort of Roger -it's based on a lecture Roger gave which is essentially giving a history. But I think it's accessible to scientist; it's not as accessible to lay people.

PALCA: Right. Okay, we'll give people a chance. We're talking with David Bushnell, who's been a colleague of Roger Kornberg - this year's winner of the Nobel Prize for Chemistry.

I'm Joe Palca, and this is TALK OF THE NATION from NPR News.

And, David Bushnell, you've - I want to ask this question because - maybe it's unfair, but what the heck I'm here. You work with Dr. Kornberg; do you ever think, God, I did a lot of that work, why aren't they given me the Nobel Prize?

Dr. BUSHNELL: Well, yeah, sure. It would be nice to receive it. But honestly I have been privileged enough to work with Roger for over a decade now doing the structural work, in fact. But, you know, this work, you know, there were people working on it before I showed up it - really the driving force behind it and the person who kept it going was Roger.

PALCA: Mm-hmm, right.

Dr. BUSHNELL: And you know he's the sort of the CEO; he's the one who puts the team together, he has the big ideas. He helps understand what's going on and he keeps us all motivated and he keeps us all going. And, you know, he gets the lion's share of the credit and, if we fail, the lion's share of the blame.

PALCA: Okay, well fair enough. Let's take one more call now. Mika(ph) in Milwaukee, Wisconsin, welcome to the program.

MIKA (Caller): Hi. Yeah, I was wondering if this was at all related to some of the studies going on about protein folding and whether or not that's kind of going to look into the futures maybe evolutionary medicine; or if you guys have kind of found that through doing a lot of this you guys fell into a more intelligent design because of the way this thing is structured and the way that proteins fold and have to be so meticulous for those things that's it's, you know, possible - impossible that it's chance.

PALCA: Interesting.

MIKA: I wanted to hear his thoughts on that.

PALCA: Okay, Dr. Bushnell, is this impossibly, irreducibly complex or can you figure this out somebody, do you think?

Dr. BUSHNELL: I think we can figure it someday. There are evolutionary hints that tie it to other structures along the way. And it's interesting if you look at the eukaryotic enzyme you can see the prokaryotic enzyme in it.

PALCA: Let's just stop for a second. Eukaryote and prokaryote?

Dr. BUSHNELL: Sorry. We work on baker's yeast, which is a more complicated eukaryotic cell. Bacteria, these E. coli like you're hearing with the spinach and all this recently, they are called prokaryotes. They are generally considered a little less complicated; there is less regulation. The prokaryotic version of (unintelligible) is four sub units. The Eukaryotic version - there's actually three of them, but the one we study is twelve sub units.

PALCA: So, happily, we think of ourselves as more complicated than a bacteria, and at least when it comes to transcribing DNA we are.

Dr. BUSHNELL: We are, but it mostly comes down to the regulation of transcription as opposed to the - if you look right at the active site, right where the specific chemistry is happening where the RNA is being made, they are virtually identical.

But as you get farther and farther away, variations occur. But you can start to look at evolutionary relationship, and there is even some evidence now that there is potentially, very far back in a more simple organisms, very similar things, very similar - my God, my mind's (unintelligible).

PALCA: It's too many interviews in too short of time.

Dr. BUSHNELL: Well, I haven't been giving that many interviews (unintelligible). Like for instance smallpox, which is considered - or vaccinia, which is considered a simpler organism, at least at it's core it's polymerase is remarkably similar to baker's yeast. And so I do think there are steps that could have followed, and it's one of the these where we know from mutation studies you can cause a lot of damage and it'll still work to some extent.

PALCA: Well, Dr. BUSHNELL, I'm hearing the music and that means we're out of time. So I'll thank you very much. Dr. David Bushnell is a research associate in Roger Kornberg's laboratory at the Stanford University School of Medicine. And of course Roger Kornberg just won the Nobel Prize. Thanks for talking with us today, and we'll be back.

From NPR News, this TALK OF THE NATION: SCIENCE FRIDAY. I'm Joe Palca.

A brief program note: Monday on TALK OF THE NATION, as North Korea ups the nuclear ante, we'll look at the dangers of a post proliferation world. And coming up next Thursday, Neal Conan will be here with a special two-hour broadcast exploring the future of deaf education and deaf culture. The deaf community will be able to follow along with live real-time captioning and are encouraged to join the discussion. To find out more, go to npr.org/deafculture. Deaf culture is all one word.

On this program today we're talking about the Nobel Prizes. We've done psychics. We've done chemistry. And now we talk about medicine, or as it's more properly known, physiology or medicine. This year's Nobel will go to Andrew Fire and Craig Mello for a discovering a way of turning off individual genes called RNA interference or gene silencing. Actually, I guess it was nature that kind of discovered it, but they discovered how nature did it.

Remember in last segment we were talking about that process by which cells read the information stored in those DNA to make proteins. Well, it's messenger RNA that makes the information from the genes to the manufacturing center of the cell. Doctors Fire and Mello discovered a mechanism that can halt this process, turning off individual genes and preventing protein production.

Using this technique, scientists can study what specific genes do and develop new treatments for diseases. That's what will be talking about for the rest of this hour. So if you'd like to join us, give us a call. Our number is 1-800-989-8255. That's 1-800-989-TALK. And if you want more information about what we're talking this hour, go to our Web site: www.sciencefriday.com, where you'll find links to our topic.

And now I'm very pleased actually both personally and professionally to welcome Andrew Fire to the program. Andrew Fire is the winner, with Craig Mello, of this year's Nobel Prize in Physiology or Medicine, and he's a professor pathology and of genetics at Stanford University School of Medicine at Stanford, California. And he joins me from his office there. Congratulations, Dr. Fire.

Dr. ANDREW FIRE (Nobel Prize Recipient; Professor of Pathology and Genetics, Stanford University): Thank you very much.

PALCA: And it's getting so you can't swing a cat on the Stanford campus without hitting a Nobel Prize winner.

Dr. FIRE: I'll watch out for the cats here.

PALCA: Anyway, I guess I wanted to say that the personal reason is maybe it's one of the rewards of working as a science writer for as long as I have that you get to meet these really interesting people along the way. And Andy Fire and I have had a couple of really fascinating conversations in the last couple of years. And it's a really a delight to hear that you've won this prize, and I guess, you know - I'm sure it will change nothing and change everything. Or maybe I'm wrong; maybe you can tell me.

Dr. FIRE: I don't know. It's an interesting adventure.

PALCA: Yeah. Well, let's start I guess as is always necessary to sort of sketch the landscape before the insight. What were you looking for or at that brought you to this observation of RNA interference?

Dr. FIRE: Well, I could start by sketching the landscape. Even before I was looking at anything, people had been trying to do a very simple experiment in plants, and to some extent in fungi; which is say, if we want more of a given protein, we ought to put more of the gene in and see what happens. So they did that. And what they found was that occasionally the experiment worked, but usually not only did it not work but you put more of the gene in and you got less of the protein. And in fact some of the experiments were done in petunias where people - Rich Jorgensen was one the people that did this and Jan Mole(ph) was another - they would put a gene into a petunia to make it more pink and it would get white.

And so what was happening was that the cell was responding to that extra information not by expressing it, not by turning it way up, but by treating it as a challenge, treating it as a statement that something was too active, something was making too much of a good thing, or at least that was the original model. And the cell then knew that there was a problem there. And instead of dumbly just making more of it, it actually shut it down.

PALCA: And this shutting down - well, okay. So what was the observation that made you realize that it was a shutting down mechanism or where was the shutting down taking place?

Dr. FIRE: Well, other people then took up this work - and again this is before we actually were doing very much on it - other people took it up in the plant field and they showed that the gene was still transcribed that was targeted by this mechanism, that was still making RNA; but that very shortly after the RNA was made it was degraded. And so there was some way of the cell sensing that a certain kind of RNA was not doing the think job it should in the cell, and when it sensed that it would go ahead and degrade it.

PALCA: Okay. And so you're not working in petunia's, you're working in the C elegans, which is a little worm. So how did you go about investigating this process in C elgans?

Dr. FIRE: Well, one of the challenges in the plant system was that they were putting in extra DNA and seeing this process and had pretty much worked out that there was some kind of RNA that was produced that was mediating the silencing, mediating the shut off. But it was really hard to figure out what the RNA was. And so there's another key experiment, also not one that we did. It was one done by Sue Guo, who was a graduate student at the time in Cornell. And what Sue did is that she injected not a DNA molecule to make extra bits of a gene but actually an RNA molecule that should have give you extra translation, extra production of a protein. And she saw the same effect. So she could actually mimic this effect without the DNA kind of complexity of it, by just injecting an RNA.

And what that meant is it really, definitively confirmed that this was an RNA-triggered process, as we call it. And it almost meant, experimentally, that we in the worm - doing our experiments in the worm - could put in any kind of RNA that we wanted and do a very quick assay to see if we were shutting off gene expression. And that really allowed it, although it took a couple of years to get all the details settled of what to look for. That allowed us to ask a very straightforward question - Craig Mello's group and our group - to ask the question of what structure in the injected RNA was really important for the gene silencing.

PALCA: And I guess the idea is that once, I mean C. elegans is a nice organism to work with because a lot of genes that are in there have been worked out. So once you know the gene, you can make the piece of RNA - interfering RNA - that will stop that gene from doing its job. Is that right?

Dr. FIRE: Yeah, it's a great thing. It might take an afternoon to make the RNA, or actually probably now there are techniques where it might take an hour or two to make the RNA. And then you inject a worm, and within a couple of days, you're looking at worm that that particular gene is knocked down in.

PALCA: And you talked about two groups, and I know you and Craig Mello have been jointly awarded this, but how was that collaboration-competition working? You were at Carnegie Institute of Washington, and he was at MIT. Is that right?

No, he was at the University of Massachusetts, Amherst.

Dr. FIRE: Actually, University of Massachusetts, Worchester.

PALCA: Worchester, sorry. Thanks, Bill, I never would've been forgiven by them if I had gotten that wrong.

Dr. FIRE: So Craig and I had talked for years, about how DNA, or later RNA, that was put into worms had these sort of amazing effects and unusual, unexpected - sometimes positive, sometimes negative - things. So we really had had a collaboration that was just based on really talking about the science behind it. And we had, in fact, previously collaborated on a number of papers, and of course the two labs also did their own work. And so we would go back and forth between collaborations and independent projects in the two groups, which has continued over the years. So it was a really exciting point at which they had gotten to a stage with the work and then we came in with a little bit different expertise, and I think the combination of those two was what led to just a piece of the puzzle being put in, which was the double-stranded character of the trigger.

And we kind of put that out as a paper. And then, we knew a little bit would happen from that, but there was a really remarkable explosion within a few years of different people with all sorts of other expertise coming into the field and making it happen as a technique and also as a scientific investigation area, much more broadly than in the little roundworm.

PALCA: I have to say, at this point, it really intrigues me. This is one of the drawbacks of being a science journalist. So the paper - one of the papers, important papers - came out in February, 1998 I think.

Dr. FIRE: Right.

PALCA: It was a nature paper. And the Nobel Prize Committee cites that as one of the most important, you know, one of the breakthrough piece of work. And I went back - I asked the library today to see who had covered that, because I was pretty sure I didn't. And do you know what kind of media coverage that paper got?

Dr. FIRE: That paper got no media coverage. It was about nematodes, and it was at a time when nematodes were exciting to a lot of people doing basic research. We get our - the work has been supported by the NIH, and so you can ask - you can say the media coverage hasn't been dramatic. But the public support in the form of NIH funding for basic research on - in this field and in a lot of other fields has been very good over the years, and that's really what's made the work possible.

Somebody realized at some point that if you supported biologists investigating questions in the way that they thought was useful - which often is not to do an experiment in a live person, of course, but to do it in a plant or in a nematode or in a fungus - that you could get answers out that would eventually lead to significant improvements for us.

PALCA: Okay. Let's take a call now and go to Paul in Washington, D.C. Paul, welcome to Science Friday. Paul?

PAUL (Caller): Hi.

PALCA: Hi.

PAUL: My question was whether there's any link or theorized link between RNA mechanism and the regulatory DNA, about, you know, gene expression and gene thoughts(ph) (Unintelligible).

PALCA: Okay, Paul, if I got that right, it's how this switching off of genes is similar to or different than the sort of other genes that actually seem to be in the genome for regulating protein - regulating gene expression.

Dr. FIRE: So in fact, this whole issue of how genes are regulated is a very rich field, and there is regulation at the level of cells decide - don't transcribe it in the first place. They modify the chromosome in an area to simply shut it down or make inaccessible. That's probably the most abundant form of regulation, actually.

And another form of regulation that the RNA interference is a small part of is cases where RNA's transcripts are now made, and you want to shut them down by degrading them. Now that having been said, there's a fascinating process that's been very well-documents in plants and sort of suggested in other systems, whereby if there's RNA interference going on, there is some ability of that process to then feed back and tell the chromosome not to make quite so much of what it's making. So the chromosome actually is smart enough to realize that it's making bad stuff and shut it down. And that - I think the mechanism of that is going to be very exciting. Again, it's best characterized in plant systems.

PALCA: We're talking with Andrew Fire. He's this year's winner of the Nobel Prize in Physiology or Medicine. And we're taking your calls at 1-800-989-8255. I'm Joe Palca and this is TALK OF THE NATION from NPR News.

And let's take another call now and go to Trisha(ph) in San Mateo, California. Trisha, welcome to the program. You're just down the road from Dr. Fire.

TRISHA (Caller): Yes, thank you. My question is if Dr. Fire could comment on any information about curing macular degeneration or - currently, I mean, right now, if there's anything - any research going on with real subjects.

Dr. FIRE: So the question is about a disease called macular degeneration, and there is research going on with that. It's not gotten to the stage where it's an approved treatment for general use, but there are clinical trials going on with the idea of using RNA as a tool - RNAi in particular - as a tool to block the angiogenesis, to block the blood-vessel formation that's part of the process.

PALCA: Right. Maybe we should just explain to people what macular degeneration is. It's a breakdown of the ability of the back of the eyeball to make sense of the visual signals that are coming in, and it's related to this explosion of blood vessels that build up in the back of the eyes. I think that's a reasonably close description.

Dr. FIRE: That sounds good. And I should say I'm not an expert on it. What Joe said is actually more than what I know.

PALCA: But why would switching off a gene in theory be a useful thing for treating a disease like that.

Dr. FIRE: Well, if you can block the vacuolization, the blood-vessel explosion, as you described it, then it turns out you can actually block the progress of the disease. There's probably some underlying problems in the eye, but really the main thing is to keep those blood vessels from forming, and you can actually keep people's vision going.

And so there are a couple of different approaches, not just the RNAi approach, but a couple of different approaches to blocking angiogenesis. And the hope is that those things can provide, at some point, a treatment. And my impression from the early clinical data from the two groups that are doing it is they can safely put double-stranded RNA into the eye and that the early clinical data was encouraging. That doesn't mean that - unfortunately, it doesn't guarantee that it's going to be an available treatment. It has to be done in a much broader context to really know the safety and efficacy of it. But it is the kind of thing where one could look for the areas where clinical trials are being done and trying to enroll in them.

There's a lot of applications of RNA interference that have been proposed clinically, and those things are much earlier stage, where one can't enroll in a trial study. But I should say also that there are other approaches to blocking angiogenesis using monoclonal antibodies, and those are also at fairly advanced stages of trial, to my knowledge. They're not necessarily available.

PALCA: Okay, you know, we're almost out of time, but I read a news story that quoted you as saying that the prize wouldn't change your life of teaching and doing research, but it does mean that you can open a public debate on something and people will listen. What issue were you thinking about bringing to people's attention?

Dr. FIRE: Well, it's, you know, it's been kind of an interesting week. I'm not sure that immediately bringing up an issue is the best thing because it's sort of a week where the science itself should speak, and I think the science here is speaking for the importance of basic research in where we can go in terms of making - eventually understanding how we work and making medical advances. That's not me, necessarily, bringing that forward. That's the whole scientific community that's been involved in this field over the years. I think, though, that there also in an opportunity for somebody in the position of being a prominent scientist, which I guess Craig and I and Roger and the physicists who were awarded are now in that position of being on the lookout for areas, either in society where we're not taking advantage of science, or maybe areas where science could advise the course of the country.

The decisions that we make are not - that the country makes are not decisions of science all the time, they're decisions of policy - what people need. But science can certainly inform that, and that's a goal and role that prominent scientists have is to really facilitate the right expert being available to the people making decisions.

PALCA: Excellent. Okay. I need the 10-second version of how you got the phone call.

Dr. FIRE: I was asleep.

(Soundbite of laughter)

PALCA: Well, it was early.

Dr. FIRE: It was early, yes.

PALCA: Well, that's all the time we have on this program. Thanks very much, Andy Fire.

Dr. FIRE: Thanks very much.

PALCA: Andrew Fire is this year's Nobel Prize winner in physiology or medicine, professor pathology and of genetics at Stanford University School of Medicine in Stanford, California.

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