Nova Cracking The Code Of Life A Family Disease
Jasmine Lemaitre
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.
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: 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.
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.
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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: 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.
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.
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.
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: 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 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.
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.
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.
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: 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.
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.
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.
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