The New Explorers. Series III; No. 309; Spiral of Silence

<v Bill Kurtis>A computer is taking us deep inside the cells of a human body, traveling <v Bill Kurtis>through the mast chemicals strands of DNA which determine whether <v Bill Kurtis>a fertilized cell will become a man or woman, dog <v Bill Kurtis>or cat. This is where the secrets of our existence lie. <v Bill Kurtis>The answers to what make our bodies what they are and how they work. <v Bill Kurtis>Our New Explorers are about to embark on a journey inside this amazing world <v Bill Kurtis>to search for a gene in which just 1 pair of molecules out of thousands <v Bill Kurtis>has changed. Mutated. <v Bill Kurtis>Gone wrong. <v Bill Kurtis>What they find will tell them whether this little girl's future lies in a world of sound <v Bill Kurtis>or silence. <v TV Announcer>Major funding for The New Explorers is provided by Amoco celebrating

<v TV Announcer>the adventure of scientific discovery for the year 2000 and beyond. <v TV Announcer>Additional funding is made possible by Waste Management Inc., providing <v TV Announcer>recycling and other waste services around the world. <v TV Announcer>And by Duracell embracing the power of science education, <v TV Announcer>the source of future technology and innovative growth. <v TV Announcer>Duracell, the copper top battery. <v Bill Kurtis>Hello, I'm Bill Kurtis. Here in the heart of Catago, Costa Rica, there was once <v Bill Kurtis>a beautiful church. <v Speaker>[bell tolls] <v Bill Kurtis>When a terrible earthquake destroyed it, the devout people of Cartago rebuilt it stone <v Bill Kurtis>by stone. But when a second earthquake wrecked it, the people said it is <v Bill Kurtis>God's will. And they left it a beautiful ruin. <v Speaker>[chorus sings] <v Bill Kurtis>Since the 18th century, the descendants of Manuel Monge have suffered a strange

<v Bill Kurtis>affliction. Half of every generation has gone deaf. <v Bill Kurtis>Like the earthquakes, some said it, too, was God's will. <v Bill Kurtis>For 9 generations, the Monheit family has lived, worked, and flourished in the town <v Bill Kurtis>of Cartago, Costa Rica. <v Bill Kurtis>From old documents, geneticists have reconstructed the family tree <v Bill Kurtis>through almost 3 centuries. <v Bill Kurtis>The Monge children are born hearing, but for half of them, life is a slow <v Bill Kurtis>journey into silence. <v Bill Kurtis>First, they lose the low tones, the rumble of the trucks, the sounds of thunder <v Bill Kurtis>and drums. <v Bill Kurtis>By 20, the middle tones, the familiar sounds of the human voice disappear.

<v Bill Kurtis>And by about age 30, all is silence. <v Bill Kurtis>Yet despite this enormous handicap, this remarkable family has lived and <v Bill Kurtis>prospered for 9 generations, earning its way, creating jobs <v Bill Kurtis>and small businesses. <v Bill Kurtis>But what went wrong all those generations ago? <v Bill Kurtis>That's what these 2 scientists want to find out. <v Bill Kurtis>One in Central America, the other in North America. <v Bill Kurtis>They're working to piece together the puzzle. <v Bill Kurtis>They determined that the Monge deafness is caused by a single gene. <v Bill Kurtis>Now they have to find it inside another world. <v Bill Kurtis>Their journey will take them into a single human cell, then into the nucleus <v Bill Kurtis>of the cell, and finally into the vast tangled chemicals called DNA,

<v Bill Kurtis>the blueprint of life. <v Bill Kurtis>23 pairs of chromosomes containing all the genes that can dip into <v Bill Kurtis>a soup of chemicals and build a human being. <v Bill Kurtis>It's 1 of the great discoveries of the century. <v Bill Kurtis>Just as 26 letters can spell all the words of our language or 10 digits <v Bill Kurtis>make every number in the universe, so just 4 chemicals arranged <v Bill Kurtis>in pairs repeated 3 billion times spell out the formula <v Bill Kurtis>for a human being. <v Mary-Claire King>In the Monges, we suspect that there's just a single based pair, <v Mary-Claire King>a single element of DNA that's changed that distinguishes <v Mary-Claire King>the Monges' gene from everyone else's gene at this local <v Mary-Claire King>on chromosome 5 [fade out]. <v Bill Kurtis>Mary-Claire King, 1 of the world's leading geneticists, is working on the Monge gene <v Bill Kurtis>from her University of California Berkeley lab. <v Bill Kurtis>King and her researchers are closing in on the gene of breast cancer, on genetic factors <v Bill Kurtis>in AIDS, in the wasting disease of lupus.

<v Bill Kurtis>Even using genetics to reunite kidnaped children, victims of Argentina's dirty <v Bill Kurtis>war, with their families. <v Bill Kurtis>Her partner in Costa Rica, once her student, is geneticist Pedro Leon, <v Bill Kurtis>who first brought the Monge family to the world's attention. <v Pedro Leon>We know that in about 1713, an ancestor to the whole <v Pedro Leon>family was deaf and transmitted the deafness to at least 3 of his children, 2 of <v Pedro Leon>which have descendents today with affected members that we are studying. <v Bill Kurtis>So that ancestor had a mutation in the gene? <v Pedro Leon>That ancestor had a mutation in the gene. <v Bill Kurtis>The Monges seem to fly on the face of evolutionary theory. <v Bill Kurtis>A powerful, harmful mutation, a dominant gene for deafness, has not <v Bill Kurtis>stopped them. <v Pedro Leon>They're very successful in dealing with their- with their social life. <v Pedro Leon>They all marry unaffected people and- and they have many kids. <v Bill Kurtis>And this is the secret of the Monge family success.

<v Bill Kurtis>The way for generations they have beaten evolutionary law. <v Bill Kurtis>Watch. <v Monge Grandfather>[speak Spanish] <v Bill Kurtis>The grandfather can hear. <v Bill Kurtis>So for now, can his grandson. <v Bill Kurtis>Yet he insists that the child watch him as he speaks. <v Bill Kurtis>For 9 generations, every descendant of Manuel Monge has learned <v Bill Kurtis>almost from birth to read lips. <v Bill Kurtis>Since no one knows which child will become deaf, each is taught to watch faces, <v Bill Kurtis>to exaggerate expressions when speaking in the family. <v Bill Kurtis>And even the youngest learn that for a grandmother who is deaf, there is no need <v Bill Kurtis>to make sounds. <v Mary-Claire King>I think for this family, they take deafness as a-

<v Mary-Claire King>as a given in the same way one does black hair. I mean, this is not by any <v Mary-Claire King>means the worst thing that could happen to them. <v Speaker>[speaking Spanish] <v Bill Kurtis>The Monges refuse to learn to sign. <v Bill Kurtis>They say their children must learn to live among the hearing. <v Bill Kurtis>And even when Pedro tries to talk them into using hearing aids, it's an uphill fight. <v Bill Kurtis>[speaking Spanish in background] Pedro isn't trying to get the father to use the hearing <v Bill Kurtis>aid, his hearing is gone. <v Bill Kurtis>But for his teenage daughter, it might mean a few more precious years of hearing. <v Pedro Leon>If they don't do it early on, they will never get used to them and they will reject them. <v Pedro Leon>And that's been our experience. So I think our modest contribution to their <v Pedro Leon>well-being is to convince them that early on a hearing aid will allow them to continue <v Pedro Leon>to go to school, to pursue their professions and so on. <v Bill Kurtis>In Cartago, everyone knows the Monge descendants.

<v Bill Kurtis>They're almost a point of civic pride. <v Bill Kurtis>So Katia and Gabriella Cassada's coworkers automatically adapt to the lip-reading <v Bill Kurtis>mode. <v Katia Cassada>Everybody is very nice with me. <v Katia Cassada>They accept me the way I am and I accept everybody the way people are. <v Katia Cassada>[speaking Spanish in background] For me, human beings don't have to be the same. <v Katia Cassada> And God put this in me. <v Katia Cassada>And for other people, they are blind or they have other problems. <v Katia Cassada>But for me, this is the 1 I have. <v Bill Kurtis>In Katia's generation, <v Bill Kurtis>the Cassadas got a bad roll of the genetic dice. <v Bill Kurtis>Katia, Gabriella, and their brother Javier, all inherited <v Bill Kurtis>the gene. All are going deaf. <v Bill Kurtis>Gabriella communicates with her boyfriend by reading his lips. <v Bill Kurtis>Javier wonders whether his 1-year-old daughter Anna will be spared.

<v Bill Kurtis>He's not sure he wants to know. <v Bill Kurtis>Anna and the next generation are why the family has volunteered to become <v Bill Kurtis>a collective genetic guinea pig. <v Pedro Leon>They will say it openly, they will say me we are doing this for our kids, not for us. <v Pedro Leon>We don't- we don't expect to cured. You don't even know that we want to be cured. <v Pedro Leon>But for our kids, yes. <v Bill Kurtis>It may be that geneticists think a little more about kids, their own kids than <v Bill Kurtis>the rest of us do. <v Bill Kurtis>For Pedro Leon, the fact that his 3 children can all hear, simply hear, <v Bill Kurtis>is a continuing miracle. <v Bill Kurtis>For Mary-Claire King. <v Mary-Claire King>My daughter is- is my proudest accomplishment and anything I do- anything I do <v Mary-Claire King>in- in genetics with my brain doesn't compare remotely to me the importance of my child. <v Mary-Claire King>Um, yeah, my daughter's got great genes, but what I can <v Mary-Claire King>control and what I can give her is a good environment.

<v Mary-Claire King>So to me, the idea of inheritance is not limited to genetic inheritance, <v Mary-Claire King>both for the best things that we can- that we can think about in life, <v Mary-Claire King>we can- we transmit information to the next generation genetically and culturally. <v Mary-Claire King>And to the extent that I can do that with <v Mary-Claire King>my biological child and with these kids in my lab, I think I will have done something <v Mary-Claire King>kind of useful. [background chatter] <v Henriette Raventos>So I have 1 tube for each DNA sample. <v Henriette Raventos>The 11 are 11 of 1 family. <v Henriette Raventos>So we have a father, mother and 9 kids. <v Henriette Raventos>Families like this [fade out] <v Bill Kurtis>Dr. Henriette Raventos, call her ?Jettie? <v Bill Kurtis>At Pedro Leon's lab at the University of Costa Rica, she now <v Bill Kurtis>has the astonishing ability to predict, with better than 90 percent accuracy, <v Bill Kurtis>which children will become deaf and which will not.

<v Bill Kurtis>That's because more than 100 Monge descendants, men, women, children <v Bill Kurtis>have contributed blood samples, their own DNA. <v Bill Kurtis>And the geneticists have been able to isolate the 1 chromosome out of 23 pairs <v Bill Kurtis>that contains the mutated gene, chromosome 5. <v Henriette Raventos>[background chatter] <v Pedro Leon>Over a year ago, we were able to show that all affected members of the <v Pedro Leon>family shared a fairly large region of chromosome 5. <v Pedro Leon>As we increase the sample size and involved new branches of the family, we were able <v Pedro Leon>to narrow that region even more. <v Pedro Leon>And, of course, as we increase our sample size, eventually we narrow the region to a <v Pedro Leon>relatively small, small segment of chromosome 5, which is shared by all the affected <v Pedro Leon>members, but it's not present in the unaffected. <v Bill Kurtis>Katia, Gabriella, and Javier all contributed their DNA <v Bill Kurtis>and all show the signature pattern on chromosome 5.

<v Bill Kurtis>And that in turn leads to the next crucial moment in this scientific detective story. <v Bill Kurtis>Prediction. <v Henriette Raventos>So now I have the DNA in- in the tubes. <v Henriette Raventos>Now I'm going to make a mix that will contain all the ingredients <v Henriette Raventos>necessary for the PCR. <v Bill Kurtis>The same method that located the deafness gene on chromosome 5 just a year ago <v Bill Kurtis>now gives scientists the power to predict who in the family will go deaf. <v Bill Kurtis>The secret is a new genetic technique called PCR, polymerase chain reaction, <v Bill Kurtis>which can turn one tiny fragment of DNA into thousands of identical copies. <v Henriette Raventos>This is the PCR machine. <v Henriette Raventos>The first thing it will do is heat up the samples <v Henriette Raventos>a- to a temperature where the DNA will- the 2 bands will open <v Henriette Raventos>up. What the PCR does is that <v Henriette Raventos>if you have 1 molecule of DNA, after 1 cycle,

<v Henriette Raventos>you'll have 2. After the second cycle, you'll have 4. <v Henriette Raventos>After the third cycle, you'll have 8. <v Henriette Raventos>And so on. <v Bill Kurtis>A geometric progression. <v Henriette Raventos>Right. So at the end of the 25 cycles, you'll have <v Henriette Raventos>thousands of copies just of that small window. <v Bill Kurtis>I can see the little [fade out]. <v Bill Kurtis>With thousands of copies of the DNA from mother, father, and 9 children, Jettie <v Bill Kurtis>drops the samples into tiny wells in a gel and passes an electric current <v Bill Kurtis>through them. DNA has a slight negative charge, so each part will move through <v Bill Kurtis>the gel at a different speed depending on its weight. <v Bill Kurtis>And by comparing DNA from more than 100 Monges, hearing and <v Bill Kurtis>deaf, these scientists now know which lines in the gel betray <v Bill Kurtis>that strange and powerful gene, the Monge deafness. <v Henriette Raventos>This is the gell that has been already run around 18 hours and ?it does <v Henriette Raventos>stain?. So we can see now the amplified regions.

<v Bill Kurtis>Well, let's see what we have. <v Henriette Raventos>In this case, we can tell only that this 1 will become deaf <v Henriette Raventos>and this 1 will not become deaf. <v Bill Kurtis>Now, what about little Anna? Can you predict if she will become deaf? <v Pedro Leon>We can predict with about 95 percent certainty whether Anna will be deaf <v Pedro Leon>or not. I don't know if they want to know and I'm not sure that <v Pedro Leon>we want to do it until we're certain that the family is prepared to deal with that <v Pedro Leon>knowledge appropriately and not uh change their behavior negatively towards <v Pedro Leon>any of the kids that might be deaf later on. <v Bill Kurtis>It's also difficult, isn't it, to tell someone they're going to be deaf and not be able <v Bill Kurtis>to tell them that there's a cure? <v Pedro Leon>That's right. That's right. <v Mary-Claire King>The most serious ethical dilemma that we face in human genetics now <v Mary-Claire King>is the gap between being able to predict who will develop various <v Mary-Claire King>conditions, which we can do now. We can do that for the Monges, for deafness.

<v Mary-Claire King>We can do that for many families for breast cancer. <v Mary-Claire King>We can do that for many, many conditions and our ability to actually do something <v Mary-Claire King>about that. The critical question is, how do you close the gap? <v Mary-Claire King>And the way you close the gap is to find the gene. <v Mary-Claire King>And when you've found the gene, then you can learn what that gene does and you can learn <v Mary-Claire King>how to change the mutant or abnormal form of that gene <v Mary-Claire King>so that you replace the abnormal product with a normal product. <v Bill Kurtis>For the Monges, the next step is to find out how the mutated gene makes them <v Bill Kurtis>go deaf. Does it affect the bones of the middle ear? <v Bill Kurtis>The drum? The auditory nerve? <v Bill Kurtis>Pedro Leon has brought 3 of the family members to San Francisco for some advanced <v Bill Kurtis>ear testing to find out. <v Bill Kurtis>But before the tests, there is a sight-seeing.

<v Bill Kurtis>Beneath the Golden Gate, Katia, her cousin Adolfo, and his 6-year-old <v Bill Kurtis>son Eric pause for pictures. <v Bill Kurtis>They've never been outside Costa Rica. <v Bill Kurtis>Eric can still hear the thunder and the crash of the long Pacific rollers. <v Bill Kurtis>To Katia, at 22, they're a distant hiss. <v Bill Kurtis>To Adolpho, past 30, something even less. <v Robert Jackler>And what we can see is 3-dimensional view of the eardrum. <v Robert Jackler>Gracias. [fade out]. <v Bill Kurtis>At the University of San Francisco hearing lab, Dr. Robert Jackler begins work on Adolfo. <v Robert Jackler>And as expected, the eardrum looks normal. <v Robert Jackler>There's the drum. There, can you see? [laughs] <v Bill Kurtis>Eric is being prepped for a CAT scan.

<v Bill Kurtis>This giant x-ray machine will make 3-D drawings of his entire ear <v Bill Kurtis>structure. <v Speaker>[speaking Spanish]. <v Bill Kurtis>Because the organs of hearing are so intimately linked with the semicircular canals of <v Bill Kurtis>balance, the San Francisco researchers want to see whether there's any effect on Katia's <v Bill Kurtis>equilibrium. <v Robert Jackler>Can you see the eyes jumping? It tells us that her inner ears are <v Robert Jackler>sensing motion. And it's the motion of the fluid within the balance canals that <v Robert Jackler>is continuing its momentum and that uh it lasts for a few moments. <v Robert Jackler>So what it tells us is, although she has a very severe hearing loss, is that the balance <v Robert Jackler>side of the inner ear seems to be functioning, at least to some degree. <v Bill Kurtis>Later, much more delicate tests will confirm. <v Bill Kurtis>There's nothing wrong with Monge ears except that they go deaf. <v Doctor>Eric, ?decir? Mesa.

<v Eric>Mesa. <v Doctor>?Decir? Cinco. <v Eric>Cinco. Aqua. <v Bill Kurtis>Through 2 grueling days, the doctors mix standard hearing tests with <v Bill Kurtis>the most sophisticated techniques. <v Bill Kurtis>This is a scan of Eric's brainwaves to see whether sound ever reaches his auditory <v Bill Kurtis>nerve. Fascinating for the scientist. <v Bill Kurtis>A bit dull for a 6-year-old. <v Doctor>It looks like at this particular frequency, he does have some hair cells <v Doctor>or some nerve cells that are still firing and still working in a pretty <v Doctor>good manner. <v Doctor>This test procedure is just fantastic. <v Doctor>The information this is giving me 2 years ago, we never could have gotten on <v Doctor>anybody. <v Bill Kurtis>The bottom line for the Monge deafness, deep inside the cochlea, the inner <v Bill Kurtis>ear organ of hearing, lie rows of tiny nerves called hair cells, thousands

<v Bill Kurtis>of them. And Manuel Monge's descendants, the delicate hair cells stop responding <v Bill Kurtis>to sound, either because something goes wrong with them or because the transparent <v Bill Kurtis>fluid in which they live and work thickens up. <v Bill Kurtis>That is the legacy of the Monge mutated gene. <v Bill Kurtis>Now it's up to the scientists to find a way to switch it back on. <v Mary-Claire King>For us as geneticists, there's both the hope and the absolute commitment <v Mary-Claire King>to closing the gap between being able to predict who will <v Mary-Claire King>develop 1 or another condition that- that we're mapping and <v Mary-Claire King>being able to offer a cure or absolute prevention. <v Bill Kurtis>While they're in California, Katia, Adolfo, and Eric go to visit Mary-Claire King and <v Bill Kurtis>see the Berkeley lab where she's trying to map the gene that is taking away their <v Bill Kurtis>hearing.

<v Bill Kurtis>Here in this freezer, the DNA of Manuel Monge's descendants, cloned now, <v Bill Kurtis>so the supply will never run out. <v Bill Kurtis>Short fragments of chromosome 5 from more than 100 family members. <v Bill Kurtis>Half of them carry the Monge gene. <v Mary-Claire King>[speaking Spanish] <v Bill Kurtis>This is the key. The genetic map of more than 100 descendants <v Bill Kurtis>of Manuel Monge. <v Mary-Claire King>[speaking Spanish] <v Bill Kurtis>6-year-old Eric sees himself a square because he's a male. <v Bill Kurtis>A blackened square because he has the gene. <v Bill Kurtis>[Spanish in background] In each set of parents, <v Bill Kurtis>1 blacked-out symbol, the carrier of the Monge gene. <v Bill Kurtis>[Spanish in background] <v Bill Kurtis>And every blackened symbol shares the same short strip of DNA marked with a

<v Bill Kurtis>box, perhaps a dozen genes on chromosome 5, which include <v Bill Kurtis>the Monge deafness gene. <v Bill Kurtis>Mary-Claire King and Pedro Leon are now in the homestretch. <v Bill Kurtis>Like geographers, they have begun to chart the territory of the Monge gene. <v Bill Kurtis>Next, they will try to find a method in both its normal and mutated <v Bill Kurtis>form that they say will be the great breakthrough, the beginning of the end, <v Bill Kurtis>perhaps, of this journey through 3 centuries and 2 worlds. <v Mary-Claire King>Then we'll know what this gene does normally. <v Mary-Claire King>And of course, we'll know what it does in its mutant form. <v Mary-Claire King>And those 2 pieces of information will be absolutely critical to <v Mary-Claire King>being able to offer a cure or to being able to prevent deafness from <v Mary-Claire King>beginning in the first place. <v Bill Kurtis>These New Explorers believe they've gotten hold of a sort of scientific philosopher's

<v Bill Kurtis>stone, that the same techniques hold the key to curing and <v Bill Kurtis>preventing a host of devastating genetic ills. <v Bill Kurtis>Perhaps sooner than we think. <v Mary-Claire King>Gene therapy is not, to me, a matter of manipulating what <v Mary-Claire King>our children will be like. Gene therapy is the use of genetics <v Mary-Claire King>for medical purposes. The use of genetics to both determine <v Mary-Claire King>what the best kinds of medicines will be and the use of genetics to- <v Mary-Claire King>to actually introduce those medications to the organism, to <v Mary-Claire King>ourselves, to fix whatever it is that's gone wrong. <v Mary-Claire King>Working on the soma, on the body, of the individual with the illness is going to be <v Mary-Claire King>revolutionized in the next 5 years. And I anticipate that we'll be <v Mary-Claire King>using it for- for the Monge deafness, for Huntington's disease, for breast cancer, <v Mary-Claire King>for a wide variety of important human traits.

<v Bill Kurtis>The gift of the Monges may be a gift to all of our children, not just their own. <v Bill Kurtis>And what about Anna? Pedro Leon knows whether or not he is fated to go deaf, <v Bill Kurtis>but her family has not yet asked. <v TV Announcer>Major funding for The New Explorers is provided by Amoco, celebrating <v TV Announcer>the adventure of scientific discovery for the year 2000 and beyond.

<v TV Announcer>Additional funding is made possible by Waste Management Inc., providing <v TV Announcer>recycling and other waste services around the world. <v TV Announcer>And by Duracell embracing the power of science education, <v TV Announcer>the source of future technology and innovative growth. <v TV Announcer>Duracell, the copper top battery. <v TV Announcer 2>A videocassette and accompanying teacher's guide are available for each episode of The <v TV Announcer 2>New Explorers. To order, call 1 800 6 2 1 0 6 6 0, or write <v TV Announcer 2>The New Explorers, 1 5 1 8 1, Route 58 South, Oberlin, Ohio, <v TV Announcer 2>4 4 0 7 4. <v PBS Announcer>This is PBS.