Panic in Level 4: Cannibals, Killer Viruses, and Other Journeys to the Edge of Science (22 page)

In December 1997, executives from Perkin-Elmer began telephoning Craig Venter to see if he’d be interested in running the new company. He blew them off at first, but a few months later he went to California with a colleague, Mark Adams, to check out the prototype Prism. When they saw it, they immediately understood its significance. They were looking at the equivalent of a supersonic jet in relation to a propellor aircraft. Before the end of that day, Venter, Adams, and Hunkapiller had laid out a plan for decoding the human genome
fast.
A month later, Norton Zinder, Watson’s friend, flew to California to see the machine. Zinder saw it, too. “It was just a piece of equipment sitting on a table, but I said, ‘That’s it! We’ve got the genome!’” he recalled. Zinder joined Celera as a member of its board of advisers, and received stock in the company, which considerably enriched him. Now he could take a lesson from Eric Lander; he could cash in on the biotech boom. (“And what’s wrong with that?” he asked me. “The chemists have been cleaning up all their life. Now the biologists are starting to get their hands on the money, and people are saying, ‘Whoo, that’s not kosher!’ What’s not kosher about it?”)

After Norton Zinder got involved financially and scientifically in the Celera effort to race past the Human Genome Project, it led to some strains between him and James Watson. They maintained their friendship but finally had to agree not to speak about Celera with each other. They evidently feared that one or both of them could have a stroke arguing about Craig Venter.

O
NE DAY
not long after Norton Zinder saw the Prism machine and realized it was going to revolutionize the reading of DNA, Craig Venter and Mike Hunkapiller walked into the office of Harold Varmus, the director of the NIH, to talk to him about something. Harold Varmus was a Nobel laureate and an expert in genes and DNA. He had won the Nobel Prize in Medicine in 1989 (with J. Michael Bishop) for a theory of cancer-causing genes—a model of how cancer arises from genes embedded in a person’s code. In Varmus’s office that day, Craig Venter wanted to talk about the human code and the ongoing effort to read it. He announced the pending formation of a corporation, to be led by himself, that was going to decode the human genome. (Celera did not yet have a name.) Venter proposed to Varmus that the company and the public project collaborate, sharing their data and—this point is enormously important to scientists—sharing the publication of the human genome, which meant sharing the credit and the glory for having done the work. This included, of course, the unspoken possibility of the Nobel Prize in Medicine. The Nobel Prize would seem to have been
made
for the team that first decrypted the human DNA.

Harold Varmus was skeptical. He suspected that this wasn’t a sincere offer from Craig Venter. He wondered if Venter might be angling for something that would be good for Craig Venter but maybe not so good for the Human Genome Project. He told Venter that he needed time to consider the proposal, particularly to check back with his subordinate Francis Collins (the head of the NIH’s part of the Human Genome Project), to see what Collins thought of this unusual offer of collaboration.

Later that same day, Craig Venter and Mike Hunkapiller drove to Dulles Airport, where they met Francis Collins at the United Airlines Red Carpet Club. There they personally offered collaboration to Collins.

Venter recalled later that Collins seemed upset with his offer. Collins recalled that he merely asked Venter for some time to consider it. Extra time was one thing that Craig Venter was not prepared to give Francis Collins.

Venter was no stranger to ways of getting attention in the news media. By the time he met with Francis Collins, he had already alerted
The New York Times
to the creation of the new company to sequence human DNA. Just an hour or so after the meeting with Francis Collins he called the
Times
and told the paper it should go ahead and run the story. In the published account, Venter announced that he would sequence the human genome four years ahead of the public project. He would do it, he claimed, for less than a tenth of the projected cost of the public project—that is, he’d do it for less than $200 million, against the $3 billion–plus price tag of the Human Genome Project. The
Times
reporter, Nicholas Wade, implied that the Human Genome Project might not meet its goals and might be superfluous, now that Craig Venter and Celera had come along and were proposing to do the job much faster and much more cheaply—and at zero expense to the taxpayer. Certainly Francis Collins could not have been thrilled when he opened
The New York Times
the next day and read this. He hadn’t yet even given Craig Venter a reply to his offer of collaboration.

By now, there was no stopping Venter. Four days later, on May 12, Venter and Hunkapiller went to the Cold Spring Harbor Laboratory—James Watson’s institute—where a meeting of the heads of the Human Genome Project was taking place. Venter got up and told them, in effect, that they could just give up and stop working, since he was going to sequence the human genome
tout de suite.
Later that week, sitting beside Harold Varmus and Francis Collins at a press conference, Craig Venter looked out at a roomful of reporters and suggested that biology and society would be better off if the Human Genome Project stopped reading human DNA and moved forward to do the genome of…the mouse.

It was a fart in church of magnitude nine. Venter hadn’t really intended to sound so offensive, but he had never been able to keep his mouth under control in a delicate situation. “The mouse is essential for interpreting the human genome,” Venter tried to explain, but that didn’t help.

In the words of one head of a sequencing center who was at the Cold Spring Harbor meeting, “Craig has a certain lack of social skills. He goes into that meeting thinking everyone is going to thank him for doing the human genome himself. The thing blew up into a huge explosion.” The head of another center recalled, “Craig came up to me afterward, and he said, ‘Ha, ha, I’m going to do the human genome. You should go do the mouse.’ I said to him, ‘You bastard. You
bastard,
’ and I almost slugged him.”

They felt that Venter was trying to stake out the human genome for himself as a financial asset while at the same time stealing the scientific credit. They felt that he was belittling their work, telling them to just go do the mouse.

Furthermore, Venter said that he would make the human genome available to the public but would charge customers who wanted to see Celera’s analyzed data, and this made James Watson livid. He did not like the idea of having to pay money to Craig Venter for what he felt was the human heritage, which should be open to all for free. Watson did not deign to attend Venter’s presentation—apparently he stayed up in his blond-paneled office and made telephone calls or fumed—but he appeared in the lobby, where he walked around and, in his strange, drifting voice, said to people, “He’s Hitler. This should not be Munich.” To Francis Collins he said, “Are you going to be Churchill or Chamberlain?”

Venter left the meeting soon afterward. Watson’s remarks got back to him, of course. Venter didn’t appreciate being called the Hitler of the human genome by the discoverer of the structure of DNA. Craig Venter and James Watson seemed to stop speaking with each other after that.

“You have to understand something about Jim Watson,” Watson’s friend Norton Zinder explained to me. “Jim has a kind of verbal Tourette’s syndrome. He shoots his mouth off, and he doesn’t know what he’s saying. He can’t control it.” In this respect, Watson was remarkably like Craig Venter, Zinder pointed out. “Anyway, I wouldn’t want to be Jim Watson,” Zinder remarked.

“Why not?”

“Are you kidding? All he does is fly around the world to meetings, where he accepts another medal for something he did in 1953. It’s a horrible life. I suppose he likes it.”

The British leaders of the public project—John Sulston, the director of the Sanger Centre, and Michael Morgan, of the Wellcome Trust—reacted swiftly to Craig Venter’s announcement. They were in England, but they flew to the United States and the next day arrived at Cold Spring Harbor, where they found things in disarray, if not total fibrillation, over Venter’s announcement, with scientists wondering if the Human Genome Project was going to die. To a standing ovation, Michael Morgan got up and played the role of Winston Churchill. He read a statement declaring that the Wellcome Trust would nearly double its funding for the public project, and would challenge any “opportunistic” patents of the genome. “We were reacting, in part, to Craig’s suggestion that we just close up shop and go home,” Morgan later explained to me.

Venter also announced that Celera would use the whole-genome shotgun method—once again, as with his EST method, he was pushing the envelope of the possible, reaching for a new but seemingly risky technique to speed up the work of decoding the letters of DNA. The public project had chosen a more conventional method. John Sulston and Robert Waterston, the head of the sequencing center at Washington University, published a letter in
Science
asserting that Venter’s method would be “woefully inadequate.” Francis Collins was quoted in
USA Today
as saying that Celera was going to produce “the Cliffs Notes or the Mad Magazine version” of the human genome. (Collins later said that his words had been taken out of context by the reporter, and that he regretted the quote.) Norton Zinder, Watson’s friend, told me that he wasn’t at all surprised that Celera was getting ready to cream the government and decode the human DNA first. “The government will never be able to move as fast as a company,” he said. “Anyway, it’s an industrial job! That’s why Celera is beating the crap out of the government.”

T
HE COMPANY
forged from Perkin-Elmer amid the turmoil was the PE Corporation, which was divided into two pieces, the PE Biosystems Group, the unit that was making the Prism machines, and Celera Genomics, which was using the machines to decode the human DNA. Michael Hunkapiller, who became the president of PE Biosystems, believed that he could sell a lot of machines to everyone, including to the Human Genome Project. Craig Venter’s project would demonstrate how effective the Prism machines were; it was advertising. The deal was that there was a fat profit margin in the chemicals the machines used. The chemicals had a much higher profit margin than the machine; not only that, but the chemicals actually cost far more than the machine over the machine’s lifetime. This was the razor-blade principle: if you put inexpensive razors in people’s hands, you will make money selling blades.

James Watson quietly went to some key members of Congress and persuaded them to spend more money on the public project. At the same time, the leaders of the project announced a radical new game plan: they would produce a “working draft” of the human genome a year
ahead
of when Venter said he’d be done. An epic race had begun.

Michael Morgan, of the Wellcome Trust, told me what he thought had happened with the creation of Celera. “From the first press release, Craig saw the public program as something he wanted to denigrate,” Morgan said. “This was our first sign that Celera was setting out to undermine the international effort. What is it that motivates Craig? I think he’s motivated by the same things that drive other scientists—personal ego, a degree of altruism, a desire to push human knowledge forward—but there must be something else that drives the guy. I think Craig has a huge chip on his shoulder that makes him want to be loved. I actually think Craig is desperate to win a Nobel Prize. He also wants to be very, very rich. There is a fundamental incompatibility there.”

One day, I ran into a young player in the Human Genome Project. He believed in the worth and importance of the public project and said that he had turned down a job offer from Celera. He didn’t have any illusions about human nature, or about any of the major players. He said, “Here’s why everyone is so pissed at Craig. The whole project started when James Watson persuaded Congress to give him money for the human genome, and he turned around and gave it to his friends—they’re the heads of centers today. It grew into a lot of money, and then the question was, Who was going to get the Nobel Prize? In the United States, there were seventeen centers in the project, and there was no quality control. It didn’t matter how bad your data was, you just had to produce it, and people weren’t being held accountable for the quality of their product. Then Celera appeared. Because of Celera, the NIH was suddenly forced to consolidate its funding. The NIH and Francis Collins began to dump more than eighty percent of the money into just three centers—Baylor, Washington University, and MIT—and they jacked everybody else. They had to do it, because they had to race Celera, and they couldn’t control too many players. So all but three centers were cut drastically, and some of the labs closed down. Celera was not just threatening their funding but threatening their very lives and everything they had spent years building. It’s kind of sad. Now those people hang around meetings, and the leaders treat them like ‘If you’re really nice, we’ll give you a little piece of the mouse genome.’ That’s the reason so many of them are so angry at Celera. It’s easier for them to go after Craig than to go after Francis Collins and the NIH.”

A
T
C
ELERA’S HEADQUARTERS
in Rockville, I was shown how human DNA was shotgunned into small pieces when it was sprayed through a hospital nebulizer that cost a dollar fifty. The DNA fragments were then introduced into E. coli bacteria and grown in glass dishes. The bacteria formed brown spots—clones—on the dishes. Each spot had a different fragment of human DNA growing in it. The dishes were carried to a room where three robots sat in glass chambers the size of small bedrooms. Each robot had an arm that moved back and forth rapidly over a dish. Little needles on the arms kept stabbing down and taking up the brown spots. Later, the bits of human DNA in the bacteria would be separated from the bacteria and run through the sequencing machines, producing little bits of human DNA code.