a NewsHour with Jim Lehrer Transcript
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GENOME UNRAVELED

June 26, 2000

Experts discuss the future of genetic research and how it could change medicine, after this background report.

The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.

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An Online Focus on Genetic Research

The Online NewsHour Health Spotlight

June 16, 2000:
The Race to Sequence the Genome

Extended Excerpts:
J. Craig Venter
Francis Collins

Stelios Papadapoulos

April 6, 2000:
Sequencing the Genome

March 21, 2000:
Author Matt Ridley in an Online Forum about the Human Genome Project.

March 16, 2000:
Should companies be able to use findings on the human genome for profit?

February 29, 2000:
Author Matt Ridley and his book on the human genome

February 2, 2000:
Does gene therapy have harmful side affects?

December 8, 1999:
The growing gene therapy controversy.

December 2, 1999:
Progress in deciphering the human genome.

July 10, 1998:
Do DNA databanks violate the rights of defendants?

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Celera Genomics

The National Human Genome Research Institute

 

JIM LEHRER: Breaking the genetic code. Susan Dentzer of our health unit begins. The unit is a partnership with the Henry J. Kaiser Family Foundation.

SUSAN DENTZER: At today's joint U.S. and British news conference, President Clinton, Prime Minister Tony Blair, and the assembled scientists heralded the event as an unparalleled breakthrough.

PRESIDENT CLINTON: We are here to celebrate the completion of the first survey of the entire human genome. Without a doubt this is the most important, most wondrous map ever produced by humankind.

SUSAN DENTZER: By satellite, Prime Minister Blair called it the start of a new era when scientists could begin to fight human disease at its most basic genetic roots.

TONY BLAIR: Let us be in no doubt about what we are witnessing today, a revolution in medical science whose implications far surpass even the discovery of antibiotics; the first great technological triumph of the 21st century.

SUSAN DENTZER: The President then laid out where that revolution might lead, now and in the decades to come.

PRESIDENT CLINTON: With this profound new knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on all our lives and even more on the lives of our children. It will revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer's, Parkinson's, diabetes, and cancer by attacking their genetic roots.

 
Two competing interests

SUSAN DENTZER: Flanking the president were representatives of the two groups that produced the two separate blueprints of the genome. One was Dr. Francis Collins, who heads the international public and private research consortium known as the Human Genome Project. Today it announced a working draft of the genome that was roughly 85% complete. The other was J. Craig Venter, president of the private U.S. firm Celera Genomics. It announced last April that it had decoded the entire genome and reported today that final assembly of its version was complete. The presence of both men marked an important symbolic truce in a long-running rivalry between the two groups to sequence the genome first. Collins spoke glowingly of Venter's contributions.

DR. FRANCIS COLLINS: I congratulate him and his team on the work done at Celera, which uses an elegant and innovative strategy that is highly complementary to the approach taken by the public project. Much will be learned from a comparison of the two. I'm happy that today the only race we are talking about is the human race.

SUSAN DENTZER: In turn, Venter was equally complimentary of his former rivals, and of massive public investments in research that the private sector had built on.

J. CRAIG VENTER: The completion of the human genetic blueprint would not have been possible without the continued investment of the U.S. government in basic research. I applaud the president's efforts and the work of Congress during the last several years in producing the largest funding increases to fuel the engines of basic science. At the same time, we could not overlook the investment of the private sector in research in America.

SUSAN DENTZER: Just what does it mean to have sequenced the genome? Most of us know that humans have 80,000 or more genes distributed along 23 pairs of chromosomes like these. We probably learned in school that these genes determine man of our features, such as whether our eyes are blue or brown. But what we may not have mastered is how genes produce these attributes or determine the body's other functions. Here's how that works.

Our genes, copies of which are in most of our cells, are made up of DNA. As diagrammed by scientists, in its chemical structure DNA looks like a twisted ladder, or a double helix. The rungs of the DNA ladder are made up of four chemicals, whose names begin with the initials "a," "t," "g," and "c." These chemicals, or letters, pair up, and a total of 3.2 billion pairs make up our DNA. We don't know, at least yet, what the vast percentage of the DNA does. But we do know that a small portion of our genes function like tiny factories. In a complicated way, the "a," "t," "g," and "c" chemicals in the DNA copy themselves many times over to produce the proteins that carry out most of the body's vital work. So when we talk about sequencing the entire human genome, we mean figuring out exactly how all three billion pairs of these letters are arrayed, in large part to make this protein-manufacturing process possible. Francis Collins says a whole new world of genetic research began to open up in the 1980s.

Potential revolution in biology
DR. FRANCIS COLLINS: Some visionary folks -- some people called them dreamers, some people called them nuts -- began to contemplate the idea that we might, in an organized fashion, actually try to map and sequence all of the human DNA, not 50 or 100 years from now, but in an organized effort maybe over the course of 15 or 20 years. That was very hotly debated.

SUSAN DENTZER: For one thing, these were the days before much of the labor-saving technology used to sequence the genome was even available, such as robots or very high-speed supercomputers. Stanford geneticist David Botstein says the costs seemed likely to reach billions of dollars before the job was done.

DAVID BOTSTEIN: Many scientists, including me, had real doubts. But at the same time, even the most dedicated opponents understood that actually knowing the whole genome was going to be in itself a very valuable, potentially revolutionary thing in biology.

SUSAN DENTZER: Botstein was among those eventually appointed to a scientific panel that drew up a plan to tackle the project. First, to gain more knowledge and skill, scientists would decode the genomes of simpler organisms, like the fruit fly, that still had plenty in common with humans' genetic makeup. Botstein headed a project to sequence the genome of one organism, the yeast.

DAVID BOTSTEIN: The idea was to take advantage of the fact that evolution has been very slow, relatively, and to sequence a few simple organisms with very small genomes where the genes are much better understood.

SUSAN DENTZER: In the meantime, the hope was that the technology to carry out gene sequencing would improve and costs would drop. After the plan was hammered out, the human genome project was officially launched. That's an international consortium of academic and other researchers led by the United States and Britain. Collins says the group's first task was to draw up a so-called map of the human genome.

DR. FRANCIS COLLINS: If the genome is sort of like the United States, and each chromosome is a different state, it was to try to lay out where in fact are the major landmarks, the mountain ranges, the major cities, a few of the small towns.

SUSAN DENTZER: Literally that meant breaking all of human DNA up into sections that were roughly 35,000 letters long, then trying to figure out how these chunks were distributed along our chromosomes. With that job accomplished, Collins says the group turned to the tougher task of gene sequencing, or figuring out how each of the more-than three billion pairs of letters was arranged.

DR. FRANCIS COLLINS: That is in many ways, you might imagine, a mind-numbing experience, and it is done primarily by automated instruments.

SUSAN DENTZER: In fact, by this point technology was advancing fast enough to make this sequencing possible. And it was about to take an even greater leap forward.

J. CRAIG VENTER: So we basically, per day here, sequence 100,000 to 200,000 samples, each one giving us about 600 letters of genetic code, 24 hours a day, seven days a week.

SUSAN DENTZER: Craig Venter, formerly a biochemist at the National Institutes of Health, was running a private genomics research institute in the mid-1990s One day he got a call out of the blue from a private company.

J. CRAIG VENTER: They had an exciting new technology, and they wanted me to see it, and they were also thinking of putting up all the money to sequence the genome, the human genome, and was I interested?

SUSAN DENTZER: With a combination of lasers and other high-tech tools, the machines could actually distinguish samples of DNA letter by letter, producing a sequence as long as several thousand letters in a three-hour run.

J. CRAIG VENTER: We spent a day looking at the prototype machines they had. By the end of that day, we had a plan to sequence the human genome within a two-year period.

SUSAN DENTZER: In effect, Venter and his backers had dreamed up a shortcut to sequencing the genome with the aid of automatic sequencers, supercomputers, and mathematical tools. The company they founded to do that was Celera Genomics.

J. CRAIG VENTER: We reasoned that we could take the chromosome, break it up into small pieces, sequence the 500 to 600 letters at a time, and then use the computer to basically solve a jigsaw puzzle.

SUSAN DENTZER: In 1998, Venter's group approached Francis Collins and offered to bring the new technology and tactics to work on the Human Genome Project. At the time, the consortium's own sequencing efforts seemed likely to take another ten years. But in the end, Venter and his colleagues were rebuffed. So Venter and his new company, Celera Genomics, went their own way. That culminated in Celera's announcement last April. The company had met its own two-year deadline and arguably stood to win the sequencing race.

A race for knowledge
J. CRAIG VENTER: I think you'll find most people in this field will honestly tell you that would have been 10 years away if it wasn't for Celera.

SUSAN DENTZER: How much the two versions of the genome differ will only be clear once the two are published in a scientific journal later this year. Collins and Venter said today that they'll also hold a historic joint conference, possibly next fall, at which scientists from all over the world will be invited to pore over both versions and attempt the critical work of identifying actual human genes. Both sides will also post their entire versions of the genome on the Internet. Researchers around the world are losing no time putting the new genomics knowledge to work. An especially fruitful area of research is looking for misspellings in genetic letters that can help cause disease. In fact, according to some estimates, 10,000 or more new drugs derived from genetic discoveries could be on the market in coming years. Even as scientists saluted that prospect today, they also raised concerns that the benefits of our growing genetic knowledge could be denied to some. And Collins warned that it could serve as a basis for denying health insurance coverage or other forms of discrimination.

DR. FRANCIS COLLINS: Maybe a couple of years ago you could say it was still up the track there and we could take our time. But it's bearing down on us and we ought to do the right thing here and pass those kinds of protections so that people will not be afraid to have genetic information that could be of enormous value to them a determinant for fear that it might be used against them.

SUSAN DENTZER: President Clinton agreed, underscoring how much the genome reflected our similarities more than our differences.

PRESIDENT CLINTON: I believe one of the great truths to emerge from this triumphant expedition inside the Human Genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 percent the same. What that means is that modern science has confirmed what we first learned from ancient fates: The most important fact of life on this earth is our common humanity.