The long-awaited story of the science, the business, the politics, the intrigue behind the scenes of the most ferocious competition in the history of modern science—the race to map the human genome.
On May 10, 1998, biologist Craig Venter, director of the Institute for Genomic Research, announced that he was forming a private company that within three years would unravel the complete genetic code of human life—seven years before the projected finish of the U.S. government’s Human Genome Project. Venter hoped that by decoding the genome ahead of schedule, he would speed up the pace of biomedical research and save the lives of thousands of people. He also hoped to become very famous and very rich. Calling his company Celera (from the Latin for “speed”), he assembled a small group of scientists in an empty building in Rockville, Maryland, and set to work.
At the same time, the leaders of the government program, under the direction of Francis Collins, head of the National Human Genome Research Institute at the National Institutes of Health, began to mobilize an unexpectedly unified effort to beat Venter to the prize—knowledge that had the potential to revolutionize medicine and society.
The stage was set for one of the most thrilling—and important—dramas in the history of science. The Genome War is the definitive account of that drama—the race for the greatest prize biology has had to offer, told by a writer with exclusive access to Venter’s operation from start to finish. It is also the story of how one man’s ambition created a scientific Camelot where, for a moment, it seemed that the competing interests of pure science and commercial profit might be gloriously reconciled—and the national repercussions that resulted when that dream went awry.
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James Shreeve is the author of The Neandertal Enigma: Solving the Mystery of Modern Human Origin, and coauthor of Lucy’s Child: The Discovery of a Human Ancestor. His articles have appeared in The Atlantic Monthly, Discover, National Geographic, Science, Smithsonian, and other publications. He has been a fellow of the Alfred P. Sloan Foundation and of the Alicia Patterson Foundation. Shreeve lives in South Orange, New Jersey.Excerpt. © Reprinted by permission. All rights reserved.:
MAY 1998: "YOU CAN DO MOUSE"
On May 8 of that year, three months before the Nantucket race, Nicholas Wade, a veteran science writer for the New York Times, entered the lobby of the St. Regis hotel on Fifth Avenue. The day before, he had received a call from a public relations representative of the Perkin Elmer Corporation in suburban Connecticut, offering him an exclusive story on an exciting development. Wade was leery. Public relations people often overestimate the media interest in their company's announcements. In the brash, upstart world of biotechnology, moreover, Perkin Elmer was an unglamorous player--a maker of instruments, not news. But the PR rep mentioned that Craig Venter was a player in the new enterprise. Wade knew that Venter would not be involved in anything unglamorous. He agreed to meet with Perkin Elmer's executives over breakfast.
Wade crossed the lobby and squeezed into an elevator just as its doors began to close. A slightly built, mild-mannered Englishman in his fifties, the Times reporter attracted little attention from the dark-suited businessmen already in the elevator. In the Perkin Elmer suite on the fourteenth floor, he was introduced to CEO Tony White and two other company executives. One was Peter Barrett. The other was Michael Hunkapiller, head of Perkin Elmer's Applied Biosystems division, near San Francisco. Wade knew him by reputation. Largely unknown outside the biotech world, Hunkapiller was a legend within it. In the late 1980s, he had co-invented a machine that could automatically sequence DNA--that is, read out the order of a short stretch of chemical letters in the genetic code. Since then his technical genius and business acumen had made him the linchpin of an ongoing effort to develop better, faster instruments for sequencing DNA and speeding up other biotechnical processes.
A lavish breakfast buffet had been set up on a sideboard. Craig Venter was not in the room, but his voice greeted Wade from a speakerphone sitting on a coffee table. "Hey, Nick," he said, in a disarmingly mild tone. "Thanks for coming in so early. There's something we wanted you to be the first to know. Are you sitting down?"
Wade took a chair and opened his notebook. First Venter talked, then Hunkapiller, then Venter again at greater length. Tony White offered an occasional comment, in a broad southern drawl. No one touched the breakfast. Wade sat erect, furiously taking notes. He left an hour and a half later, certain that he had the lead story for the coveted front page of the Sunday edition of the Times.
"Genome" is not a pretty word. Even when you say it in a normal tone of voice, you sound like you're mumbling. It has so recently come into common usage that until 1997, almost a decade after the Human Genome Project began, Microsoft Word's spell-checker assumed that anyone writing about the enterprise had made a typo and corrected it to "the Human Gnome Project." In 1999, bioethicist Arthur Caplan of the University of Pennsylvania was invited to address a meeting of state legislators who were puzzled over the issue of human cloning. Caplan asked the lawmakers if they knew where their genome was located. Roughly one third answered that it was in the brain, and another third thought it was in the gonads. The others weren't sure.
In fact, two copies of your genome--one contributed by each of your parents--are spooled on the twenty-three chromosomes inside the nucleus of every one of your cells--brain, gonad, bone, skin, guts, muscle, mucus, and every other kind of cell, except for red blood. The spool is fantastically compact. Each copy is a double-stranded molecule of DNA only 79 billionths of an inch wide, but which, stretched out, would run almost six feet in length. Upon this attenuated thread--imagine a clothesline running the length of the United States, then back again--lie the chemical instructions that have informed the development of your body and brain from the moment you were conceived. The individual units of instruction are called genes. They are composed of strings of the four chemical bases of DNA: adenine, thymine, guanine, and cytosine--abbreviated A, T, G, and C by scientists. The cell's machinery forms the letters into a series of three-letter words that combined give the recipe for the construction of a specific protein: an enzyme that helps you digest a tuna sandwich, an antibody molecule marshaled to fight off an infection, a receptor protein in your brain that helps you read and understand this paragraph. There are a lot of extra letters in the genome, sloppily referred to as "junk DNA," which do not spell out protein recipes but may serve some other purpose, perhaps vital, perhaps not. The whole human genome contains about 3 billion letters, and is often compared to the text of a book. If you decided to read the book aloud and recited one letter every second, it would take you eleven years to get to the end.
Even if someone had eleven years to spare for such a project, a simple recitation of the DNA letters would give no hint whatsoever of the way the whole genome works to create and operate a human life. Instead of thinking of the genome as a book, imagine it as a piano keyboard. Each piano key represents one gene. If you press down on a key, you hear a single note: the protein that the gene expresses. If you press the key again, you will hear the same note again, monotonously, every time the key is played. But with a piano keyboard, you can do much more than play lots of individual notes. You can combine the notes to make music. Just so, our various cell types play upon the long, thin keyboard of the genome: they combine notes, playing some genes together as chords, tripping several together in a phrase, gathering bundles of notes to create the complex and wonderful effects that find expression in our biological being. Just as a pianist doesn't play all the piano keys in every piece, only some of the genes get played in the cell types of each organ. Sonata in the Key of Kidney. The Heart Fantasia. Variations on the Theme of Brain.
Beautiful music, all of it. But think what can happen to a piano sonata if an important key on the piano sticks, or sounds the wrong note when struck. Such a flaw will ruin every passage in which that key is played. In some cases, it will destroy the music entirely. In the United States, one child out of every four thousand is born with cystic fibrosis, which is caused by a defective gene on chromosome 7. Children with this particular stuck key have abnormally thick mucus in their lungs, leaving them vulnerable to repeated infections that erode the lungs' tissues and eventually the ability to breathe. Most will die before their thirtieth birthday. In another gene, nothing more than a substitution of a T for an A causes sickle-cell anemia. Huntington's disease, a slow, inescapable meltdown of the brain, occurs because a gene near the top of chromosome 4 contains a series of repeated stutters on the letters CAG, playing them over and over like a scratched recording. The patient goes mad and inevitably dies.
Single-gene alterations account for some three thousand to four thousand other inherited diseases. Hard as these defects are to track down, they are by far the easiest targets for gene hunters. Most diseases, including such common killers as cancer and heart disease, stem from disruptions in the interaction among several genes and between genes and the environment. To find their causes, you have to first know what all the keys on the piano are. You have to know the whole genome. This knowledge will not lead directly to a cure for cancer and other killers, but by 1998 even the scientists who had originally opposed the Human Genome Project as ill conceived and not cost-effective were utterly convinced that its fruit would be well worth the $3 billion investment of taxpayer money. The major pharmaceutical companies were betting that it would lead to new drugs worth a whole lot more.
After leaving the St. Regis, Nicholas Wade tried to reach Francis Collins, the head of the government's genome project, whose official title was director of the National Human Genome Research Institute (NHGRI), one of the National Institutes of Health. Collins, more or less against his will, was on a plane headed from Newark to Dulles Airport, where he would catch a flight to Los Angeles. He had originally been scheduled to fly straight from Newark to LA, where he was due to give a lecture the next morning. But the evening before, he had gotten a phone call. The mere sound of Venter's voice on the line gave Collins a shiver of apprehension.
"Francis, I think you need to know about something we're about to announce," Venter said. "We have to meet with you right away."
"Who is 'we'?" Collins asked.
"I can't tell you that," Venter replied. "I don't mean to sound coy. I'm just not authorized to talk about it yet."
The two men had known each other for over a decade. When they were first introduced, Craig Venter was an obscure forty-year-old researcher in the National Institute for Neurological Diseases and Stroke, also part of the NIH. He had not attended college until after service in Vietnam, and thus had begun his career in academic science relatively late. Francis Collins was several years younger but well on his way to becoming perhaps the most famous gene hunter in the world. Soon he would claim a share of the credit for the discovery of five disease-related genes, including two of the most important ones yet found, those responsible for cystic fibrosis and Huntington's disease. In 1994, his success took him to one of the most prominent scientific posts in the country. At the age of forty-three, he was enticed by the secretary of health and human services to leave his large, heavily funded laboratory at the University of Michigan and come to Bethesda, Maryland, to assume leadership of the Human Genome Project, then in its fourth year. The job change meant a cut in pay and much le...
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