Program Description

Cracking the genetic code NOVA. NOVA: Cracking the Code of Life. Cracking the Code of Life. PDBio 220 - Origins/Insertions/Actions. THIS SET IS OFTEN IN FOLDERS WITH. SCIENCE- Cracking your Genetic Code. Chapter 2.2 Assessment. Nutrient Cycle Color Coded Word. Jun 23, 2015  CRACKING YOUR GENETIC CODE PBS Airdate: March 28th, 2012 Total time: approx. Major funding for NOVA is provided by: The David H. Koch Fund For.

(Program not available for streaming.) This two-hour special, hosted by ABC 'Nightline' correspondent Robert Krulwich, chronicles the fiercely competitive race to capture one of the biggest scientific prizes ever: the complete letter-by-letter sequence of genetic information that defines human life—the human genome. NOVA tells the story of the genome triumph and its profound implications for medicine and human health.

Transcript

Cracking the Code of Life

PBS Airdate: April 17, 2001

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

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

ROBERT KRULWICH: This is the story of one of the greatestscientific adventures ever, and at the heart of it is a small, very powerfulmolecule, DNA.

For the past ten years, scientists all over the world have beenpainstakingly trying to read the tiny instructions buried inside our DNA. Andnow, finally, the 'Human Genome' has been decoded.

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

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

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

ERIC LANDER: How different are you from a banana?

ROBERT KRULWICH: I feel...and I feel I can say this with someauthority...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 themachinery for controlling the cell cycle, the cell surface, for makingnutrients, all that's the same.'

ROBERT KRULWICH: So what does any of this information have todo with you or me? Perhaps more than we could possibly imagine. Which one of uswill get cancer or arthritis or Alzheimer's? Will there be cures? Will parentsin the future be able to determine their children's geneticdestinies?

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

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

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

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

Major funding for NOVA is provided by the Park Foundation, dedicated toeducation and quality television.

This program is funded in part by the Northwestern Mutual Foundation. Somepeople already know Northwestern Mutual can help plan for your children'seducation. Are you there yet? Northwestern Mutual Financial Network.

Scientific achievement is fueled by the simple desire to make things clear.Sprint PCS is proud to support NOVA.

Major funding for this program is provided by the National ScienceFoundation, America's investment in the future. And by the Corporation forPublic Broadcasting, and by contributions to your PBS station from viewers likeyou. Thank You.

ROBERT KRULWICH: To begin, let's go back four and some billionyears 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 goneon uninterrupted ever since. It wrote a message. It was a chemical messagethat it passed to its children, which then passed it on to its children, and toits 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 throughall living things.

It's more elaborate now, of course, but that message, very simply, is thesecret of life. And here is that message contained in this stunning littleconstellation of chemicals we call DNA. You've seen it in this form, theclassic double helix, but since we're going to be spending a lot of timetalking 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 mysticalhigh-falutin' sort of molecule—all this information, your future, yourheredity. It's actually goop. So this here's DNA.

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

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

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

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

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

But how do you read what's inside a molecule? Well, if it's DNA, if youturn it so you can look at it from just the right angle, you will see in themiddle 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, calledbase pairs, either C and G, or T and A for short. This is, step by step, acode, three billion steps long—the formula for a human being.

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

ERIC LANDER: ...double helix...

ROBERT KRULWICH: ...double helix. First of all, I'mwondering...this is my version of a DNA molecule. Is this, by the way, what itlooks 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 cellin your body, if you look deep enough, you will find this chainhere?

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

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

ERIC LANDER: Oh golly...

ROBERT KRULWICH: Look at this. He's asking forhelp.

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

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

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

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

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

ROBERT KRULWICH: But the main thing about this is theladder, the steps of this ladder. If I knew it was A and T and C and C and Gand 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 thegrammar, yeah...if I could read each of the individual ladders, I might findthe picture of what?

ERIC LANDER: Well, of your children. This is what you pass to yourchildren. You know people have known for 2000 years that your kids look a lotlike you. Well it's because you must pass them something, some instructionsthat give them the eyes they have and the hair color they have and the noseshape 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 thismolecule, we're going to start with one atom deep inside, and we pull back andyou see it form its As and Ts and Cs and Gs and the classic double spiral. Andthen it starts the mysterious process that creates a healthy new baby. And theinteresting thing is that every human baby, every baby born, is 99.9 percentidentical in its genetic code to every other baby.

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

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

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

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

ROBERT KRULWICH: ...frustratingly prone tomistakes...

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 wayit used to be done.

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

ROBERT KRULWICH: And we haven't mentioned the hardest part.This here, magnified 50,000 times is an actual clump of DNA, chromosome 17. Nowif you look inside you will find, of course, hundreds of millions of As, andCs, and Ts and Gs, but it turns out that only about one percent of them areactive and important. These are the genes that scientists are searching for. Sosomewhere in this dense chemical forest are genes involved in deafness,Alzheimer's, cancer, cataracts. But where? This is such a maze scientists needa 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 tenyears the entire process has been computerized. That cost hundreds of millionsof dollars. But now, instead of decoding a few hundred letters by hand in aday, together these machines can do a thousand every second and that has madeall the difference.

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

ROBERT KRULWICH: Getting the letters out is...has beendescribed as finding the blueprint of a human being, finding a manual for ahuman being, finding the code of the human being. What's yourmetaphor?

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. Blueprintsand all these fancy... It's just a parts list. It's a parts list with a lot ofparts. If you take an airplane, a Boeing 777, I think it has like 100,000parts. If I gave you a parts list for the Boeing 777 in one sense you'd know alot. You'd know 100,000 components that have got to be there, screws and wiresand rudders and things like that. On the other hand, I bet you wouldn't knowhow to put it together. And I bet you wouldn't know why it flies. Well we're inthe same boat. We now have a parts list. That's what the human genome projectis about is getting the parts list. If you want to understand the plane youhave 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 tounderstand all those parts, to decode every letter of the genome, is becausesometimes, out of three billion base pairs in our DNA, just one single lettercan 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 Ithink of the most about Hayden, which a lot of people got from him right fromthe beginning is that he was always, I thought, very funny. I mean he loved tosmile and laugh and he just used to guffaw. And this was later when he wasabout a year old, he just found the funniest things hilarious. And so he and Iwould just crack each other up.

ROBERT KRULWICH: Hayden seemed to be developing normally forthe first few months but Allison began to notice that some things were notquite right.

ALLISON LORD (Mother of son with Tay Sachs): I was very anxiousall the time with Hayden. I sensed that something was not the same. I would seemy 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 thingslike that, and Hayden didn't do that.

ROBERT KRULWICH: Doctors told them that Hayden was justdeveloping a bit slowly. But by the time he turned a year old, it was clearsomething serious was wrong. He never crawled, he never talked, he never atewith his fingers and he seemed to be going backwards, notprogressing.

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

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

DR. EDWIN KOLODNY (NYU, Department of Neurology): What happens isthe child appears normal at birth, and over the course of the first year beginsto miss developmental milestones. So at six months a child should be turningover—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 onthe DNA ladder, when just one letter goes wrong. Say this cluster of atoms isa 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 inthis protein which is supposed to dissolve the fat in the brain. Butnow the protein doesn't work. So fat builds up, swells the brain, andeventually strangles and crushes critical brain cells. And all of this is theresult of one bad letter in that baby' s DNA.

DR. EDWIN KOLODNY: In most cases it's a single base change. As we say, aletter 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 progressivedisease. In the year since his diagnosis, Hayden has gone blind. He can't eatsolid food. It's harder and harder for him to swallow. He can't move on his ownat 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 twinbrother. When Hayden was diagnosed, that brother, Charlie, went to New York tobe 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 methat Hayden had Tay Sachs. He called me on the phone and he told meimmediately what it was. I went up into the computer and looked it up and thenjust couldn't believe what I read.

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

BLYTH LORD: On the NTSAD Website it talks about typically between sixand eight months is when the signs start coming, but one of the early signs isthat they startle easily. And Hayden had always had a really heavy startleresponse. 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 onthe Tay Sachs Website, Blyth went to get herself and Cameron tested.

CHARLIE LORD (Mother of daughter with Tay Sachs): It was anotherweek. It was exactly a week until we got the final results on Cameron's bloodwork. And then the Tuesday before Thanksgiving we went into our pediatrician'soffice and he had the results, and we found out that night that Blyth was acarrier 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 itusually occurs in specific groups, like Ashkenazi Jews. And even then, the babymust inherit the bad gene from both parents. So even though there is a TaySachs test, the Lords had no reason to think they would be at risk. And yetincredibly, all four of them, Tim and Charlie and both their wives—all fourwere carriers. That was an unbelievably bad roll of the geneticdice.

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

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

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

TIM LORD: I would like to see a really aggressive push to develop a testfor hundreds of genetic diseases so that parents could be informed before theystarted to have children as to the dangers that face them. And I think it'swithin our grasp. Now that they've mapped the human genome, I mean, theinformation 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 awhole host of them and not have them affect a child, I think it's somethingthat we have to focus on.

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

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

And that's why, when Congress created the Human Genome Project in 1990, thechallenge was to get a complete list of our As, Ts, Cs and Gs as quickly aspossible, 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 thetime that seemed reasonable.

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

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

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

J. CRAIG VENTER: It took ten years to get the protein and it took awhole 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'regazing out the window?

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

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

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

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

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 Ccoming 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 haveto be put together again in the right order. Venter's dream was to havehundreds of new machines at his fingertips so he quit his government job andformed a company he called Celera Genomics. Celera from the Latin wordcelerity, meaning speed. And this is what he built.

Oh, my Lord. And you know why that's interesting? There's almost nobodyhere.

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

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

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

When you're young and you see a lot of people die and they all could beyou, do you then feel that you sort of owe them cures? Cures that they'll neverget? Or am I over-romanticizing?

J. CRAIG VENTER: Well, the motivations become complex. That's certainlya part of it. Also I think surviving the year there was...it sort of putsthings in perspective, I think. If you're not in that situation, you can nevertruly 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 giftfor all these years since I got back in 1968, and I wanted to make sure I didsomething with it.

ROBERT KRULWICH: In the spring of 1998, Venter announced thathe and his company were going to sequence all three billion letters of thehuman genome in two years. Remember, the government said it would take15.

J. CRAIG VENTER: There was a lot of arrogance that went with thatprogram. 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 theyplanned to retire doing this program. That's not what we think is the right wayto do science, especially science that affects so many people's lives.

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

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

HUMAN GENOME PROJECT STAFF MEMBER: There are some limitations. We don'tthink we can get this thing to go any faster at the moment without throwing alot more robotics at it. The arm physically takes twenty seconds to...

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

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

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

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

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

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

ROBERT KRULWICH: At MIT a different crate is arriving almostdaily.

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

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

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

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

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

ROBERT KRULWICH: The MIT crew is particularly excited abouttheir brand new three-hundred-thousand-dollar state-of-the-art DNApurifying machine.

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

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

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

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

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

ROBERT KRULWICH: So he calls the customer service line. And ofcourse he's put on hold. So he waits. And he waits. And he waits. Anyway, itturns out that the three-hundred-thousand-dollar machine does have one tinylittle 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 reallyworking. And so it's incredibly complicated.

MIT STAFF RESEARCHER FIVE: So we have a test transformation where wetransform 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 havethree-eighty-four-well plates.

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

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

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

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

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

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

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

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

TONY WHITE: That's publicly available data. I'm a taxpayer. Celera's ataxpayer. 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? Isthat the idea? It isn't about us getting the data. It's about this academicjealousy. It's about the fact that our data, in combination with theirs, givesus 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'tthey?

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 everybodycan go use it.

ROBERT KRULWICH: Since Celera was sequencing the genome withprivate money, some critics wondered, 'Why should the government put so muchcash into the exact same research?'

ERIC LANDER: In the United States, we invested in a national highwaysystem in the 1950s. We got tremendous return for building roads for free andletting 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 upand down those chromosomes for anything they want to. They can makediscoveries. They can learn about medicine. They can learn about history.Whatever they want. It is worth the public investment to make those roadsavailable.

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

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

ROBERT KRULWICH: Whoa, whoa. An anonymous couple fromBuffalo?

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 sothey put an ad in Buffalo newspapers and they got random volunteers fromBuffalo. They got about 20 of them, and chose at random this sample and thatsample and that sample. So nobody knows who they are.

ROBERT KRULWICH: And what about Celera? Whose DNA are theymapping?

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

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

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

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

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

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

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

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

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

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

ROBERT KRULWICH: And if I were to bring secretly into anotherroom, a black man, an Asian man, and a white man, and show you only theirgenetic 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, veryclosely related. 'Cause any two humans being 99.9 percent identical means thatwe're much more closely related than any two chimpanzees in Africa.

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

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

ROBERT KRULWICH: Because we're such a youngspecies?

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

ROBERT KRULWICH: So people are incredibly similar to eachother. But not only that. It turns out we also share many geneswith...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 someauthority...very different from a banana.

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

ROBERT KRULWICH: I eat a banana, but I havenever...

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

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

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

ROBERT KRULWICH: Now, does that mean—I just want to make sureif I understand this right. Does that mean when you look through those thingsthat all the Cs and the As and the Ts and the Ts and the Gs...are you seeingthe exact same letter sequences in the exact same alignment? When you look atthe 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 almostidentical. There are some genes, like ubiquitin, that's 97percent identicalbetween humans and yeast, even after a billion years of evolution.

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

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

ROBERT KRULWICH: It seems incredible but all this informationabout 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 theHuman Genome Project progressed and hit high gear the pace of discoveryquickened. Once they got fully automated, it wasn't long before Lander andCollins and all the other public project teams had reason tocelebrate.

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

ROBERT KRULWICH: By November of 1999, they had reached a majormilestone. In a five-way awards ceremony, hooked up by satellite, themajor 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 atoast. A billion base pairs, all on the public Internet, available to anybodyin the world. It's an incredible achievement. It hasn't been completelypainless. And because I know everybody in this room is living and breathing andthinking every single moment in the day, about how to make all this happen, howwe can hit full scale I want to be sure you realize what a remarkable thing wepulled off. I hope you also know that this is history. Whatever else you do inyour lives, you're part of history. We're part of an amazing effort on the partof the world to produce this. And this isn't going to be like the moon, wherewe 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 tremendouslyproud of you. A toast to this remarkable group, to the work we've done, to thework ahead. Hear, hear.

ROBERT KRULWICH: Everybody here is hoping the Genome Projectwill help cure disease, and the sooner it's done, the better for all of us. Butthere's something more than idealism, more than even pride that's driving thisrace to finish the genome. And that is the knowledge that with every day thatpasses more and more pieces of our genome are being turned into privateproperty by way of the US Patent Office.

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

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

TODD DICKINSON (Former Director, US Patent Office): We regardgenes as a patentable subject matter as we regard almost any chemical. We haveissued patents on a number of compounds, a number of compositions that arefound in the human body. For example the gene that encodes for insulin has beenpatented. And that now is used to make almost all of the insulin that is madeso 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 humanbody, there would be an awful lot of inventions that would not be able to beprotected.

ROBERT KRULWICH: Generally, to patent an invention, you've gotto prove that it's new and useful. But a few years ago, critics said the patentoffice wasn't being tough enough. So applicants would say, 'Well, here's abrand 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 vagueabout use,' says Eric Lander.

ERIC LANDER: The sort of thing that people used to do then was theywould 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 tostuff in a box.' I mean, it's true. It takes up space.

ROBERT KRULWICH: Wouldn't the patent examiner say, 'That's notuseful.'

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'vereally invented a cure for a disease, some really important therapy. I doobject to giving a monopoly when somebody has simply described a couple hundredletters of a gene, has no idea what use you could have in medicine. Becausewhat's going to happen is you've given away that precious monopoly to somebodywho's done a little bit of work. And then the people who want to come along anddo a lot of work, to turn it into a therapy, well they've got to go pay theperson who already owns it. I think it's a bad deal for society.

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

This can cause problems for drug companies who are trying to work withgenes to cure disease. I'm a company trying to do work on this, this, and thisrung of the ladder because I think I can maybe develop a cure for cancer righthere, just for the sake of argument. But of course I have to worry thatsomebody owns this space.

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

ROBERT KRULWICH: Because one day the phone rings andsays '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 goingto charge you $100,000 a week.' Or 'You can work here and I'll charge you anickel but I want 50 percent of whatever you discover or any ofit.'

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

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

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

SHELDON KRIMSKY (Science Policy Analyst, TuftsUniversity): Every scientist who does research is now being looked uponas a generator of wealth, even if that person is not interested in it. If theysequence some DNA, that could be patentable material. So whether the scientistlikes it or not, he or she becomes an entrepreneur just by virtue of doingscience.

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

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

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

J. CRAIG VENTER: I think I bristle at it because it's used as anattack, 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 milliondollars 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 isCelera's Master Control. Twenty-four hours a day, technicians monitor all thecompany's major operations, including the hundreds of sequencers that areconstantly 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 bigbrowser, a user-friendly interface between you and your genes.

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

ROBERT KRULWICH: So Celera's business plan is to gatherinformation from all kinds of creatures, put it together and sell theirfindings to drug companies or universities or whomever. But it's the sellingpart, selling scientific information, that makes some scientists veryuncomfortable.

SHELDON KRIMSKY: This is a big change in the ethos of the scientificcommunity, which is supposedly...it was built upon the idea of communitarianvalues of the free and open exchange of information. The fundamental idea thatwhen 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? Theycould 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 withmaking money from the human genome.

TONY WHITE: I hope we have a legal monopoly on the information. I hopeour product is so good, and so valuable to people, that they feel that it'snecessary 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 bein, do you think, the landlord business, or this, 'You subscribe, and I'll giveyou 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 realbusiness. 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 taughtus, it's that finding cures is a whole lot harder than simply reading lettersof DNA.

Take, for example, the case of little Riley Demanche. At two months, Rileyappears to be a perfectly healthy baby boy. But he's not. When Riley was just13 days old, Kathy Demanche got the call that every parent dreads.

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

And I was in shock.

ROBERT KRULWICH: As Kathy and her husband would soonlearn, cystic fibrosis, CF for short, attacks several organs of the body, butespecially 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 tohave a normal and healthy, happy and long life. But at the present time, Idon't have any guarantees about that.

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

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

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

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

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

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

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

ROBERT KRULWICH: The original hope was that babies likeRiley could be cured by gene therapy, medicine that could provide a goodworking copy of a broken gene. But attempts at gene therapy have hardly everworked. They remain highly controversial. So if there's going to be aneffective treatment for Riley, instead of fixing his genes, we're going to takea 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 seeDNA. You don't see RNA. You see proteins and the result of protein action. Sothat'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 casewhere the genes create the proteins and the proteins create us?

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

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

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

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

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

FRANCIS COLLINS: They have needs and reasons to want to besnuggled up against each other in a particular way. And actually a particularamino 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 donot have the ability to precisely predict how that's going to work. Butobviously it does work.

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

Because it is now misshapen, and a key protein that is found in lungcells, 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 theprotein 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 healthyprotein 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 isgetting through.

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

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

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 cakecompared to most other things, because genetic information is linear. It goesin a simple line up and down the chromosome. Once you start talking about thethree-dimensional shapes into which protein chains can fold and how they canstick to each other in many different ways to do things, or the ways in whichcells can interact, like wiring up in your brain, you're not in aone-dimensional problem anymore. You're not in Kansas anymore.

ROBERT KRULWICH: And as scientists head into the worldof proteins, they're looking very closely at patients like TonyRamos.

Tony has cystic fibrosis, but it's not the typical case. CF almost alwaysdevelops 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 stepmotherthought, 'That's not right.' So I started going to doctors trying to figure itout 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'sfamily was told she might not survive beyond her twenty-first birthday. She isnow in her mid-forties, but her CF is worsening. Two or three times a year, shedoes have to be admitted to the hospital to clean out her lungs.

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

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

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

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

ROBERT KRULWICH: Could it be that Tony has some othergenetic mutations, good mutations that are producing good proteins that kepther healthy for 15 years? That are keeping her alive rightnow?

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

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

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

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

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

ERIC LANDER: The proteome.

ROBERT KRULWICH: The proteome. What's that?

ERIC LANDER: Well, the genome is the collection of all your genesand DNA. The proteome is the collection of all your proteins. See, what'shappening is we're realizing that if we wanted to understand life, wehad to start systematically at the bottom and get all the building blocks. Thefirst 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 allthe work of your cell. Then we've got to understand what each of those proteinsdoes, what its shape is, how they interact with each other, and how they makekind of circuits and connections with each other. So in some sense, this isjust the beginning of a very comprehensive, systematic program to understandall the components and how they all connect with each other.

ROBERT KRULWICH: All the components and how theyconnect? But how many components are there? How many genes and how manyproteins do we have?

ERIC LANDER: The real shock about the genome sequence was that wehave so many fewer genes than we've been teaching our students. The officialtextbook answer is, 'The human has 100,000 genes.' Everybody's known that sincethe early 1980s. The only problem is it's not true. Turns out we only have30,000 or so genes.

ROBERT KRULWICH: Thirty thousand genes? That's it? Noteverybody agrees with this number but that's about as many as a mouse! Even afruit fly has 14,000 genes.

ERIC LANDER: That's really bothersome to many people, that we only haveabout twice as many genes as a fruit fly, because we really like to think ofourselves 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 soit raises two questions. Are we really more complex?

ROBERT KRULWICH: You show me the fruit fly that cancompose 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, wehave lots of genes that are virtually identical in us and fruit flies. Buthappily, our genes seem to do more.

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

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

ROBERT KRULWICH: So, starting with the same rawingredients, 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 themelodies yet. We can...one of the exciting things about reading the genomesequence now is we're getting a glimpse at that complexity of the parts, andhow it's a symphony rather than a simple tune. But it's not that easy to justread the sheet music there and hear the symphony that's coming out ofit.

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

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

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

GENE MYERS (Vice President, Informatics Research, Celera): Thepace of things and the magnitude of things was really incredible. I mean, Iwould remember coming in and just having this really gripping feeling in mygut, 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 theHuman Genome out there in the world first, they're going to be famous. They'regoing 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, whenthat's going on, it's not unreasonable that people are going to reach for thatstar and try to get there before the other person.

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

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

GENE MYERS: The environment at Celera was really intense, and itreminded me of finals week at Cal Tech. And there's a tradition at Cal Techthat on the very first day of finals week, The Ride of the Valkyries isplayed at full blast. And so, I thought, 'Well, since every week feels likeit's finals week here, why don't I play The Ride, and see whathappens.'

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 eachother. And we go, 'You know, there's something not right about this.' So wedecided the next week that we'd start doing raiding parties, then raid someof the other teams.

Unbeknownst to us, they had been preparing themselves. They had little beaniehats. 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 littlephysical exercise, and had a few laughs. And then we're ready to really goafter it.

ROBERT KRULWICH: The Wagner seems to be working.

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

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

ERIC LANDER: In the past, if you wanted to explain diabetes, you alwayshad to scratch your head and say, 'Well, it might be something else we've neverseen before.' But knowing that you've got the full parts list radically changesbiomedical research, because you can't wave your hands and say, 'It might besomething else.' There is no something else.

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

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

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. Andwhat 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 hairyguys have...you see that? A different spelling.

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

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

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

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

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

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

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

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

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

ROBERT KRULWICH: Kari Stefansson is a Harvard-trainedscientist who saw the potential gold mine that might be hidden in Iceland'sgenetic history. He set up a company called deCODE Genetics to combineage-old family trees with state-of-the-art DNA analysis and computertechnology, and systematically hunt down the genes that causedisease.

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

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

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

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

They got Mrs. Magnusdottir and other members of her family to donate bloodsamples for DNA analysis. And to find more of her relatives, people she'dnever met, deCode just entered her social security number into their giant database, and there they were.

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

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

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

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

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

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

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

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

KARI STEFANSSON: To have all of the data in one place so you can use themodern informatics equipment to juxtapose the bits and pieces of data and lookfor 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 healthcareinformation. We can cross-reference it with DNA information but only from thoseindividuals 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 havedeliberately taken that risk. So it's not imposed on anyone, and no one who isscared of it, no one who is really afraid of it, should come and give usblood.

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

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

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

GATTACA VOICEOVER: 'I'll never understand what possessed mymother to put her faith in God's hands rather than those of her localgeneticist. Ten fingers, ten toes, that's all that used to matter. Notnow. Now, only seconds old, the exact time and cause of my death was alreadyknown.'

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

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

GEORGE ANNAS: That is one possible future—where this becomes so routinethat 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 possiblecrimes in the United States. One copy goes...where? To the grade school? To thehigh school? To the college? To the employer? To the military? Like, a horrificfuture. Although I have to say there are many in the biotech industryand the medical profession who think that's a terrific future.

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

These guys in the funny suits are making gene chips. The little needles aredropping tiny, nearly invisible bits of DNA onto glass slides. And where didthe 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, inprinciple, will allow you to test, say, 1000 babies for 80 different humandiseases. So within a few minutes you can have a readout for thousands or eventens of thousands of babies in a single experiment.

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

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

ROBERT KRULWICH: Well, taking a test and knowing isgreat for the baby or anybody really, as long as there's something you can doabout it. But think about this, because sometimes there may be a test but itmight take 20 years or 50 years...50 years to find a cure. So you couldtake the test and you could learn that there is a disease comingyour 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 goingto get the disease, it will simply say that you may get adisease. And as you know there's a big difference between' you will' and 'youmay.'

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

LISSA KAPUST (Sister of ovarian cancer patient): When my sisterwas diagnosed, my response was disbelief. She was 30 years old. And I'd neverknown anybody of that age to have ovarian cancer.

ROBERT KRULWICH: Melanie fought her cancer for fouryears, 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 only34. But the cancer hadn't spread, so the long-term outlook seemedoptimistic.

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

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

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

ROBERT KRULWICH: When Lissa discovered her secondcancer in 1996, scientists were just beginning to work out the link betweenbreast and ovarian cancers that run in families. Mary-Claire King was one ofthe scientists who discovered that changes or mutations in two specific genesmake 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 2are perfectly healthy, normal genes that all of us have, but in a fewfamilies mutations in these genes are inherited.

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

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 isabout 10 percent over the course of her lifetime, with, of course, most of thatrisk occurring later in her life. For a woman with a mutation in BRCA 1 or BRCA2, the lifetime risk of breast cancer is about 80 percent. It's veryhigh.

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

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

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

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

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

ROBERT KRULWICH: With the second cancer, Lissa had her rightbreast 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 inher left breast. BRCA mutations are relatively rare and only cause maybe fiveor ten percent of all breast cancer. But knowing that there's a BRCAmutation in the family affects everybody.

ERIC KAPUST: The gene doesn't go away. The time passed since the lastcancer 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 ofthis, 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. Herdaughter, Alanna, is 18. There is a fifty-fifty chance that each of them hasinherited the BRCA mutation from Lissa. The only way to know would be to take atest. And when should they do that? When is the right time?

ALANNA KAPUST (Daughter of breast cancer patient): I actuallynever really thought about it until biology this year, when my teacher posed ahypothetical, supposedly, question to people, saying, 'What would you do? Canyou imagine what you would do, if you were faced with the situation where youknew that you might have this disease that would be deadly. Or it would causeyou to be sick and you could do a test that you could find out whether or notyou had it?' And I was sitting there in class saying, 'Maybe it's not sohypothetical.'

ROBERT KRULWICH: And then, in her senior year of highschool, 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 ofmy mind that eventually it may very well happen to me and if it does, thenI'll fight it then. I'll deal with it then. But I don't expect...or Idefinitely didn't expect for this to be happening to me when I was 17 yearsold.

ROBERT KRULWICH: Alanna's lump was not cancer. And fornow she doesn't want the test. Because if she knew that she had the badgene, she'd only have two options: the choice of removing her breasts andovaries to try to reduce her risk or just to be closely monitored andwait.

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

ROBERT KRULWICH: In the next 20 years, this family'spredicament will become more and more common as more and more genes are linkedto more and more diseases and more tests become available. But we willall have to ask, 'Do we want to know?' And when we know, can we live with ananswer that says maybe, but maybe not?

LISSA KAPUST: Driving home from work today, I was tuned in to publicradio and there was a professor of astronomy talking about a brand newtelescope to look into the galaxies. And they're calling it the equivalent ofthe Human Genome Project. And I was thinking, 'Hmm, not quite the equivalent ofthe Human Genome Project.' Because it's without some of the ethical, moralangst—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, andinterventions, and cure.' Versus, 'It's not clear what this all means.'

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

GATTACA GENETIC COUNSELOR: 'Your extracted eggs, Marie,have been fertilized with Antonio's sperm. You have specified hazel eyes, darkhair and fair skin. All that remains is to select the most compatiblecandidate. I've taken the liberty of eradicating any potentially prejudicialconditions: 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 wasgood to leave a few things to chance.'

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

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

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

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

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

Mmm, she threw in some blond hair, too.

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

ERIC LANDER: Well, we don't know. We really don't know how thatengineering occurs and how we can improve on it. It would be very much likegetting a whole pile of parts to a Boeing 777 and a whole pile of parts to anAirbus, and saying, 'Well, I'm going to mix and match some of these so it willhave some of the properties. I make it a little fatter, but I also want to makeit a little shorter.' And by the time you were done you'd think you'd made lotsof 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 apiece...the odds are most changes we would make today, almost all changes we'dmake today, would break the machine.

ROBERT KRULWICH: We may not be able to geneticallymodify humans or Klingons yet, but we do do it to plants and animalsevery day. Look at this stuff: tobacco plants with a gene from a firefly. Andthey used that same insect gene to create glowing mice. So, it's theoreticallypossible that we could create humans with other advantages that borrowed fromother creatures.

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

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

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

TONY WHITE: It changed the paradigm on people, and people don'tlike 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 generationof data. That's what offended people, was that we really felt deeply that thesewere data that had to be available for everybody. And there was an attempt toclaim the public imagination for the proposition that these data were betterdone in some private fashion and owned.

TONY WHITE: You know, you want to say, 'Well, wait a minute. If youcould do it in two years, why weren't you doing it in two years? Why did wehave 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 amountof internal competition, even amongst the academic groups. There's competitionamongst academic scientists to be sure, and more than anything, there'scompetition against disease. There's a strong sense that what we're trying tofind out is the most important information that you could possibly get.

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

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

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

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

ROBERT KRULWICH: President Clinton himself got thepublic guys and the Celera guys to play nice, shake hands, and share the creditfor 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 amagnificent map. The aide was Meriwether Lewis, and the map was the product ofhis courageous expedition across the American frontier all the way to thePacific. Today the world is joining us here in the East Room to behold amap of even greater significance. We are here to celebrate the completion ofthe first survey of the entire human genome. Without a doubt this is the mostimportant, most wondrous map ever produced by humankind.'

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

ERIC LANDER: The genome is very lumpy.

ROBERT KRULWICH: Very lumpy?

ERIC LANDER: Very lumpy, very uneven. You might think, if we have 30,000genes, they're kind of distributed uniformly across the chromosomes. Not so.They're distributed like people are distributed in America: they're all bunchedup in some places, and then you have vast plains that don't have a lot ofpeople in them. It's like that with the genes. There are really gene-denseregions that might have 15 times the density of genes, sort of New York Cityover here. And there are other regions that might go for two million lettersand there's not a gene to be found in there. The remarkable thing about ourgenome 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 notreally yours. It consists of selfish DNA elements that somehow got into ourgenomes 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 ahost for them. They view the human being just as a vehicle for transmittingthemselves.

ROBERT KRULWICH: Wait a second, wait a second, wait asecond. We have in each and every one of our cells that carry DNA, we havethese 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 cansay is stay there and multiply?

ERIC LANDER: Well, they move around.

ROBERT KRULWICH: And what is that? What do you callthat? 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 foritself 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 isthis stuff, not us.

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

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

This gives you a tremendous respect for life. It gives you respect for thecomplexity of life, the innovation of life, and the tremendous connectivityamongst all life on the planet.

ROBERT KRULWICH: We are, in a very real sense, ordinarycreatures. Our parts are interchangeable with all the other animals and eventhe plants around us! And yet we know there is something about us that istruly 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 atwisted staircase. That's what we, and maybe we alone can do.

We can wonder.

Nerf® is a registered trademark of Hasbro, Inc.

Broadcast Credits

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

NOVA Theme

Mason Daring
Martin Brody
Michael Whalen

Post Production Online Editors

Spencer Gentry
Mark Steele

Closed Captioning

The Caption Center

Production Secretaries

Queene Coyne
Linda Callahan

Publicity

Jonathan Renes
Diane Buxton
Katie Kemple

Senior Researcher

Ethan Herberman

Unit Managers

Jessica Maher
Sharon Winsett
Mary Brockmyre

Paralegal

Nancy Marshall

Legal Counsel

Susan Rosen Shishko

Business Manager

Laurie Cahalane

Post Production Assistants

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.

Sources

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.

Cracking Your Genetic Code Video Worksheet

Special Thanks

Cracking Your Genetic Code Video Sheet Answers

Geoff Spencer

National Human Genome Research Institute

Whitehead Institute for Genome Research/MIT:

Dr. Bruce Birren

Dr. Joel Hirschhorn

Seema Kumar