Panic in Level 4

by Richard Preston

  Smith passed a computer, stopped, and brought up a quote. Celera had finally opened for trading. It had gapped upward—that is, it had jumped instantly upward—by thirteen points. It was at 114. Smith’s net worth had jumped upward by around a million dollars in ten seconds. “Is there no end to this?” he muttered.

  Craig Venter came into Smith’s lab and asked him to lunch. In the elevator, Smith said to him, “I can’t stand it, Craig. The bubble will break.” They sat down beside each other in the cafeteria and ate cassoulet from bowls on trays.

  “This defies common sense,” Smith went on. “It’s really impossible to put a value on this company.”

  “That’s what we’ve been telling the analysts,” Venter said.

  Later that day, I ended up in Claire Fraser’s office at TIGR headquarters, a complex of semi–Mission style buildings a couple of miles from Celera’s offices and labs. Fraser, who was then Venter’s wife, was a tall, reserved woman with dark hair and brown eyes, and her voice had a New England accent. She grew up in Massachusetts. In high school, she said, she was considered a science geek. Her office had an Oriental rug on the floor and a table surrounded by Chippendale chairs. (“This is Craig’s extravagant taste, not mine,” she explained.) Two poodles, Shadow and Marley, slept by a fireplace.

  “Before genomics, every living organism was a black box,” she said. “When you sequence a genome, it’s like walking into a dark room and turning on a light. You see entirely new things everywhere.”

  Fraser placed a sheet of paper on the table. It contained an impossibly complicated diagram that looked like a design for an oil refinery. She explained that it was an analysis of the genome of cholera, a single-celled microbe that causes murderous diarrhea; TIGR scientists had finished sequencing the organism’s DNA a few weeks earlier. Much of the picture, she said, was absolutely new to our knowledge of life. About a quarter of the genes of every microbe that had been decoded by TIGR were completely new to science and were not obviously related to any other gene in any other microbe. To the intense surprise and wonder of the scientists, nature was turning out to be an uncharted sea of unknown genes. The code of life was far richer and more beautiful than anyone had imagined.

  Fraser’s eyes moved quickly over the diagram. In effect, she was seeing cholera for the first time in the history of biology. And she could sight-read the diagram, in the same way that a good musician can sight-read Mozart and hear it in her head. “Yes…wow…,” Fraser murmured. “Wow. There may be important transporters here…. It looks like there could be potential for designing a new drug that could block them.”

  The phone rang. Fraser walked across her office, picked up the receiver, and said softly, “Craig? Hello. What? It closed at a hundred and twenty-five?” Pause. “I don’t know how much it’s worth. You’re the one with the calculator.”

  Their net worth had jumped above $150 million that day.

  Fraser drove home, and I followed her in my car. The house she shared with Venter was in a wealthy neighborhood outside Washington. It sat behind a security gate at the end of a long driveway. Venter arrived in a brand-new Porsche. The car would do zero to sixty in five seconds, he said. In the vaulted front hall of the house there was a model of HMS Victory in a glass case. In a room next to the garage, there was a jumble of woodworking machines—a band saw, a table saw, a drill press. Venter had worked with wood since his shop classes in high school.

  In the kitchen, Claire fixed dinner for the poodles, while Craig circled the room, talking. “We created close to two hundred millionaires in the company today. I think most of them had not a clue this would happen when they joined Celera. We have a secretary who became a millionaire today. She’s married to a retired policeman. He went out looking to buy a farm.” He popped a Bud Light and swigged it. “This could only happen in America. You’ve got to love this country.” Claire fed the poodles.

  There were no cooking tools in the kitchen that I could see. The counters were empty. The only food I noticed was a giant sack of dog food, sitting on top of an island counter, and two boxes of cold cereal—Quaker Oatmeal Squares and Total. In the guest bathroom, upstairs, there were no towels, and the walls were empty. The only decorative object in the bathroom was a cheap wicker basket piled with little soaps and shampoos they had picked up in hotels.

  We went to a restaurant and ate steak. “We’re in the Wild West of genomics,” Venter said. “Celera is more than a scientific experiment; it’s a business experiment. Our stock-market capitalization as of today is three and a half billion dollars. That’s more than the projected cost of the Human Genome Project. I guess that’s saying something. The combined market value of the Big Three genomics companies—Celera, Human Genome Sciences, and Incyte—was about twelve billion dollars at the end of today. This wasn’t imaginable six months ago. The Old Guard doesn’t have control of genomics anymore.” He chewed steak and looked at his wife. “What the hell are we going to do with all this money? I could play around with boats…”

  Claire started laughing. “My God, I couldn’t live with you.”

  “The money’s nice, but it’s not the motivation,” Venter said to me. “The motivation is sheer curiosity.”

  In December, Celera and the Human Genome Project discussed whether it would be possible to collaborate. There was one formal meeting, and there were many points of difference. Meanwhile, Celera’s stock seemed to go into escape velocity. In January, it soared to over $200 a share. Celera filed to offer more shares to the public and declared a two-for-one stock split. Shortly after the split, the stock hit an all-time high of $276 a share (adjusted for the split). Celera’s stock-market value reached $20 billion, and Craig Venter’s wealth on paper surpassed $1 billion. It looked as though Craig Venter had become the first billionaire of biotechnology.

  * * *

  FRANCIS COLLINS, the director of the National Institutes of Health’s part of the Human Genome Project—in actuality, he was the principal leader of the project—was a Christian who drove to work on a motorcycle. He played guitar in an amateur rock band. He was six feet four inches tall. He had expressive hands that moved while he spoke, and he had a soft, expressive voice. He wore faded jeans and motocycle boots or sneakers. His net worth was not impressive, because his employer was the government. He had a mop of graying brown hair combed over his forehead. Collins had grown up on a small farm in the Shenandoah Valley, where he’d been homeschooled by his mother, Margaret Collins, a noted American playwright, and by his father, Fletcher, a medieval scholar and founder of several theater troupes. Francis Collins went to Yale, where he got a PhD in quantum chemistry, but then he decided to become a medical doctor.

  “My epiphany came two months into medical school, when I listened to a series of lectures on genetic diseases by an austere and impressive pediatric geneticist,” Collins told me in his office on the campus of the National Institutes of Health, in Bethesda, Maryland. “Each week he brought a different child in front of the class, with a different genetic disease—cystic fibrosis, sickle-cell anemia. They’re sick, I thought, because they have a single little thing wrong in the arrangement of their code. It was almost unbelievable that such a small change could have such large effects in some people. It was terrifying.”

  “Have you heard of Lesch-Nyhan syndrome?” I asked Collins, referring to the self-cannibalism disease. It is caused by a tiny defect in the human DNA, typically the alteration of a single letter of the human genome.

  Francis Collins had certainly heard of the disease. He had seen it. “I diagnosed a case of Lesch-Nyhan syndrome when I was at Yale medical school,” Collins said. “He was a young man, twenty-four years old, and he was engaging in self-mutiliation. I’ve thought a lot about Lesch-Nyhan syndrome. Why would a loving God allow the kind of suffering we see in a Lesch-Nyhan person? Why would God permit a loss of free will in these people? These are tough questions. We tend to see our suffering as a consequence of our own free-will choices. But when the suffering comes
from a little glitch in our DNA, how is that compatible with a loving God? I can’t say that I have the answers. Perhaps there is an answer in John, chapter nine, when Christ and his disciples pass by a child who is blind. One of the disciples asks, ‘Master, who sinned that this child was born blind? Was it the child or his parents?’ Christ answered, ‘Neither have sinned. He is blind so that the nature of God might be manifest in him.’ We don’t learn much when life is too easy; God shouts at us in the tough times. Even so, I’m not sure that Christ’s answer makes me comfortable with a child with a genetic disease. I’ve spent way too much time in hospitals with families and patients, putting names to diseases that I couldn’t do a thing about. Who knows what lurks in our DNA?”

  Francis Collins stretched out his long frame, sticking his legs out straight, and crossed his sneakers. “Sequencing a gene is one thing, but reading the whole human genome—that could never have been imagined. Between splitting the atom, and going to the moon, and reading the human DNA, I would argue that this last will go down in history as the most important. This simple code, with its amazing properties, which unifies all living forms…” His voice trailed off. “It carries me away.”

  * * *

  RIGHT AROUND THE TIME I spoke with Francis Collins, newspapers reported that the discussions between Celera and the public project had collapsed. It seems that the discussions had been going on via the two main principals, Craig Venter and Francis Collins. The toughest point of disagreement, according to officials at the public project, was that Celera wanted to keep control of intellectual property in the human genome, while Francis Collins and the other leaders of the Human Genome Project were determined to let the information be available to anyone for free. Celera’s stock began to drop.

  Then it went into a screaming nosedive. It dropped fifty-seven dollars in a matter of hours, lurching downward. On the floor of the New York Stock Exchange, the traders were holding fistfuls of sell slips for Celera, and nobody wanted to buy the stock. The other genomic stocks crashed in sympathy with Celera. This, in turn, dragged down the NASDAQ, which that day suffered the second-largest point loss in its history.

  It was, in fact, a more generalized heart attack affecting the entire American stock market. This was the popping of the Internet stock-market bubble. It ushered in a bear market, a period of years in which the stock market went down or sideways. Not merely Internet stocks were crashing; everything that had anything to do with technology was falling in value. In the end, just about anything that had to do with the Internet was crushed, and many stocks lost 90 to 100 percent of their value. Short sellers—people who profit from the decline of a stock—had encrusted Celera’s stock like locusts. Craig Venter seemed to be one of the forces bringing the stock market down.

  “I feel a little like Galileo. I’m expecting a call from the pope any day now, asking me to recant the human genome,” Venter said to me right after Celera’s stock had gone over the lip of Niagara Falls in a barrel. He sounded wired and exhausted. “They offered to have a barbecue with Galileo, right? Look, I’m not likening myself to Galileo in terms of genius, but it is clear that the human genome is the science event of our time. I am going to publish the human genome, and that’s what the threat to the public order is. Our publishing the genome makes a mockery of the fifteen years and billions of dollars the public project has spent on it.”

  Venter seemed particularly upset with the British part of the public project. “In my opinion,” he said, “the Wellcome Trust is now trying to justify how, as a private charity, it gave what I think was well over a billion dollars to do just a third of the human genome, largely at the expense of the rest of British medical science. Forty billion dollars was taken out of the biotechnology industry today—that’s how much was lost by investors in all the biotechnology companies. It was money that would pay for cures for cancer, and it was taken off the table, all because some bastards at the Wellcome Trust are trying to cover up their losses.”

  I called Michael Morgan, at the Wellcome Trust, to see what he had to say about this. “In hindsight, it is easy to ascribe to us Machiavellian powers that the prince would have been proud of,” he said dryly. “As for the allegation that I’m a bastard, I can easily disprove it using the technology of the Human Genome Project.”

  * * *

  “ONE OF THE THINGS I really like about Craig Venter is that he almost totally lacks tact,” one of his collaborators, a genomic scientist from U.C. Berkeley, Gerald Rubin, told me. “If he thinks you are an idiot, he will say so. I find that way of dealing very enjoyable. Craig is like somebody who’s using the wrong fork at a fancy dinner. He’ll tell you what he thinks of the food, but he won’t even think about what fork he’s using. It was a great collaboration.”

  John Sulston, the head of the Sanger Centre, told the BBC that he felt Celera planned to try to get a monopoly on the human DNA. “The emerging truth is absolutely extraordinary,” Sulston said. “They really do intend to establish a complete monopoly position on the human genome for a period of at least five years.” He added, “It’s something of a con job.”

  “Sulston essentially called us a fraud. It’s like he’s been bit by a rabid animal,” Venter fumed.

  “It’s puzzling. To me, the whole fight defies rational analysis,” Nobel laureate Hamilton Smith said to me, shortly after his net worth had cratered in Celera’s mud slide. (He had continued to drive his ’83 Marquis, so his lifestyle had not been much affected.) “But the publicly funded labs are angry for reasons I can partly understand,” Smith went on. “We took it away from them. We took the big prize away from them, when they thought they would be the team that would do the whole human genome and go down in history. Pure and simple, they hate us.”

  * * *

  AS FOR THE SCIENCE, most biologists seemed enthralled with the sight of the human DNA being decoded and revealed. They felt that a great door was opening and light was shining deep into nature, suggesting the presence of rooms upon rooms that had never been seen before. There was also a clear sense that the door would not have been opened so soon if Craig Venter and Celera had not given it a swift kick.

  “We can thank Venter in retrospect,” James Watson said, leaning back and smiling and squinting at the ceiling. “I was worried he could do it, and that would stop public funding of the Human Genome Project…but if an earthquake suddenly rattled through Rockville and destroyed Celera’s computers, it wouldn’t make much difference….” His voice trailed off. He stood up and offered me the door.

  Eric Lander, who said he liked Craig Venter personally, told me, “Having the human genome is like having a Landsat map of the earth, compared to a world where the map tapers off into the unknown with the words ‘There be dragons.’ It’s as different a view of human biology as a map of the earth in the fourteen hundreds was compared to a view from space today.” As for the war between Celera and the Human Genome Project, he said it was silly. “At a certain level, it was just boys behaving badly. It happened to be the most important project in science of our time, and it had all the character of a school-yard brawl.”

  * * *

  ON FEBRUARY 16, 2001, close to three billion letters of the human DNA in their roughly proper order were published by Craig Venter (along with two hundred coauthors) in Science magazine, under the title “The Sequence of the Human Genome.” It was a very good draft of the human genome, but it was not finished or fully accurate. That same week, the Human Genome Project published its own draft of the human genome in Nature. Taken together, these publications represented one of the monumental achievements of the twenty-first century. The implications would be with us for the rest our lives, the rest of our grandchildrens’ lives, and their grandchildrens’ lives. “Humanity has been given a great gift,” declared an editorial in Science. “This stunning achievement has been portrayed—often unfairly—as a competition between two ventures, one public and one private. That characterization detracts from the awesome accomplishment unveiled this week.�
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  Norton Zinder, Watson’s friend, who had feared that he would die before he saw the human genome, said that he felt marvelous. “I made it. Now I’ve gotta stay alive for four more years, or I won’t get all my options in Celera.” Zinder was convinced that Celera’s stock would rise again. (It has not recovered, so far.)

  Norton Zinder was a vigorous-seeming older man. As he spoke, he was sprawled in a chair in his office overlooking the East River, gesturing with both hands raised. He shifted gears and began to look into the future. “This is the beginning of the beginning,” he said. “The human genome alone doesn’t tell you crap. This is like Vesalius. Vesalius did the first human anatomy.” Vesalius published his work in 1543, an anatomy based on his dissections of cadavers. “Before Vesalius,” Zinder went on, “people didn’t even know they had hearts and lungs. With the human genome, we finally know what’s there, but we still have to figure out how it all works. Having the human genome is like having a copy of the Talmud but not knowing how to read Aramaic.”

  * * *

  CRAIG VENTER ended up getting fired from Celera. The man who fired him was Tony L. White, the chief executive of Celera’s parent company (which had been renamed Applera). Tony White had been Craig Venter’s boss during the time Venter worked at Celera—even though Venter was the president of Celera, Applera owned Celera, and so was in control. It seemed that Craig Venter’s business model just wasn’t working out. Venter had figured that Celera would sell information about the human genome to subscribers, who would want to pay money for it. But not enough customers wanted to pay for it.

  The problem for Celera was that the Human Genome Project kept on churning out human DNA code and, with taxpayer money, published an increasingly accurate sequence of the letters in the human DNA—published it all for free on the Internet, available to anybody at no cost. Celera couldn’t compete.