Cracking the Code of Life

Cracking the Code of Life

PBS Airdate: April 17, 2001

ROBERT KRULWICH: When I look at this—and these are the three billion chemical letters, instructions for a human being—my eyes glaze over. But when scientist Eric Lander looks at this he sees stories.

ERIC LANDER (Whitehead Institute/MIT): The genome is a storybook that's been edited for a couple billion years. And you could take it to bed like A Thousand and One Arabian Nights, and read a different story in the genome every night.

ROBERT KRULWICH: This is the story of one of the greatest scientific adventures ever, and at the heart of it is a small, very powerful molecule, DNA.

For the past ten years, scientists all over the world have been painstakingly trying to read the tiny instructions buried inside our DNA. And now, finally, the "Human Genome" has been decoded.

J. CRAIG VENTER (President, Celera Genomics): We're at the moment that scientists wait for. This is what we wanted to do, you know? We're now examining and interpreting the genetic code.

FRANCIS COLLINS (National Human Genome Research Institute): This is the ultimate imaginable thing that one could do scientifically...is to go and look at our own instruction book and then try to figure out what it's telling us.

ROBERT KRULWICH: And what it's telling us is so surprising and so strange and so unexpected. Fifty percent of the genes in a banana are in us?

ERIC LANDER: How different are you from a banana?

ROBERT KRULWICH: I feel...and I feel I can say this with some authority...very different from a banana.

ERIC LANDER: You may feel different...

ROBERT KRULWICH: I eat a banana.

ERIC LANDER: All the machinery for replicating your DNA, all the machinery for controlling the cell cycle, the cell surface, for making nutrients, all that's the same."

ROBERT KRULWICH: So what does any of this information have to do with you or me? Perhaps more than we could possibly imagine. Which one of us will get cancer or arthritis or Alzheimer's? Will there be cures? Will parents in the future be able to determine their children's genetic destinies?

ERIC LANDER: We've opened a box here that has got a huge amount of valuable information. It is the key to understanding disease and in the long run to curing disease. But having opened it, we're also going to be very uncomfortable with that information for some time to come.

ROBERT KRULWICH: Yes, some of the information you are about to see will make you very uncomfortable. On the other hand, some of it I think you'll find amazing and hopeful.

I'm Robert Krulwich. And tonight we will not only report the latest discoveries of the Human Genome project, you will meet the people who made those discoveries possible, and who competed furiously to be first to be done.

And as you watch our program on the human genome, we will be raising a number of issues: genes and privacy, genes and corporate profits, genes and the odd similarity between you and the yeast. And we'd like to have your thoughts on all these subjects. So please, if you will, log on to NOVA's Website—it's located at pbs.org...it'll be there after the broadcast, so do it after the broadcast—where you can take a survey. The results will be immediately available and continually updated. We'll be right back.

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ROBERT KRULWICH: To begin, let's go back four and some billion years ago to wherever it was that the first speck of life appeared on earth, maybe on the warm surface of a bubble. That speck did something that has gone on uninterrupted ever since. It wrote a message. It was a chemical message that it passed to its children, which then passed it on to its children, and to its children, and so on. The message has passed from the very first organism, all the way down through time, to you and me—like a continuous thread through all living things.

It's more elaborate now, of course, but that message, very simply, is the secret of life. And here is that message contained in this stunning little constellation of chemicals we call DNA. You've seen it in this form, the classic double helix, but since we're going to be spending a lot of time talking about DNA, I wondered, "What does it look like when it's raw, you know, in real life?" So I asked an expert.

ERIC LANDER: DNA has a reputation for being such a mystical high-falutin' sort of molecule—all this information, your future, your heredity. It's actually goop. So this here's DNA.

ROBERT KRULWICH: Professor Eric Lander is a geneticist at MIT's Whitehead Institute.

ERIC LANDER: It's very, very long strands of molecules, these double helices of DNA, which, when you get them all together, just look like little threads of cotton.

ROBERT KRULWICH: And these strands were literally pulled from cells, blood cells or maybe skin cells of a human being?

ERIC LANDER: Whoever contributed this DNA, you can tell from this whether or not they might be at early risk for Alzheimer's disease, you can tell whether or not they might be at early risk for breast cancer. And there's probably about 2000 other things you can tell that we don't know how to tell yet but will be able to tell. And it's really incredibly unlikely that you can tell all that from this. But that's DNA for you. That apparently is the secret of life just hanging off there on the tube.

ROBERT KRULWICH: And already DNA has told us things that no one...no one had expected. It turns out that human beings have only twice as many genes as a fruit fly. Now how can that be? We are such complex and magnificent creatures and fruit flies...well they're fruit flies. DNA also tells us that we are more closely related to worms and to yeast than most of us would ever have imagined.

But how do you read what's inside a molecule? Well, if it's DNA, if you turn it so you can look at it from just the right angle, you will see in the middle what look like steps in a ladder. Each step is made up of two chemicals, cytosine and guanine or thymine and adenine. They come always in pairs, called base pairs, either C and G, or T and A for short. This is, step by step, a code, three billion steps long—the formula for a human being.

ROBERT KRULWICH: We're all familiar with this thing, this shape is very familiar.

ERIC LANDER: ...double helix...

ROBERT KRULWICH: ...double helix. First of all, I'm wondering...this is my version of a DNA molecule. Is this, by the way, what it looks like?

ERIC LANDER: Well, give or take. I mean, a cartoon version, yeah.

ROBERT KRULWICH: Cartoon version?

ERIC LANDER: A little like that or so, yeah.

ROBERT KRULWICH: So there are...in every...almost every cell in your body, if you look deep enough, you will find this chain here?

ERIC LANDER: Oh yes, stuck in the nucleus of your cell.

ROBERT KRULWICH: Now how small is this, if in a real DNA molecule the distance between the two walls is how wide?

ERIC LANDER: Oh golly...

ROBERT KRULWICH: Look at this. He's asking for help.

ERIC LANDER: This distance is about from...this distance is about 10 angstroms.

ROBERT KRULWICH: That's one billionth of a meter when it's clumped up in a very particular way.

ERIC LANDER: Well no, it's curled up some like that but you see it's more than that. You can't curl it up too much because these little negatively charged things will repel each other so you fold it on its...I'm going to break your molecule.

ROBERT KRULWICH: No, don't break my molecule...very valuable.

ERIC LANDER: You got this. And then it's folded up like this. And then those are folded up on top of each other. And so, in fact, if you were to stretch out all of the DNA it would run, oh, I don't know, thousands and thousands of feet.

ROBERT KRULWICH: But the main thing about this is the ladder, the steps of this ladder. If I knew it was A and T and C and C and G and G and A...

ERIC LANDER: No, no. It's not G and G, it's G and C.

ROBERT KRULWICH: I'm sorry, whatever the rules are of the grammar, yeah...if I could read each of the individual ladders, I might find the picture of what?

ERIC LANDER: Well, of your children. This is what you pass to your children. You know people have known for 2000 years that your kids look a lot like you. Well it's because you must pass them something, some instructions that give them the eyes they have and the hair color they have and the nose shape they do. And the only way you pass it to them is in these sentences. That's it.

ROBERT KRULWICH: And to show you the true power of this molecule, we're going to start with one atom deep inside, and we pull back and you see it form its As and Ts and Cs and Gs and the classic double spiral. And then it starts the mysterious process that creates a healthy new baby. And the interesting thing is that every human baby, every baby born, is 99.9 percent identical in its genetic code to every other baby.

So the tiniest differences in our genes can be hugely important, can contribute to differences in height, physique, maybe even talents, aptitudes and can also explain what can break, what can make us sick.

Cracking the code of those minuscule differences in DNA that influence health and illness is what the Human Genome Project is all about. Since 1990, scientists all over the world in university and government labs, have been involved in a massive effort to read all three billion As, Ts, Gs, and Cs of human DNA.

They predicted it would take at least 15 years. That was partly because in the early days of the project, a scientist could spend years...an entire career trying to read just a handful of letters in the human genome. It took 10 years to find the one genetic mistake that causes cystic fibrosis. Another 10 years to find the gene for Huntington's disease. Fifteen years to find one of the genes that increase the risk for breast cancer. One letter at a time, painfully slowly...

ROBERT WATERSTON: One, two, three, four, five...

ROBERT KRULWICH: ...frustratingly prone to mistakes...

ROBERT WATERSTON (DNA mapping pioneer): ...Cs in a row.

NARRATOR: ...and false leads.

We asked Dr. Robert Waterston, a pioneer in mapping DNA, to show us the way it used to be done.

ROBERT WATERSTON: The original ladders for DNA sequence, we actually read by putting a little letter next to the band that we were calling and then writing those down on a piece of paper or into the computer after that. It's horrendous.

ROBERT KRULWICH: And we haven't mentioned the hardest part. This here, magnified 50,000 times is an actual clump of DNA, chromosome 17. Now if you look inside you will find, of course, hundreds of millions of As, and Cs, and Ts and Gs, but it turns out that only about one percent of them are active and important. These are the genes that scientists are searching for. So somewhere in this dense chemical forest are genes involved in deafness, Alzheimer's, cancer, cataracts. But where? This is such a maze scientists need a map. But at the old pace that would take close to forever.

ROBERT WATERSTON: C and then an A.

ROBERT KRULWICH: And then came the revolution. In the last ten years the entire process has been computerized. That cost hundreds of millions of dollars. But now, instead of decoding a few hundred letters by hand in a day, together these machines can do a thousand every second and that has made all the difference.

ROBERT COOK-DEEGAN (National Research Council): This is something that's going to go in the textbooks. Everybody knows that. Everybody, when the Genome project was being born, was consciously aware of their role in history.

ROBERT KRULWICH: Getting the letters out is...has been described as finding the blueprint of a human being, finding a manual for a human being, finding the code of the human being. What's your metaphor?

ERIC LANDER: Oh, golly gee. I mean, you can have very high falutin' metaphors for this kind of stuff. This is basically a parts list. Blueprints and all these fancy... It's just a parts list. It's a parts list with a lot of parts. If you take an airplane, a Boeing 777, I think it has like 100,000 parts. If I gave you a parts list for the Boeing 777 in one sense you'd know a lot. You'd know 100,000 components that have got to be there, screws and wires and rudders and things like that. On the other hand, I bet you wouldn't know how to put it together. And I bet you wouldn't know why it flies. Well we're in the same boat. We now have a parts list. That's what the human genome project is about is getting the parts list. If you want to understand the plane you have to have the parts list but that's not enough to understand why it flies. Of course you'd be crazy not to start with the parts list.

ROBERT KRULWICH: And one reason it's so important to understand all those parts, to decode every letter of the genome, is because sometimes, out of three billion base pairs in our DNA, just one single letter can make a difference.

Allison and Tim Lord are parents of two-year-old Hayden.

TIM LORD (Father of son with Tay Sachs): The two things that I think of the most about Hayden, which a lot of people got from him right from the beginning is that he was always, I thought, very funny. I mean he loved to smile and laugh and he just used to guffaw. And this was later when he was about a year old, he just found the funniest things hilarious. And so he and I would just crack each other up.

ROBERT KRULWICH: Hayden seemed to be developing normally for the first few months but Allison began to notice that some things were not quite right.

ALLISON LORD (Mother of son with Tay Sachs): I was very anxious all the time with Hayden. I sensed that something was not the same. I would see my friends changing the diaper of their child who was around the same age, their newborn, and see the physical movement, and the legs moving, and things like that, and Hayden didn't do that.

ROBERT KRULWICH: Doctors told them that Hayden was just developing a bit slowly. But by the time he turned a year old, it was clear something serious was wrong. He never crawled, he never talked, he never ate with his fingers and he seemed to be going backwards, not progressing.

TIM LORD: I remember the last time he laughed. And I took a trip with him out to pick up a suit because we were going to a wedding that night, and we came back and it was really windy, and he just loves to feel the wind, and so we had a great time. We came back and I propped him up right here on the couch and I was sitting next to him and he just kind of threw his head back and laughed, like, you know, what a fun trip, you know? And that the last time he was able to laugh. That's really hard.

ROBERT KRULWICH: It turned out that Hayden had Tay Sachs disease, a genetic condition that slowly destroys a baby's brain.

DR. EDWIN KOLODNY (NYU, Department of Neurology): What happens is the child appears normal at birth, and over the course of the first year begins to miss developmental milestones. So at six months a child should be turning over—a child is unable to turn over, to sit up, to stand, to walk, to talk.

ROBERT KRULWICH: Tay Sachs begins at one infinitesimal spot on the DNA ladder, when just one letter goes wrong. Say this cluster of atoms is a picture of that letter, a mistake here can come down to just four atoms. That's it. But since genes create proteins, that error creates a problem in this protein which is supposed to dissolve the fat in the brain. But now the protein doesn't work. So fat builds up, swells the brain, and eventually strangles and crushes critical brain cells. And all of this is the result of one bad letter in that baby' s DNA.

DR. EDWIN KOLODNY: In most cases it's a single base change. As we say, a letter difference.

ROBERT KRULWICH: One defective letter out of three billion, and no way to fix it.

TIM LORD: That's my boy.

ROBERT KRULWICH: Tay Sachs is a relentlessly progressive disease. In the year since his diagnosis, Hayden has gone blind. He can't eat solid food. It's harder and harder for him to swallow. He can't move on his own at all. And he has seizures as often as 10 times a day.

DR. EDWIN KOLODNY: For children with classical Tay Sachs Disease, there's only one outcome. And children die by the age of five to seven, sometimes even before age five.

ROBERT KRULWICH: As it happens, Tim Lord has an identical twin brother. When Hayden was diagnosed, that brother, Charlie, went to New York to be with Tim. And of course, Charlie called his wife Blyth to tell her the news. Blyth had been Allison's roommate in college and her best friend.

BLYTH LORD (Mother of daughter with Tay Sachs): Charlie told me that Hayden had Tay Sachs. He called me on the phone and he told me immediately what it was. I went up into the computer and looked it up and then just couldn't believe what I read.

ROBERT KRULWICH: Blyth and Charlie had a three-year- old daughter, Taylor, and a baby girl named Cameron. Cameron was healthy and happy except for one small thing.

BLYTH LORD: On the NTSAD Website it talks about typically between six and eight months is when the signs start coming, but one of the early signs is that they startle easily. And Hayden had always had a really heavy startle response. But we had noticed that Cameron had a comparable startle response. Not quite as severe but absolutely not like Taylor had had.

ROBERT KRULWICH: As soon as she saw that early warning sign on the Tay Sachs Website, Blyth went to get herself and Cameron tested.

CHARLIE LORD (Mother of daughter with Tay Sachs): It was another week. It was exactly a week until we got the final results on Cameron's blood work. And then the Tuesday before Thanksgiving we went into our pediatrician's office and he had the results, and we found out that night that Blyth was a carrier and that Cameron had Tay Sachs.

BLYTH LORD: He said...all he said was, "I'm sorry."

ROBERT KRULWICH: Tay Sachs is a very rare condition and it usually occurs in specific groups, like Ashkenazi Jews. And even then, the baby must inherit the bad gene from both parents. So even though there is a Tay Sachs test, the Lords had no reason to think they would be at risk. And yet incredibly, all four of them, Tim and Charlie and both their wives—all four were carriers. That was an unbelievably bad roll of the genetic dice.

TIM LORD: Charlie and I are incredibly close and have been all our lives. And when I think about him and Blyth having to go through this, it just seems really cruel. It just seems too much.

CHARLIE LORD: I had already geared myself up for being my brother's rock and I couldn't imagine having to help him and go through it myself.

ROBERT KRULWICH: For families like the Lords, and for everybody, the Human Genome project offers the chance to find out early if we're at risk for all kinds of diseases.

TIM LORD: I would like to see a really aggressive push to develop a test for hundreds of genetic diseases so that parents could be informed before they started to have children as to the dangers that face them. And I think it's within our grasp. Now that they've mapped the human genome, I mean, the information is there for people to begin to sort through. They're horrible, horrible, horrible diseases and if there's any way that you can be tested for a whole host of them and not have them affect a child, I think it's something that we have to focus on.

ROBERT KRULWICH: Hayden Lord died a few months before his third birthday. What makes this story especially hard to bear is we now know that a loss that huge—and it was a catastrophe, by any measure—started with a single error, a few atoms across, buried inside a cell.

Now, that something so small could trigger such an enormous result is a perspective that is incredibly frightening. Except that now geneticists have figured out how to see many of these tiny errors before they become catastrophes. When you think about that, that's an extraordinary thing, to spot a catastrophe when it's still an insignificant dot in a cell, which is the promise of the Human Genome Project. It is, first and foremost, an early warning system for a host of diseases which will give, hopefully, parents, doctors and scientists an advantage that we have never had before. Because when you can see trouble coming way, way before it starts you have a chance to stop it, or treat it. Eventually you might cure it.

And that's why, when Congress created the Human Genome Project in 1990, the challenge was to get a complete list of our As, Ts, Cs and Gs as quickly as possible, so the business of making tests, medicines, and cures could begin. They figured it would take about 15 years to decode a human being, and at the time that seemed reasonable.

Until this man, scientist, entrepreneur and speedboat enthusiast Craig Venter, decided that he could do it faster, much faster.

J. CRAIG VENTER: It's like sailing. Once you have two sailboats on the water going approximately in the same direction, they're racing. And science works very much the same way. If you have two labs remotely working on the same thing, one tries to get there faster, or better, higher quality, something different, in part because our society recognizes only first place.

ROBERT KRULWICH: Back in 1990, Venter was one of many government scientists painstakingly decoding proteins and genes. His focus was one protein in the brain.

J. CRAIG VENTER: It took ten years to get the protein and it took a whole year to get 1000 letters of genetic code.

ROBERT KRULWICH: For Venter that was way too slow.

So you're sitting there thinking there must be a better way when you're gazing out the window?

J. CRAIG VENTER: Yes, there had to be a better way.

ROBERT KRULWICH: And that's when he learned that someone had invented a new machine that could identify Cs and Ts and As and Gs with remarkable speed. And Craig Venter just loves machines that go fast.

J. CRAIG VENTER: I immediately contacted the company to see if I could get one of the first machines.

ROBERT KRULWICH: And here's how they work. Human DNA is chopped by robots into tiny pieces. These pieces are copied over and over again in bacteria and then tagged with colored dyes. A laser bounces light off each snip of DNA and the colors that it sees, represent individual letters in the genetic code. And these computers can do this 24 hours a day, every day.

J. CRAIG VENTER: So now you can see clearly the peaks.

ROBERT KRULWICH: Yup.

J. CRAIG VENTER: So there's just a blue one coming up so that's a C coming up. You could read this and you could write this all down.

ROBERT KRULWICH: So blue, yellow, red, red, yellow...

J. CRAIG VENTER: So that's C,G,T,T,A.

ROBERT KRULWICH: Then somehow all of these little pieces have to be put together again in the right order. Venter's dream was to have hundreds of new machines at his fingertips so he quit his government job and formed a company he called Celera Genomics. Celera from the Latin word celerity, meaning speed. And this is what he built.

Oh, my Lord. And you know why that's interesting? There's almost nobody here.

J. CRAIG VENTER: Yeah, it's all automated.

ROBERT KRULWICH: So, who is this guy and why is he such a bulldog for speed?

Craig Venter grew up in California, left high school and spent a year as a surfing bum—on the beach by day and a stock boy at Sears by night. He was, inevitably, drafted, went to Vietnam with the Navy. That's him way over there on the left. He was eventually assigned to a Naval hospital in Danang during the Tet offensive when Americans were taking very heavy casualties. At 21, he was in the triage unit, where they decide who will live and who will die.

When you're young and you see a lot of people die and they all could be you, do you then feel that you sort of owe them cures? Cures that they'll never get? Or am I over-romanticizing?

J. CRAIG VENTER: Well, the motivations become complex. That's certainly a part of it. Also I think surviving the year there was...it sort of puts things in perspective, I think. If you're not in that situation, you can never truly have it in perspective.

ROBERT KRULWICH: You hear time...you hear ticking?

J. CRAIG VENTER: Yes. But also I feel that I've had this tremendous gift for all these years since I got back in 1968, and I wanted to make sure I did something with it.

ROBERT KRULWICH: In the spring of 1998, Venter announced that he and his company were going to sequence all three billion letters of the human genome in two years. Remember, the government said it would take 15.

J. CRAIG VENTER: There was a lot of arrogance that went with that program. They were going to do it at their pace. And a lot of the scientists, you know, if they were really being honest with you, would tell you that they planned to retire doing this program. That's not what we think is the right way to do science, especially science that affects so many people's lives.

ROBERT COOK-DEEGAN: Craig is a high testosterone male who has...he just loves being an iconoclast. Right? He loves rattling people's cages and he's done that consistently in the genome project.

ROBERT KRULWICH: Craig Venter's announcement that his team would finish the entire genome in just two years galvanized everybody working on the public project. Now they were scrambling to keep up.

HUMAN GENOME PROJECT STAFF MEMBER: There are some limitations. We don't think we can get this thing to go any faster at the moment without throwing a lot more robotics at it. The arm physically takes twenty seconds to...

ROBERT KRULWICH: Francis Collins, the head of the Human Genome Project, was determined that Celera was not going to beat his teams to the prize. He made a dramatic decision to try to cut five full years off the original plan.

FRANCIS COLLINS: When the major Genome Centers met and agreed to go for broke here, I don't think there was anybody in the room that was very confident we could do that. I mean you could sit down with a piece of paper and make projections, if everything went really well, that might get you there, but there were so many ways this could have just run completely off the track.

ROBERT KRULWICH: At MIT they decided to try to scale up their effort 15-fold and that meant a major change in their usual academic pace.

LAUREN LINTON (MIT): We basically had a goal since March to get to a plate-a-minute operation from womb to tomb all the way through.

ROBERT KRULWICH: In the fall of 1999, representatives from the five major labs come to check out Eric Lander's operation. All the big honchos in the Human Genome Project are here: scientists from Washington University in St Louis, Baylor College of Medicine in Texas, the Department of Energy. She's from the Sanger Center in England. If they want to finish the genome before Craig Venter, these folks have to figure out how to outfit their labs with a lot of new and fancy and unfamiliar equipment. And they've got to do it fast.

LAUREN LINTON: So we'll have to runs some sort of a conduit.

ROBERT KRULWICH: At MIT a different crate is arriving almost daily.

MIT STAFF RESEARCHER ONE: It's like Christmas, everyone unwraps something.

ROBERT KRULWICH: Just like a bad Christmas present, assembly is required. And the instructions are of course not always clear.

MIT STAFF RESEARCHER TWO: Oh, no, the magnet plates stick to each other?

MIT STAFF RESEARCHER THREE: ...plus or minus three feet.

ERIC LANDER: Since one's on the cutting edge...I guess they always call it "the bleeding edge," right? Nothing really is working as you expect. All the stuff we're doing will be working perfectly as soon as we're ready to junk it.

ROBERT KRULWICH: The MIT crew is particularly excited about their brand new three-hundred-thousand-dollar state-of-the-art DNA purifying machine.

MIT STAFF RESEARCHER FOUR: Why don't you turn it on.

MIT STAFF RESEARCHER THREE: All right, maiden voyage. It didn't ask me for a password. That's good.

MIT STAFF RESEARCHER FOUR: Are you supposed to get the yellow light right away?

ROBERT KRULWICH: I don't think the blinking light is a good sign.

ERIC LANDER: It's sort of like flying a very large plane and repairing it while you're flying. You want to figure out what went wrong. And you also realize that you're spending, oh, tens of thousands of dollars an hour. So you feel under a little pressure to sort of work this out as quickly as you can.

ROBERT KRULWICH: So he calls the customer service line. And of course he's put on hold. So he waits. And he waits. And he waits. Anyway, it turns out that the three-hundred-thousand-dollar machine does have one tiny little valve that's broken, and so it doesn't work.

ERIC LANDER: You never know whether the problem is due to some robot, some funky little biochemistry, some chemical that you've got that isn't really working. And so it's incredibly complicated.

MIT STAFF RESEARCHER FIVE: So we have a test transformation where we transform a tenth of our ligation.

MIT STAFF RESEARCHER SIX: And add SDS to lyse the phage.

MIT STAFF RESEARCHER SEVEN: And all of our thermo-cyclers have three-eighty-four-well plates.

MIT STAFF RESEARCHER EIGHT: So if you basically determine where your 96 well...plate wells were on this three hundred eighty-four-well plate and give them each a different run-module...

FRANCIS COLLINS: When you try to ramp something up, anything that's the slightest bit kludgy suddenly becomes a major bottleneck.

MIT STAFF RESEARCHER NINE: We talked about doing a full-up test today and we weren't quite feeling good about doing that yet.

FRANCIS COLLINS: There was a considerable sense of white knuckles amongst all of us, 'cause here we'd made this promise. We're on the record here saying we're going to do this. And things weren't working. The machines were breaking down. It's got to work now. The time is running out.

ROBERT KRULWICH: It took a while, but the government teams finally hit their stride.

FRANCIS COLLINS: The fall of that year was really sort of the determining time. The centers really proved their mettle. And every one of them began to catch this rising curve and ride it. And we began to see data appearing at prodigious rates. By early 2000, a thousand base pairs a second were rolling out of this combined enterprise, seven days a week, 24 hours a day, a thousand base pairs a second. Then it really starts to go.

ROBERT KRULWICH: And those thousands of base pairs poured out of the university labs directly onto the Internet, updated every night. It's available for anybody and everybody, including, by the way, the competition.

Celera admits they got lots of data directly from the government. And Tony White, who runs the company that owns Celera, says "Why not?"

TONY WHITE: That's publicly available data. I'm a taxpayer. Celera's a taxpayer. You know, it's publicly...why should we be excluded from getting it? I mean, again, are they creating it to give it to mankind except Celera? Is that the idea? It isn't about us getting the data. It's about this academic jealousy. It's about the fact that our data, in combination with theirs, gives us a perceived, unfair advantage over this so-called "race."

ERIC LANDER: If they want to race us, that's their business.

ROBERT KRULWICH: Of course they do. Don't they?

ERIC LANDER: I suppose they may.

ROBERT KRULWICH: I suspect strongly they may.

ERIC LANDER: Our job is to get that data out there so everybody can go use it.

ROBERT KRULWICH: Since Celera was sequencing the genome with private money, some critics wondered, "Why should the government put so much cash into the exact same research?"

ERIC LANDER: In the United States, we invested in a national highway system in the 1950s. We got tremendous return for building roads for free and letting everybody drive up and down them for whatever purpose they wanted. We're building a road up and down the chromosomes for free. People can drive up and down those chromosomes for anything they want to. They can make discoveries. They can learn about medicine. They can learn about history. Whatever they want. It is worth the public investment to make those roads available.

ROBERT KRULWICH: But wait a second - What I really want to know is, if you are making a roadmap of a human being, which human beings are we mapping? I mean, humans come in so many varieties, so whose genes exactly are we looking at?

ERIC LANDER: It's mostly a guy from Buffalo and a woman from Buffalo. That's because the laboratory...

ROBERT KRULWICH: Whoa, whoa. An anonymous couple from Buffalo?

ERIC LANDER: No, they're not a couple. They're not a couple. They've never met.

ROBERT KRULWICH: Oh, I see.

ERIC LANDER: The laboratory was a laboratory in Buffalo. And so they put an ad in Buffalo newspapers and they got random volunteers from Buffalo. They got about 20 of them, and chose at random this sample and that sample and that sample. So nobody knows who they are.

ROBERT KRULWICH: And what about Celera? Whose DNA are they mapping?

They also got a bunch of volunteers, around 20, and picked five lucky winners.

J. CRAIG VENTER: We tried to have some diversity in terms of...we had an African American, somebody of self-proclaimed Chinese ancestry, two Caucasians and a Hispanic. And so some of the volunteers were here on the staff, and...

ROBERT KRULWICH: I have to ask 'cause everybody does. Are you one of them?

J. CRAIG VENTER: I am one of the volunteers, yes.

ROBERT KRULWICH: Oh. Do you know whether you, whether you are one of the winners?

J. CRAIG VENTER: I have a pretty good idea, yes. Uh, but, I can't disclose that. Because it doesn't matter.

ROBERT KRULWICH: Well if you're the head of the company and you're watching the decoding of "moi," that has a little Miss Piggy quality to it.

J. CRAIG VENTER: Well, any scientist that I know would love to be looking at their own genetic code. I mean, how could you not want to and work in this field?

ROBERT KRULWICH: Well, I don't know, I don't work in this field. But I do wonder, could any small group, I mean, could that guy from Buffalo, could he really be a stand-in for all human kind? Hasn't it been drummed into us since birth that we are all different, each and every one of us completely unique? We certainly look different. People come in so many shapes and colors and sizes the DNA of these humans has got to be significantly different from the DNA of this human. right?

ERIC LANDER: The genetic difference between any two people: one tenth of a percent. Those two, and any two people on this planet are 99.9 percent identical at the DNA level. It's only one letter in a thousand difference.

ROBERT KRULWICH: And if I were to bring secretly into another room, a black man, an Asian man, and a white man, and show you only their genetic code, could you tell which one was the white...?

ERIC LANDER: Probably not.

What's going on? Well, it tells us that, first, as a species we're very, very closely related. 'Cause any two humans being 99.9 percent identical means that we're much more closely related than any two chimpanzees in Africa.

ROBERT KRULWICH: Wait, wait. Wait, wait, wait, wait. You mean if two Chimpanzees are swinging through the forest and you look at the genes of Chimp A and the genes of Chimp B...

ERIC LANDER: Average difference between those chimps is four or five times more than the average difference between two humans that you'd pluck off this planet.

ROBERT KRULWICH: Because we're such a young species?

ERIC LANDER: That's right. See, the thing is, we are the descendants of a very small founding population. Every human on this planet goes back to a founding population of perhaps 10 or 20 thousand people in Africa about 100 thousand years ago. That little population didn't have a great deal of genetic variation. And what happened was, it was successful. It multiplied all over the world, but in that time relatively little new genetic variation has built up. And so we have today on our planet about the same genetic variation that we walked out of Africa with.

ROBERT KRULWICH: So people are incredibly similar to each other. But not only that. It turns out we also share many genes with...well...everything.

Fifty percent of the genes in a banana are in us?

ERIC LANDER: How different are you from a banana?

ROBERT KRULWICH: I feel...and I feel I can say this with some authority...very different from a banana.

ERIC LANDER: You may feel different from a banana...

ROBERT KRULWICH: I eat a banana, but I have never...

ERIC LANDER: Look, you've got cells, you've got to make those cells divide. All the machinery for replicating your DNA, all the machinery for controlling the cell cycle, the cell surface, for making nutrients—all that's the same in you and a banana.

Deep down, the fundamental mechanisms of life were worked out only once on this planet, and they've gotten reused in every organism. The closer and closer you get to a cell the more you see a bag with stuff in it and a nucleus, and most of those basic functions are the same. Evolution doesn't go reinvent something when it doesn't have to.

Take baker's yeast. Baker's yeast we're related to one and a half billion years ago. But even after one and a half billion years of evolutionary separation, the parts are still interchangeable for lots of these genes.

ROBERT KRULWICH: Now, does that mean—I just want to make sure if I understand this right. Does that mean when you look through those things that all the Cs and the As and the Ts and the Ts and the Gs...are you seeing the exact same letter sequences in the exact same alignment? When you look at the yeast and you look at the person, is it C-C-A-T-T-T?

ERIC LANDER: Sometimes. It's eerie. The gene sequence is almost identical. There are some genes, like ubiquitin, that's 97percent identical between humans and yeast, even after a billion years of evolution.

ROBERT KRULWICH: Well, with a name like that it's got to be.

ERIC LANDER: Well, yeah, but you've got to understand that deep down we are very much partaking of that same bag of tricks that evolution's been using to make organisms all over this planet.

ROBERT KRULWICH: It seems incredible but all this information about evolution, about our relationship to each other and to all living things, it's all right here in this monotonous stream of letters. And as the Human Genome Project progressed and hit high gear the pace of discovery quickened. Once they got fully automated, it wasn't long before Lander and Collins and all the other public project teams had reason to celebrate.

FRANCIS COLLINS: I'm Francis Collins, the director of the National Human Genome Research Institute and we're happy to be here together to have a party today.

ROBERT KRULWICH: By November of 1999, they had reached a major milestone. In a five-way awards ceremony, hooked up by satellite, the major university teams announced they had finished a billion base pairs of DNA, a third of the total genome.

ERIC LANDER: Have we got everybody? I would like to propose a toast. A billion base pairs, all on the public Internet, available to anybody in the world. It's an incredible achievement. It hasn't been completely painless. And because I know everybody in this room is living and breathing and thinking every single moment in the day, about how to make all this happen, how we can hit full scale I want to be sure you realize what a remarkable thing we pulled off. I hope you also know that this is history. Whatever else you do in your lives, you're part of history. We're part of an amazing effort on the part of the world to produce this. And this isn't going to be like the moon, where we just visit occasionally. This is going to be something that every student, every doctor uses every day in the next century and the century after that. It's something to tell your kids about. Something to tell your grandkids about. It's something you should all be tremendously proud of. And I'm tremendously proud of you. A toast to this remarkable group, to the work we've done, to the work ahead. Hear, hear.

ROBERT KRULWICH: Everybody here is hoping the Genome Project will help cure disease, and the sooner it's done, the better for all of us. But there's something more than idealism, more than even pride that's driving this race to finish the genome. And that is the knowledge that with every day that passes more and more pieces of our genome are being turned into private property by way of the US Patent Office.

PATENT OFFICE STAFF MEMBER: I say a property...

ROBERT KRULWICH: The office is inundated with requests for patents for every imaginable invention, from Star Wars action figures, to jet engines. And here along with all those gizmos, are requests for patents for human genes, things that exist naturally in every one of us. How is this possible?

TODD DICKINSON (Former Director, US Patent Office): We regard genes as a patentable subject matter as we regard almost any chemical. We have issued patents on a number of compounds, a number of compositions that are found in the human body. For example the gene that encodes for insulin has been patented. And that now is used to make almost all of the insulin that is made so people's lives are being saved today. Diabetics' lives are better.

As a matter of fact if we ruled out every chemical that is found in the human body, there would be an awful lot of inventions that would not be able to be protected.

ROBERT KRULWICH: Generally, to patent an invention, you've got to prove that it's new and useful. But a few years ago, critics said the patent office wasn't being tough enough. So applicants would say, "Well, here's a brand new sequence of As, Cs, Ts and Gs right out of our machines. That's new. Now useful? What were they going to be used for? "Well, they were kind of vague about use," says Eric Lander.

ERIC LANDER: The sort of thing that people used to do then was they would say, "It could be used as a probe to detect itself." It's a trivial use. I mean, it's like saying, "I could use this new protein as packing peanuts to stuff in a box." I mean, it's true. It takes up space.

ROBERT KRULWICH: Wouldn't the patent examiner say, "That's not useful."

ERIC LANDER: No, no, no. You see the patent guidelines are very unclear. I don't object to giving somebody that limited-time monopoly when they've really invented a cure for a disease, some really important therapy. I do object to giving a monopoly when somebody has simply described a couple hundred letters of a gene, has no idea what use you could have in medicine. Because what's going to happen is you've given away that precious monopoly to somebody who's done a little bit of work. And then the people who want to come along and do a lot of work, to turn it into a therapy, well they've got to go pay the person who already owns it. I think it's a bad deal for society.

ROBERT KRULWICH: It takes at least two years for the patent office to process a single application, so right now, there are about 20,000 genetic patents waiting for approval. All of them are in limbo.

This can cause problems for drug companies who are trying to work with genes to cure disease. I'm a company trying to do work on this, this, and this rung of the ladder because I think I can maybe develop a cure for cancer right here, just for the sake of argument. But of course I have to worry that somebody owns this space.

ERIC LANDER: You have to worry a lot that this region here, that you're working on, that might cure cancer has already been patented by somebody else and that patent filing is not public. And so you're living with the shadow that all of your work may go for naught.

ROBERT KRULWICH: Because one day the phone rings and says "Sorry you can't work here. Get off my territory."

ERIC LANDER: That's right.

ROBERT KRULWICH: Or, "You can work here, but I'm going to charge you $100,000 a week." Or "You can work here and I'll charge you a nickel but I want 50 percent of whatever you discover or any of it."

ERIC LANDER: And the problem here is...it's even worse because many companies don't start the work whenever there's a cloud over who owns what. If there's uncertainty...companies would rather be working someplace where they don't have uncertainty. And therefore, I think work doesn't get done because of the confusion over who owns stuff.

ROBERT KRULWICH: Supporters of patents say they're a crucial incentive for drug companies. Drug research is phenomenally expensive, but if a company can monopolize a big discovery with a patent, it can make hundreds of millions of dollars.

Research scientists suddenly find themselves in an unfamiliar world ruled by big money.

SHELDON KRIMSKY (Science Policy Analyst, Tufts University): Every scientist who does research is now being looked upon as a generator of wealth, even if that person is not interested in it. If they sequence some DNA, that could be patentable material. So whether the scientist likes it or not, he or she becomes an entrepreneur just by virtue of doing science.

ROBERT KRULWICH: Craig Venter is first a scientist, but he has made the leap from academia into the business world. Let me talk about the business of this. Do you consider yourself a businessman?

J. CRAIG VENTER: No. In fact I still sort of bristle at the term for some reason. But my philosophy is we would not get medical breakthroughs in this country at all if it wasn't done in a business setting. We would not have new therapies if we didn't have a biotech and pharmaceutical industry.

ROBERT KRULWICH: But are they...if you bristle at the word businessman, that might be because in some part of your soul, you may think that the business of science and the business of business are fundamentally incompatible for one simple reason—that the business has to sell something and the science has to learn or teach something.

J. CRAIG VENTER: I think I bristle at it because it's used as an attack, used as a criticism. In this case, if the science is not spectacular, if the medicine is not spectacular, there will be no profits.

ROBERT KRULWICH: Venter was given three hundred million dollars to set up Celera, and his investors are expecting something in return. But how can they profit from the genome?

At the moment, the company is banking on pure computer power. This is Celera's Master Control. Twenty-four hours a day, technicians monitor all the company's major operations, including the hundreds of sequencers that are constantly decoding our genes.

And they oversee Celera's main source of income, a massive Website where, for a fee, you can explore several genomes, including those of fruit flies, mice and of course, humans. What all this adds up to is something like a big browser, a user-friendly interface between you and your genes.

TONY WHITE (CEO, Applera Corporation): Our business is to sell products that enable research. That's essentially what we do. So we're used to selling the picks and the shovels to the miners. Tools to interpret the human genome and other related species are merely more products along the same genre. They just happen to be less tangible than a machine.

ROBERT KRULWICH: So Celera's business plan is to gather information from all kinds of creatures, put it together and sell their findings to drug companies or universities or whomever. But it's the selling part, selling scientific information, that makes some scientists very uncomfortable.

SHELDON KRIMSKY: This is a big change in the ethos of the scientific community, which is supposedly...it was built upon the idea of communitarian values of the free and open exchange of information. The fundamental idea that when you learn something, you publish it immediately, you share it with others. Science grows by this communitarian interest of shared knowledge.

TONY WHITE: I think, "Why doesn't Pfizer give away their drugs? They could help a lot more people if they didn't charge for them."

CELERA STAFF MEMBER: At what point is free really free?

ROBERT KRULWICH: Tony White has absolutely no problem with making money from the human genome.

TONY WHITE: I hope we have a legal monopoly on the information. I hope our product is so good, and so valuable to people, that they feel that it's necessary to come through us to get it.

Anybody who wants to can build all the tools that we're going to build. Whether or not they will choose to is a different matter.

ROBERT KRULWICH: Now which is the better business to be in, do you think, the landlord business, or this, "You subscribe, and I'll give you some information about anything you want," business?

ERIC LANDER: They're both lousy businesses.

ROBERT KRULWICH: They're lousy?

ERIC LANDER: They're lousy businesses by comparison with the real business. Make drugs. Actually make molecules that cure people.

ROBERT KRULWICH: Curing people is the whole point, right?

But if there is one thing that the Human Genome Project has taught us, it's that finding cures is a whole lot harder than simply reading letters of DNA.

Take, for example, the case of little Riley Demanche. At two months, Riley appears to be a perfectly healthy baby boy. But he's not. When Riley was just 13 days old, Kathy Demanche got the call that every parent dreads.

KATHY DEMANCHE (Mother of a son with cystic fibrosis): My pediatrician called on a Thursday evening and he said, "I need to talk to you about the baby." He said, "Are you sitting down?" And I'm like, "Yeah." And that really surprised me. And he said, "Are you holding the baby?" Because he didn't want me to drop the baby, obviously. And he said, "The tests came through, and Riley tested positive to cystic fibrosis."

And I was in shock.

ROBERT KRULWICH: As Kathy and her husband would soon learn, cystic fibrosis, CF for short, attacks several organs of the body, but especially the lungs. Its victims suffer from chronic respiratory infections. Half of all CF patients die before the age of 30.

DAVID WALTZ (Children's Hospital, Boston): Sounds good.

KATHY DEMANCHE: Good.

DAVID WALTZ: I think we can be hopeful that their child will grow up to have a normal and healthy, happy and long life. But at the present time, I don't have any guarantees about that.

KATHY DEMANCHE: Someone had asked me, "Are you prepared to bury your son at such a young age? Whether it's four or forty?" And he was 17 days old when that happened. And I said, "I've had him for 17 days. I wouldn't trade those 17 days."

ROBERT KRULWICH: Finding the genetic defect that causes CF was big news back in 1989.

TAPE OF NEWS ANCHOR: Medical researchers say they have discovered the gene which is responsible for cystic fibrosis, the most common inherited fatal disease in this country.

TAPE OF ROBERT DRESSING: We are going to cure this disease.

ROBERT KRULWICH: A lot of people expected the cure to arrive any day. It didn't.

Francis Collins, now head of the government's Genome Project, led one of the teams that discovered the CF gene.

FRANCIS COLLINS: We still have not seen this disease cured or even particularly benefited by all of this wonderful molecular biology. CF is still treated pretty much the way it was 10 years ago. But that is going to change.

ROBERT KRULWICH: The original hope was that babies like Riley could be cured by gene therapy, medicine that could provide a good working copy of a broken gene. But attempts at gene therapy have hardly ever worked. They remain highly controversial. So if there's going to be an effective treatment for Riley, instead of fixing his genes, we're going to take a look—and this is new territory—at his proteins.

ROBERT KRULWICH: What do proteins do?

J. CRAIG VENTER: When you look at yourself in the mirror, you don't see DNA. You don't see RNA. You see proteins and the result of protein action. So that's what we are physically composed of.

ROBERT KRULWICH: So it's not a Rogers and Hammerstein thing, where one guy does the tune and the other guy does the lyrics. This is a case where the genes create the proteins and the proteins create us?

J. CRAIG VENTER: That's right. We are the accumulation of our proteins and protein activities.

ROBERT KRULWICH: A protein starts out as a long chain of different chemicals, amino acids. But unlike genes, proteins won't work in a straight line.

FRANCIS COLLINS: Genes are effectively one-dimensional. If you write down the sequence of A, C, G, and T, that's kind of what you need to know about that gene. But proteins are three-dimensional. They have to be because we're three-dimensional and we're made of those proteins. Otherwise, we'd all sort of be linear, unimaginably weird creatures.

ROBERT KRULWICH: Here's part of a protein. Think of them as tangles of ribbon. They come in any number of different shapes. They can look like this. Or like this. Or this. The varieties are endless.

But when it's created, every protein is told, "Here is your shape." And that shape defines what it does, tells all the other proteins what it does. And that's how they recognize each other when they hook up and do business. In the protein world, your shape is your destiny.

FRANCIS COLLINS: They have needs and reasons to want to be snuggled up against each other in a particular way. And actually a particular amino acid sequence will almost always fold in a precise way.

ROBERT KRULWICH: Should I think origami-like? I mean, should I think folding and then...

FRANCIS COLLINS: It's very elegant, very complicated. And we still do not have the ability to precisely predict how that's going to work. But obviously it does work.

ROBERT KRULWICH: Except, of course, if something does go wrong. And that's what happened to baby Riley. Riley has an tiny error in his DNA. Just three letters out of three billion are missing. But because of that error, he has a faulty gene. And that faulty gene creates a faulty, or misshapen protein. And just the slightest little changes in shape and boom. The consequences are huge.

Because it is now misshapen, and a key protein that is found in lung cells, in fact in many cells, can't do its job.

So let's take a look at some real lung cells. We'll travel in.

This is the lining, or the membrane, of a lung cell and here is how the protein is supposed to work. The top of your screen is the outside of a cell; the bottom of the screen, the inside of the cell, of course. And our healthy protein is providing a kind of chute so that salt can enter and leave the cell. Those little green bubbles, that's salt. And as you see here, the salt is getting through.

But if the protein is not the right shape, then it's not allowed into the membrane. It can't do it's job. And without that protein, as you see here, salt gets trapped inside the cell. And that triggers a whole chain of reactions that makes the cell surface sticky and covered with thick mucus. That mucus has to be dislodged physically.

Riley's family is learning to loosen the mucus that may develop in his lungs, and fight infections with antibiotics. But what the doctors and the scientists would love to do is, if they can't fix baby Riley's genes, then maybe there's some way to treat Riley's misshapen protein and restore the original shape. Because if you could just get them shaped right, the proteins should become instantly recognizable to other proteins and get back to business.

But look at these things. How would we ever learn to properly fold wildly, multi-dimensional proteins? It may be doable, but it won't be easy.

ERIC LANDER: The genome project was a piece of cake compared to most other things, because genetic information is linear. It goes in a simple line up and down the chromosome. Once you start talking about the three-dimensional shapes into which protein chains can fold and how they can stick to each other in many different ways to do things, or the ways in which cells can interact, like wiring up in your brain, you're not in a one-dimensional problem anymore. You're not in Kansas anymore.

ROBERT KRULWICH: And as scientists head into the world of proteins, they're looking very closely at patients like Tony Ramos.

Tony has cystic fibrosis, but it's not the typical case. CF almost always develops in early childhood. Tony didn't have any symptoms until she was 15.

TONY RAMOS (Cystic fibrosis patient): I started having a cough. And then we kept thinking I was catching a lot of colds. And my stepmother thought, "That's not right." So I started going to doctors trying to figure it out and went through a lot of tests because I don't fit the profile. Tuberculosis, walking pneumonia, you know, test after test.

ROBERT KRULWICH: At the time of her diagnosis, Tony's family was told she might not survive beyond her twenty-first birthday. She is now in her mid-forties, but her CF is worsening. Two or three times a year, she does have to be admitted to the hospital to clean out her lungs.

TONY RAMOS: They were always doing some little funky study to help the cause because we're not the normal...you know...there's not a whole lot of us. I know that they don't know why. And it's the big question mark. And hopefully, research will keep going to figure it out.

ROBERT KRULWICH: Here's the question. Tony was born with a mistake in the same gene as baby Riley, and yet, for some reason, when Tony was a baby she didn't get sick. Why? And now that she is sick, she hasn't died. Why? What does Tony have that the other CF patients don't have?

Dr. Craig Gerard believes the answer lies in her genes, in her DNA.

CRAIG GERARD (Children's Hospital, Boston): No gene acts in isolation. It is always acting as a part of a larger picture. And there can therefore be other genes which compensate.

ROBERT KRULWICH: Could it be that Tony has some other genetic mutations, good mutations that are producing good proteins that kept her healthy for 15 years? That are keeping her alive right now?

CRAIG GERARD: In my opinion there are genes that are allowing her to have a more beneficial course, if you will, than another patient.

ROBERT KRULWICH: Dr. Gerard is searching for the special ingredient in Tony. If it turns out she has one or two good proteins that are helping her, maybe we could bottle them and use them to help all CF patients like baby Riley.

No one can predict Riley's future, or to what extent CF will affect his life. But now that we're getting the map of our genes, we'll be able to take the next big step.

Because what genes do, basically, is they make proteins.

I get the sense that everybody is getting out of the gene business and suddenly going into this new business I hear about, called the protein business. There's even a new name, instead of genome, I'm hearing this other name...

ERIC LANDER: The proteome.

ROBERT KRULWICH: The proteome. What's that?

ERIC LANDER: Well, the genome is the collection of all your genes and DNA. The proteome is the collection of all your proteins. See, what's happening is we're realizing that if we wanted to understand life, we had to start systematically at the bottom and get all the building blocks. The first building blocks are the DNA letters. From them we can infer the genes. From the genes, we can infer the protein products that they make that do all the work of your cell. Then we've got to understand what each of those proteins does, what its shape is, how they interact with each other, and how they make kind of circuits and connections with each other. So in some sense, this is just the beginning of a very comprehensive, systematic program to understand all the components and how they all connect with each other.

ROBERT KRULWICH: All the components and how they connect? But how many components are there? How many genes and how many proteins do we have?

ERIC LANDER: The real shock about the genome sequence was that we have so many fewer genes than we've been teaching our students. The official textbook answer is, "The human has 100,000 genes." Everybody's known that since the early 1980s. The only problem is it's not true. Turns out we only have 30,000 or so genes.

ROBERT KRULWICH: Thirty thousand genes? That's it? Not everybody agrees with this number but that's about as many as a mouse! Even a fruit fly has 14,000 genes.

ERIC LANDER: That's really bothersome to many people, that we only have about twice as many genes as a fruit fly, because we really like to think of ourselves as a lot more than twice as complex.

ROBERT KRULWICH: Well, don't you?

ERIC LANDER: I certainly like to think of myself that way. And so it raises two questions. Are we really more complex?

ROBERT KRULWICH: You show me the fruit fly that can compose like Mozart, and then I'll obviously...

ERIC LANDER: Yeah, well, show me the human that can fly, right? So?

ROBERT KRULWICH: All right.

ERIC LANDER: We all have our talents, right?

ROBERT KRULWICH: I suppose we do. But as it happens, we have lots of genes that are virtually identical in us and fruit flies. But happily, our genes seem to do more.

So, let's say that I am a fruit fly. One of my fruit fly genes may make one and two slightly different proteins. But now I'm a human, and the very same gene in me might make one, two, three, four different proteins. And then these four proteins could combine and build even bigger and more proteins.

ERIC LANDER: Turns out that the gene makes a message, but the message can be spliced up in different ways. And so a gene might make three proteins or four proteins, and then that protein can get modified. There could be other proteins that stick some phosphate group on it, or two phosphate groups. And in fact all of these modifications to the proteins could make them function differently. So, while you might only have, say 30,000 genes, you could have 100,000 distinct proteins. And when you're done putting all the different modifications on them, there might be a million of them. Scary thought.

ROBERT KRULWICH: So, starting with the same raw ingredients, the fruit fly goes, "hm, phht, hm, phht, hm, phht," but the human, by somehow or other being able to arrange all the parts in many different ways, can produce melodies perhaps.

ERIC LANDER: Yes. Although we're not that good at hearing the melodies yet. We can...one of the exciting things about reading the genome sequence now is we're getting a glimpse at that complexity of the parts, and how it's a symphony rather than a simple tune. But it's not that easy to just read the sheet music there and hear the symphony that's coming out of it.

ROBERT KRULWICH: Okay, so it's not just the number of genes, it's all the different proteins they can make and then the way those proteins interact. And to figure out all those interactions and how they affect health and disease, that's going to keep scientists very busy for the next few decades.

But of course, before the research can begin in earnest, they first have to complete the parts list—all the genes.

And by the spring of 2000, both sides—the public labs and Celera—they were in hyperdrive—each camp madly trying to be the first to reach the finish line and get all three billion letters.

GENE MYERS (Vice President, Informatics Research, Celera): The pace of things and the magnitude of things was really incredible. I mean, I would remember coming in and just having this really gripping feeling in my gut, I mean just an intense kind of, "Oh, my God. Am I up to this?"

ROBERT COOK-DEEGAN: You know, whoever has this reference sequence of the Human Genome out there in the world first, they're going to be famous. They're going to be on the front page of the New York Times and a lot more than that, for a long time. They're going to be, you know, celebrities. And you know, when that's going on, it's not unreasonable that people are going to reach for that star and try to get there before the other person.

TONY WHITE: I thought the really intense competition in this world was among businesses where there was a profit motive. I now find that we are pikers in the business world, compared to the academic competition that exists out there. And I'm beginning to understand why. Because their currency is publication. Their currency is attribution. And their next funding comes from their last victory.

ROBERT COOK-DEEGAN: I think we're all better off for the fact that there is this competition. What you want is a system that gets people riled up and trying to do something faster, better and cheaper than the next guy.

GENE MYERS: The environment at Celera was really intense, and it reminded me of finals week at Cal Tech. And there's a tradition at Cal Tech that on the very first day of finals week, The Ride of the Valkyries is played at full blast. And so, I thought, "Well, since every week feels like it's finals week here, why don't I play The Ride, and see what happens."

So we got a whole bunch of Viking hats and we end up buying Nerf® bows, okay? Since we're Nordic Valkyrians. And the next week, we're shooting each other. And we go, "You know, there's something not right about this." So we decided the next week that we'd start doing raiding parties, then raid some of the other teams.

Unbeknownst to us, they had been preparing themselves. They had little beanie hats. Okay, and their own Nerf® weapons. Then the war started.

It's just a release. It's a way of kind of dealing with the pressure, I think. We all ran around like crazy for five or ten minutes, and got a little physical exercise, and had a few laughs. And then we're ready to really go after it.

ROBERT KRULWICH: The Wagner seems to be working.

Output at Celera continues at a relentless pace. Venter insists that the urgency stems not only from a desire to beat the government project, but the firm belief that what's coming out of these machines—all the As, Cs, Ts, and Gs—will have a profound impact on all our lives.

J. CRAIG VENTER: It's a new beginning in science and until we get all that data, that can't really take place. Anybody that has cancer, anybody that has a family member with a serious disease...this data and information offers them tremendous hope that things could change in the future.

ERIC LANDER: In the past, if you wanted to explain diabetes, you always had to scratch your head and say, "Well, it might be something else we've never seen before." But knowing that you've got the full parts list radically changes biomedical research, because you can't wave your hands and say, "It might be something else." There is no something else.

ROBERT KRULWICH: In the past, finding the genes that cause a disease was a painstakingly slow process. But with the completion of a list, it should be much easier to make a direct connection from disease to gene.

But how? Well, let's say I'm looking for a gene that causes something...we'll make it male-pattern baldness. How would I go about that?

Well, I'd want to get a bunch of bald guys.

So here are three bald guys and take their blood and look at their DNA. Now, I'll take three guys with lots of hair, and here's their DNA. And what if the bald guys all share a particular spelling right here, in this spot, which we call the bald spot. And at the same spot, you notice the hairy guys have...you see that? A different spelling.

So is this the gene that causes baldness? Maybe, but probably not. This could be a coincidence

So, how do I improve my chances of finding the specific spelling difference that relates to baldness? It would help if I knew that the bald guys and the hairy guys had really similar DNA, except for the genes I suspect may make them either bald or hairy.

Where do I find guys who are very, very similar, with a few exceptions? A family, right? If there were brothers and fathers and sons and cousins, for instance, who share lots of genes. So let's say these three guys are brothers—astonishing similarity really in the face. But notice that one of them is hairy and two are bald.

Whatever is making this one different should stand out when you compare their genes. And the same for these guys. There's a difference, clearly, in the photos, but that difference may turn up in the genes.

You could do the same thing for any disease you like. So, if I could comb through the DNA of lots of people who are related, and I find some of them are sick and some of them are healthy, I might have a much better chance of figuring out which genes are involved.

But where do I do this? Well, one place is a little island nation in the North Atlantic, Iceland. In many ways, Iceland is the perfect place to look for genes that cause diseases. It's got a tiny population, only about 280,000 people, and virtually all of them are descended from the original settlers—Vikings who came here over 1000 years ago.

KARI STEFANSSON (President, deCODE Genetics): If you drive around this country you will have great difficulty finding any evidence of the dynamic culture that was here for almost 1100 years. There are no great buildings.There are no monuments.

ROBERT KRULWICH: But one thing Iceland does have is a fantastic written history, including almost everybody's family tree. And now it's all in a giant database. Just punch in a social security number and there they are, all your ancestors, right back to the original Viking.

THORDUR KRISTJANSSON (deCODE Genetics): So what we have here is my ancestor tree. I'm here at the bottom. This is my father and mother, my grandparents,great grandparents, and so on. We can find an individual that was one of the original settlers of Iceland. Here we have Ketill Bjarnarson, called Ketill Flatnefur, meaning he had a flat nose, so he may have broken it in a fight or something. And we estimate that he was born around the year 805.

ROBERT KRULWICH: Kari Stefansson is a Harvard-trained scientist who saw the potential gold mine that might be hidden in Iceland's genetic history. He set up a company called deCODE Genetics to combine age-old family trees with state-of-the-art DNA analysis and computer technology, and systematically hunt down the genes that cause disease.

KARI STEFANSON: Our idea was to try to bring together as much data on health care as possible, as much data on genetics as possible, and the genealogy, and simply use the informatics tools to help us to discover new knowledge, discover new ways to diagnose, treat and prevent diseases.

ROBERT KRULWICH: One of deCODE's first projects was to look for the genes that might cause osteoarthritis. Regnheidir Magnusdottir had the debilitating disease most of her life.

(Translation of) REGNHEIDIR MAGNUSDOTTIR (Arthritis patient): The first symptoms appeared when I was 12. And by the age of 14, my knees hurt very badly. No one really paid any attention. That's just the way it was. But by the age of 39, I'd had enough, so I went to a doctor.

ROBERT KRULWICH: Mrs. Magnusdottir was never alone in her suffering. She's one of 17 children. Eleven of them were so stricken with arthritis, they had to have their hips replaced. This was exactly the kind of family that deCode was looking for.

They got Mrs. Magnusdottir and other members of her family to donate blood samples for DNA analysis. And to find more of her relatives, people she'd never met, deCode just entered her social security number into their giant data base, and there they were.

But which of these people have arthritis? To find out, Stefansson asked the government of Iceland to give his company exclusive access to the entire country's medical records. And in exchange, deCode would pay a million dollars a year plus a share of any profits. That way, deCODE could link everything in their computers—DNA, health records and family trees.

KARI STEFANSSON: This idea was probably more debated than any other issue in the history of the Republic. On the eve of the Parliamentary vote on the bill there was an opinion poll taken which showed that 75 percent of those that took a stand on the issue supported the passage of the bill; 25 percent were against it.

ROBERT KRULWICH: Among that 25percent against the plan were most of Iceland's doctors.

TOMAS ZOEGA (Icelandic Medical Association): I felt there was something fundamentally wrong in all of this, you know? They do know everything about you, not only about your medical history, about your medical past, but they now do have your gene, the DNA. They know about your future, something about your children, about your relatives.

BJORN GUNDMARSSON (Havmnar Health Center): We find ourselves paralyzed because there is really nothing we can do, because the one who takes the responsibility, is the management of the health center. If they give away this information from the medical records they get money. And everybody needs money. Healthcare really needs money.

ROBERT KRULWICH: So what's really the problem here? Well let's take a hypothetical example. I'm going to make all this up. Let's pretend these are medical records of an average person. And we'll suppose that right here I see an HIV test, and then over here is medication for anxiety after what appears to be a messy divorce, and over here a parent who died of Alzheimer's.

Now, this is all stuff that could happen to anybody, but do you want it all in some central computer bank? And do you want it linked in the same computer to all your relatives and to your own personal DNA file? And should anybody have the right to go on a fishing expedition through your medical history and your DNA?

Well, it may be frightening, but it also might work. deCODE claims it has discovered several genes that may contribute to osteoarthritis. So this approach, combining family trees, medical records and DNA could lead to better drugs, or to cures for a whole range of diseases.

KARI STEFANSSON: To have all of the data in one place so you can use the modern informatics equipment to juxtapose the bits and pieces of data and look for the best fit, is an absolutely fascinating possibility.

ROBERT KRULWICH: Stefansson says no one's forced to do this, and there are elaborate privacy protections in place: no names are used and social security numbers are encoded. He also argues that the DNA part of the database is voluntary.

KARI STEFANSSON: The healthcare database only contains healthcare information. We can cross-reference it with DNA information but only from those individuals who have been willing to give us blood, allowing us to isolate DNA, genotype it and cross-reference it with the database. Only from those who have deliberately taken that risk. So it's not imposed on anyone, and no one who is scared of it, no one who is really afraid of it, should come and give us blood.

ROBERT KRULWICH: DNA databases are popping up all over the world, including the U.S. They all have rules for protecting privacy, but they still make ethicists nervous.

GEORGE ANNAS (Boston University): I like to use the analogy of the DNA molecule to a future diary—there's a lot of information in a DNA molecule. The reason I call it a diary, a future diary, is because I think it's that private. I don't think anybody should be able to open up your future diary except you.

ROBERT KRULWICH: One rather bleak vision of where all this could lead is presented in the Hollywood film "Gattaca." This is a world where everybody's DNA, everybody's future diary, is an open book. Everyone who can afford it has their children made to spec. But what happens to the poor slob who was conceived the old-fashioned way?

GATTACA VOICEOVER: "I'll never understand what possessed my mother to put her faith in God's hands rather than those of her local geneticist. Ten fingers, ten toes, that's all that used to matter. Not now. Now, only seconds old, the exact time and cause of my death was already known."

GATTACA NURSE: "Neurological condition, 60 percent probability; Attention Deficit Disorder, 89 percent probability; heart disorder, 99 percent probability; life expectancy, 30.2 years."

ROBERT KRULWICH: Thirty point two years. The nurse seems to know precisely what's going to happen to this baby. Which is ridiculous, right? Never happen. Or is it possible that one day we will be able to look with disturbing clarity into our future? Ten, twenty, even seventy years ahead?

GEORGE ANNAS: That is one possible future—where this becomes so routine that at birth, everybody gets a profile. It goes right to their medical record. One copy goes to the FBI so we have an identification system for all possible crimes in the United States. One copy goes...where? To the grade school? To the high school? To the college? To the employer? To the military? Like, a horrific future. Although I have to say there are many in the biotech industry and the medical profession who think that's a terrific future.

ROBERT KRULWICH: In fact, a lot of the technology already exists, now, today.

These guys in the funny suits are making gene chips. The little needles are dropping tiny, nearly invisible bits of DNA onto glass slides. And where did the DNA come from? From babies. Thousands of them.

Each chip can support eighty thousand different DNA tests.

MARK SCHENA (Stanford University): So a single chip, in principle, will allow you to test, say, 1000 babies for 80 different human diseases. So within a few minutes you can have a readout for thousands or even tens of thousands of babies in a single experiment.

ROBERT KRULWICH: Already babies are routinely tested for a handful of diseases. But with gene chips, everybody could be tested for hundreds of conditions.

MARK SCHENA: Knowing is great. Knowing early is even better. And that's really what the technology allows us to do.

ROBERT KRULWICH: Well, taking a test and knowing is great for the baby or anybody really, as long as there's something you can do about it. But think about this, because sometimes there may be a test but it might take 20 years or 50 years...50 years to find a cure. So you could take the test and you could learn that there is a disease coming your way but you can't do a thing about it. Do you still want to know?

Or you could take the test, but the test won't say that you're going to get the disease, it will simply say that you may get a disease. And as you know there's a big difference between" you will" and "you may."

Lissa Kapust and Lori Seigel are sisters who shared the wrenching experience of cancer in the family. Way back there were three sisters. And then in 1979 the youngest of the three, Melanie, was diagnosed with ovarian cancer.

LISSA KAPUST (Sister of ovarian cancer patient): When my sister was diagnosed, my response was disbelief. She was 30 years old. And I'd never known anybody of that age to have ovarian cancer.

ROBERT KRULWICH: Melanie fought her cancer for four years, but died in 1983. It seemed an isolated piece of bad luck. But then, just about a year later Lissa discovered she had breast cancer. She was only 34. But the cancer hadn't spread, so the long-term outlook seemed optimistic.

LISSA KAPUST: I actually had a radiation therapist who was tops in the field, wrote many books on breast cancer and was very optimistic. And what I remember him saying is that he and I would grow old together.

ROBERT KRULWICH: And Lissa was fine for 12 years. Then she found another lump in the same breast.

LISSA KAPUST: It was the worst fear come true. The first time I could hold on to hope. The second time, nobody was talking with me about living to be old.

ROBERT KRULWICH: When Lissa discovered her second cancer in 1996, scientists were just beginning to work out the link between breast and ovarian cancers that run in families. Mary-Claire King was one of the scientists who discovered that changes or mutations in two specific genes make a woman's risk of breast and ovarian cancer much higher.

The genes are called BRCA 1 and 2.

MARY-CLAIRE KING (University of Washington): BRCA 1 and BRCA 2 are perfectly healthy, normal genes that all of us have, but in a few families mutations in these genes are inherited.

ROBERT KRULWICH: So in a normal gene—see we're going to spell it out for you here letter by letter—this is the normal sequence ending G T A G C A G T. Now we're going to make a copy; now we're going to lose two of the letters, just two and then...see? Watch them shift over. Do you see that? This new configuration is a mutation which can often cause breast cancer.

MARY-CLAIRE KING: In the United States and Western Europe and Canada, the risk of developing breast cancer for women in the population as a whole is about 10 percent over the course of her lifetime, with, of course, most of that risk occurring later in her life. For a woman with a mutation in BRCA 1 or BRCA 2, the lifetime risk of breast cancer is about 80 percent. It's very high.

ROBERT KRULWICH: Right around the time of Lissa's second bout of breast cancer, a test for BRCA mutations became available. Lissa and her sister Lori decided to be tested.

LORI SIEGEL (Sister of ovarian cancer patient): I do remember the day that I went to find out the results. Panic. Terror. I mean, what was I going to find out? Talking about, you know, the blood surging through your temples. I mean I just remember sheer terror.

ROBERT KRULWICH: Turns out Lori was fine. But Lissa discovered that she does carry a BRCA mutation. It is not easy waking up every morning wondering if today is the day you may get sick.

DOCTOR: Any questions about the results from the biopsy from April?

LISSA KAPUST: No questions about the results. Again it feels like often my life is dodging bullets.

ROBERT KRULWICH: With the second cancer, Lissa had her right breast completely removed and then another operation to take out her ovaries.

NURSE: Okay, just keep a tight fist until I'm in.

ROBERT KRULWICH: She also has a high risk of cancer in her left breast. BRCA mutations are relatively rare and only cause maybe five or ten percent of all breast cancer. But knowing that there's a BRCA mutation in the family affects everybody.

ERIC KAPUST: The gene doesn't go away. The time passed since the last cancer doesn't buy you the safety. And the consequences run through the family. I suppose that for my daughter, who yet has not shown any significant impact of this, the knowledge that there's a genetic component that she can't deny will, I'm sure, color her life in serious ways.

ROBERT KRULWICH: Lissa's son, Justin, is 21. Her daughter, Alanna, is 18. There is a fifty-fifty chance that each of them has inherited the BRCA mutation from Lissa. The only way to know would be to take a test. And when should they do that? When is the right time?

ALANNA KAPUST (Daughter of breast cancer patient): I actually never really thought about it until biology this year, when my teacher posed a hypothetical, supposedly, question to people, saying, "What would you do? Can you imagine what you would do, if you were faced with the situation where you knew that you might have this disease that would be deadly. Or it would cause you to be sick and you could do a test that you could find out whether or not you had it?" And I was sitting there in class saying, "Maybe it's not so hypothetical."

ROBERT KRULWICH: And then, in her senior year of high school, Alanna felt a lump in her own breast.

ALANNA KAPUST: I did have the whole, "Oh it can't be happening to me. Not yet," kind of thing. I mean, I have the reservation in the back of my mind that eventually it may very well happen to me and if it does, then I'll fight it then. I'll deal with it then. But I don't expect...or I definitely didn't expect for this to be happening to me when I was 17 years old.

ROBERT KRULWICH: Alanna's lump was not cancer. And for now she doesn't want the test. Because if she knew that she had the bad gene, she'd only have two options: the choice of removing her breasts and ovaries to try to reduce her risk or just to be closely monitored and wait.

LISSA KAPUST: She's followed every year. Seems a little young to, you know, have her...to have to face that. On the other hand, it also feels like the belt and suspenders technique, we just have to do everything we can do.

ROBERT KRULWICH: In the next 20 years, this family's predicament will become more and more common as more and more genes are linked to more and more diseases and more tests become available. But we will all have to ask, "Do we want to know?" And when we know, can we live with an answer that says maybe, but maybe not?

LISSA KAPUST: Driving home from work today, I was tuned in to public radio and there was a professor of astronomy talking about a brand new telescope to look into the galaxies. And they're calling it the equivalent of the Human Genome Project. And I was thinking, "Hmm, not quite the equivalent of the Human Genome Project." Because it's without some of the ethical, moral angst—real people issues where it's a bit of a roller coaster ride between, you know, "This is going to hold answers, and hope, and treatments, and interventions, and cure." Versus, "It's not clear what this all means."

ROBERT KRULWICH: And if things aren't clear now, what about the future, when we may not only cure disease, but do so much more?

GATTACA GENETIC COUNSELOR: "Your extracted eggs, Marie, have been fertilized with Antonio's sperm. You have specified hazel eyes, dark hair and fair skin. All that remains is to select the most compatible candidate. I've taken the liberty of eradicating any potentially prejudicial conditions: premature baldness, myopia, alcoholism, obesity, et cetera."

GATTACA MOM: "We didn't want...I mean...diseases...yes, but..."

GATTACA DAD: "Right. And we were just wondering if it was good to leave a few things to chance."

GATTACA GENETIC COUNSELOR: "You want to give your child the best possible start. And keep in mind this child is still you, simply the best of you. You could conceive naturally a thousand times and never get such a result."

FRANCIS COLLINS: Gattaca really raised some interesting points. The technology that's being described there is, in fact, right in front of us or almost in front of us.

ROBERT KRULWICH: That seems to me almost extremely likely to happen, because what parent wouldn't want to introduce a child that wouldn't have...at least be where all the other kids could be?

FRANCIS COLLINS: That's why the scenario is chilling. It portrayed a society where genetic determinism had basically run wild. I think society in general has smiled upon the use of genetics for preventing terrible diseases. But when you begin to blur that boundary of making your kids genetically different in a way that enhances their performance in some way, that starts to make most of us uneasy.

ROBERT KRULWICH: What if we lived in the world of Star Trek Voyager? Talk about uneasy. Lieutenant Torres is 50 percent human and 50 percent Klingon. She's also 100 percent pregnant. Like any caring parent, she doesn't want her unborn child to be teased for having a forehead that looks like...well, like a tire-tread. But, here's the twist. She can do something about it.

Mmm, she threw in some blond hair, too.

And is this the limit? Or could we go even further? If you can eventually isolate all these things, can you then build a creature that has never existed before? For example, I would like the eyesight of a hawk, and I'd like the hearing of a dog. Otherwise, I'm quite content to be exactly as I am. So, could I pluck the eyesight and the hearing and patch it in?

ERIC LANDER: Well, we don't know. We really don't know how that engineering occurs and how we can improve on it. It would be very much like getting a whole pile of parts to a Boeing 777 and a whole pile of parts to an Airbus, and saying, "Well, I'm going to mix and match some of these so it will have some of the properties. I make it a little fatter, but I also want to make it a little shorter." And by the time you were done you'd think you'd made lots of clever improvements, but the thing wouldn't get off the ground.

It's a very complex machine, and going in with a monkey wrench to change a piece...the odds are most changes we would make today, almost all changes we'd make today, would break the machine.

ROBERT KRULWICH: We may not be able to genetically modify humans or Klingons yet, but we do do it to plants and animals every day. Look at this stuff: tobacco plants with a gene from a firefly. And they used that same insect gene to create glowing mice. So, it's theoretically possible that we could create humans with other advantages that borrowed from other creatures.

ERIC LANDER: That's right. But the humility of science right now, is to appreciate how little we know about how you could even begin to go about that. What is the difference between the twentieth century and twenty-first century biology is it's now our job, in this century, to figure out how the parts fit together.

ROBERT KRULWICH: And just as the twentieth century was winding down, the race to finish the genome was reaching full throttle. The competitive juices were flowing.

J. CRAIG VENTER: I am competitive, but when the social order doesn't allow you to make progress, and it doesn't for most people, I say "To hell with the social order. Well, I'll find a new way to do it."

TONY WHITE: It changed the paradigm on people, and people don't like that. It was very offensive to these people: "How dare they," you know, "rain on our parade? This is our turf."

ERIC LANDER: This was a challenge to the whole idea of public generation of data. That's what offended people, was that we really felt deeply that these were data that had to be available for everybody. And there was an attempt to claim the public imagination for the proposition that these data were better done in some private fashion and owned.

TONY WHITE: You know, you want to say, "Well, wait a minute. If you could do it in two years, why weren't you doing it in two years? Why did we have to come along to turn a 15 year project into a two year project."

ERIC LANDER: I must say the human genome project had a tremendous amount of internal competition, even amongst the academic groups. There's competition amongst academic scientists to be sure, and more than anything, there's competition against disease. There's a strong sense that what we're trying to find out is the most important information that you could possibly get.

TONY WHITE: I don't know. I mean, I hope that this will all go away.

ROBERT KRULWICH: In June of 2000, it kind of did go away. The contentious race to finish the genome came to an end. And the winner was...?

Well, you probably heard. They decided to call it a tie.

FRANCIS COLLIINS: I think both Craig and I were really tired of the way in which the representations had played out and wanted to see that sort of put behind us. It was probably not good for Celera as a business to have this image of being sort of always in contention with the public project. It certainly wasn't good for the public project to be seen as battling with a private sector enterprise.

ROBERT KRULWICH: President Clinton himself got the public guys and the Celera guys to play nice, shake hands, and share the credit for sequencing the genome.

TAPE OF PRESIDENT WILLIAM JEFFERSON CLINTON: "Nearly two centuries ago, in this room, on this floor, Thomas Jefferson and a trusted aide spread out a magnificent map. The aide was Meriwether Lewis, and the map was the product of his courageous expedition across the American frontier all the way to the Pacific. Today the world is joining us here in the East Room to behold a map of even greater significance. We are here to celebrate the completion of the first survey of the entire human genome. Without a doubt this is the most important, most wondrous map ever produced by humankind."

ROBERT KRULWICH: And what does this map the President is talking about...what does it look like? When we look across the landscape of our DNA for the 30,000 genes that make up a human being, what do we see?

ERIC LANDER: The genome is very lumpy.

ROBERT KRULWICH: Very lumpy?

ERIC LANDER: Very lumpy, very uneven. You might think, if we have 30,000 genes, they're kind of distributed uniformly across the chromosomes. Not so. They're distributed like people are distributed in America: they're all bunched up in some places, and then you have vast plains that don't have a lot of people in them. It's like that with the genes. There are really gene-dense regions that might have 15 times the density of genes, sort of New York City over here. And there are other regions that might go for two million letters and there's not a gene to be found in there. The remarkable thing about our genome is how little gene there is in it. We have three billion letters of DNA, but only one, one point five percent of it is gene.

ROBERT KRULWICH: One and a half percent?

ERIC LANDER: The rest of it, 99 percent of it, is stuff.

ROBERT KRULWICH: Stuff. This is a technical term?

ERIC LANDER: A technical term. More than half of your total DNA, is not really yours. It consists of selfish DNA elements that somehow got into our genomes about a billion and a half years ago, and have been hopping around, making copies of themselves. To those selfish DNA elements...we're merely a host for them. They view the human being just as a vehicle for transmitting themselves.

ROBERT KRULWICH: Wait a second, wait a second, wait a second. We have in each and every one of our cells that carry DNA, we have these little, they're not beings, they're just hitchhiking? Hitchhikers?

ERIC LANDER: Hitchhiking chunks of DNA.

ROBERT KRULWICH: And they've been in us for how long?

ERIC LANDER: About a billion and a half years or so.

ROBERT KRULWICH: And all they've done is far as you can say is stay there and multiply?

ERIC LANDER: Well, they move around.

ROBERT KRULWICH: And what is that? What do you call that? I mean, it's not an animal, it's not a vegetable, it's just...

ERIC LANDER: It's just a gene that knows how to look out for itself and nothing else.

ROBERT KRULWICH: And it's just riding around in us, through time?

ERIC LANDER: It rides around in us. The majority of our genome is this stuff, not us.

ROBERT KRULWICH: Wow. It is a little humbling to think that we, the paragon of animals, the architects of great civilizations, are used as taxicabs by a bunch of freeloading parasites who could care less about us. But that's the mystery of it all.

ERIC LANDER: You come away from reading the genome recognizing that we are so similar to every other living thing on this planet. And every innovation in us—we didn't really invent it. These were all things inherited from our ancestors.

This gives you a tremendous respect for life. It gives you respect for the complexity of life, the innovation of life, and the tremendous connectivity amongst all life on the planet.

ROBERT KRULWICH: We are, in a very real sense, ordinary creatures. Our parts are interchangeable with all the other animals and even the plants around us! And yet we know there is something about us that is truly extraordinary.

What it is, we don't know. But what it does is it lets us ask questions, and investigate and contemplate the messages buried in a molecule shaped like a twisted staircase. That's what we, and maybe we alone can do.

We can wonder.

Nerf® is a registered trademark of Hasbro, Inc.

Cracking the Code of Life

Correspondent

Robert Krulwich

Written and Produced by

Elizabeth Arledge and Julia Cort

Directed by

Elizabeth Arledge

Animation by

Anatomical Travelogue, Inc.

Edited by

Caren Myers
Doug Quade

Associate Producer

Whitney Johnson

Scientific Advisor

Dr. David Page
Whitehead Institute/MIT

Principal Photography

Ben McCoy
Erich Roland

Music

Ray Loring

Sound Recordists

Steven L. Lederer
Thomas P. Williams

Additional Photography

Brian Dowley
Jim Hilling

Additional Editing

Dave Skowronski

Assistant Editor

Dan Van Roekel

Online Editor

Dave Allen

Audio Mix

Brian S. Cunneff

Colorist

Greg D. Conners

Associate Producer for NOVA

Jennifer Lorenz

Production Assistants for NOVA

Jennifer Callahan
Christian Rodriguez

Advisory Board

Dr. David Baltimore
Dr. Paul Berg
Dr. Lydia Villa-Komaroff
Dr. Georgia Dunston
Dr. Philip Reilly
Dr. David Blumenthal
Dr. Ronald Crystal
Dr. French Anderson

Special Thanks

National Institute of Human Genome Research
Whitehead/MIT Center for Genome Research
Celera Genomics
Children's Hospital, Boston
Washington University, St. Louis
Beth Israel Deaconess Medical Center, Boston
University of Washington
DeCODE Genetics
Icelandic Medical Association
National Tay Sachs and Allied Diseases Association
arrayit.com
ABC News
Meredith Kirk
Daniel J. Richter

For Clear Blue Sky Productions:

Executive-in-Charge

Jody Patton

Presented by

Paul G. Allen

Executive Producer

Eric Robison

Director, Documentary Productions

Bonnie Benjamin-Phariss

Coordinating Producer

Pamela Rosenstein

Director, Publicity and Marketing

Jason J. Hunke

Production Coordinator

Pilar Binyon

For NOVA

NOVA Series Graphics

National Ministry of Design

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Mason Daring
Martin Brody
Michael Whalen

Post Production Online Editors

Spencer Gentry
Mark Steele

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The Caption Center

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Queene Coyne
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Publicity

Jonathan Renes
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Senior Researcher

Ethan Herberman

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Legal Counsel

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Business Manager

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Lila White Gardella
Patrick Carey

Assistant Editor, Post Production

Regina O'Toole

Associate Producer, Post Production

Judy Bourg

Post Production Editor

Rebecca Nieto

Production Managers, Post Production

Lisa D'Angelo
Laura Azevedo

Senior Science Editor

Evan Hadingham

Senior Series Producer

Melanie Wallace

Managing Director

Alan Ritsko

Executive Producer for NOVA

Paula S. Apsell

A Production of NOVA/Clear Blue Sky Productions by Elizabeth Arledge for WGBH/Boston.

© 2001 WGBH Educational Foundation and Clear Blue Sky Productions

All Rights Reserved.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Links

National Human Genome Research Institute
http://www.genome.gov/
The National Human Genome Research Institute is the hub of the Human Genome Project. Visit this site for accurate information about all aspects of the Human Genome Project and a wealth of carefully compiled resources, including a glossary of genetic terms and an extensive guide to other genome-related websites.

Glossary of Genetic Terms
http://www.genome.gov/glossary/index.cfm
Have you ever wished your dictionary could speak to you? This genome glossary offers a definition for almost any genetic term you can think of, provides a clear illustration of the term, invites you to explore related terms, and—ta da!—you can hear each term explained aloud by a specialist in the field of genetics.

Ensembl Browse a Genome
http://useast.ensembl.org/index.html
There are thousands of websites related to genomics. This jump site regularly updates its annotated list of links and promises to help you sort through the genome Web jungle to find the best online resources.

GenomeWeb
http://www.genomeweb.com/
GenomeWeb is another useful jump site, which arranges its lists of links by category. If you are looking for information on a particular topic, say, a list of the top biogenetics research companies in the world, this site may be just what you need.

Dolan DNA Learning Center
http://www.dnalc.org/
This website takes the concept of interactivity to the nth degree. Roll up your sleeves and visit the Cold Spring Harbor Laboratory's Dolan DNA Learning Center, where you'll find dozens of sophisticated genetic activities and games.

GeneCards
http://www.genecards.org/
GeneCards, provided by the Weizmann Institute of Science, is a database of human genes and their relationship to diseases. It offers concise information about the functions of all the human genes we know about, and allows you to scroll through the code for each gene listed. This site is geared primarily towards scientists and researchers.

National Center for Biotechnology Information
http://www.ncbi.nlm.nih.gov/genome/guide/human/
This hub page for Human Genome Resources offers biomedical researchers around the world a one-stop resource for data that may be used in research efforts.

National Tay-Sachs and Allied Diseases Association
http://www.ntsad.org/
Visit this website for more information about Tay-Sachs, a devastating genetic disorder.

Cameron and Hayden Lord Foundation
http://www.lordfoundation.org/
Cameron and Hayden Lord's stories are featured in "Cracking the Code of Life." Their parents began a foundation in their honor to provide resources for parents with terminally ill children, particularly those who suffer from Tay-Sachs. Peruse this thoughtful site for tips on caring for terminally ill children and to learn more about the disorder.

Cystic Fibrosis Foundation
http://www.cff.org/
Find a clinical trial, volunteer your time, and learn about news and events on this comprehensive website about this debilitating genetic disorder.

American Cancer Society
http://www.cancer.org/
Learn about various types of cancer, find support and treatment, explore the latest research, and more on this extensive website.

Books

Cracking the Genome: Inside the Race to Unlock Human DNA
by Kevin Davies. The Free Press, 2001.

The Lives to Come: The Genetic Revolution and Human Possibilities
by Philip Kitcher. Simon & Schuster, 1996.

Genome: The Autobiography of a Species in 23 Chapters
by Matt Ridley. Perennial, 2000.

Special Thanks

Geoff Spencer

National Human Genome Research Institute

Whitehead Institute for Genome Research/MIT:

Dr. Bruce Birren

Dr. Joel Hirschhorn

Seema Kumar