Panic in Level 4

The Human Kabbalah

“CRAIG VENTER IS AN ASS. He’s an idiot. He is a thorn in people’s sides and an egomaniac,” a senior scientist in the Human Genome Project said to me one day. The Human Genome Project was an ongoing nonprofit international research consortium that had been working to decipher the complete sequence of nucleotides, or letters, in human DNA. The human genome is the total amount of DNA that is spooled into a set of twenty-three chromosomes in the nucleus of every typical human cell. (There are two sets of chromosomes, for a total of forty-six chromosomes in each human cell.) This entire package of DNA in every cell is sometimes referred to as the book of human life. Most scientists agreed that deciphering it would be one of the great achievements of our time. The stakes, in money and glory, to say nothing of the future of medicine, were huge and incalculable.

In the United States, most of the money to pay for the Human Genome Project had been coming from the National Institutes of Health, the NIH. The project was often referred to, in a kind of shorthand, as the “public project,” to distinguish it from for-profit enterprises like the Celera Genomics Group, of which Craig Venter was the president and chief scientific officer. “In my perception,” said the scientist who was giving me the dour view of Venter, “Craig has a personal vendetta against the National Institutes of Health. I look at Craig as being an extremely shallow person who is only interested in Craig Venter and in making money. Only God knows what those people at Celera are doing.”

What Venter and his colleagues were doing was preparing to announce that they had placed in the proper order something like 95 percent of the readable letters in the human genetic code. They were referring to this milestone as the first assembly. They had already started selling information about the human genome to subscribers. The Human Genome Project, largely in response to Craig Venter and the corporate effort to read the human book of life, was also on the verge of announcing a milestone. Its scientists were calling their milestone a “working draft” of the genome. They were claiming it was more than 90 percent complete, and they were making the information available to anyone, free of charge, on a database called GenBank. Both images of the human genome—Celera’s and the public project’s—were becoming clearer and clearer. The book of life and death was opening, and we held it in our hands.

A HUMAN DNA MOLECULE is about a meter long. It is about a twenty-millionth of a meter wide—the width of twenty hydrogen atoms. It is shaped like a twisted ladder. Each rung of the ladder is made of one of four nucleotides—adenine, thymine, cytosine, and guanine. The DNA code is expressed in combinations of the letters A, T, C, and G, the first letters of the names of the nucleotides. The human genome contains at least 3.2 billion letters of genetic code. This is about the number of letters in three thousand copies of Moby-Dick.

Perhaps three percent of the human code consists of genes. Genes hold the recipes for making proteins. Human genes are stretches of between a thousand and fifteen hundred letters of code, often broken into pieces and separated by long passages of DNA that don’t code for proteins. It is believed that there are about twenty-five thousand genes in the human genome. Much of the rest of the genome consists of blocks of seemingly meaningless letters, gobbledygook. These sections are referred to as junk DNA, although it may be that we just don’t understand the function of the apparent junk.

The conventional route for announcing scientific breakthroughs is publication in a scientific journal. Both Celera and the Human Genome Project were planning to publish annotated versions of the human genome as soon as possible. Although the two sides looked like armies maneuvering for advantage, the leaders of the Human Genome Project had always denied that they were involved in some kind of competition with Craig Venter.

“They’re trying to say it’s not a race, right?” Venter said to me, in a shrugging sort of way. “But if two sailboats are sailing near each other, then by definition it’s a race. If one boat wins, then the winner says, ‘We smoked them,’ and the loser says, ‘Eh, we weren’t racing—we were just cruising.’”

I first met Craig Venter on a windy day in the summer of 1999, at Celera’s headquarters in Rockville, Maryland, a half-hour drive northwest of Washington, D.C. The company’s offices and laboratories occupied a pair of five-story white buildings with mirrored windows, surrounded by beautiful groves of red oaks and yellow poplar trees. One of the buildings contained rooms packed with row after row of DNA-sequencing machines of a type known as the ABI Prism. The other building held what was said to be the most powerful civilian computer array in the world. The Celera supercomputer complex was of considerable interest to Gregory and David Chudnovsky, the mathematicians who had used a homemade supercomputer to calculate the number pi, and who ended up meeting with Craig Venter and his staff, talking with them about the design of supercomputers and software used in sequencing the human genome. Venter’s supercomputer complex was surpassed only, perhaps, by that of the Los Alamos National Laboratory, which is used for simulating nuclear bomb explosions.

The computer building at Celera also contained the Command Center. This was a room stuffed with control consoles and computer screens. The Command Center was manned all the time. It monitored the flow of DNA inside Celera. The DNA was flowing through the machines twenty-four hours a day, seven days a week.

That hot summer day, Craig Venter moved restlessly around his office. There had been a spate of newspaper stories about the race to decode the complete genome, and about the pressure Celera was putting on its competitors. “We’re scaring the crap out of everybody, including ourselves,” he said to me.

Venter was fifty-three at the time. He had an active, cherubic face on which a smile often flickered. He was bald, with a fuzz of short hair at the temples, and his head was usually sunburned. He had bright blue eyes and a soft voice. That day, he was wearing khaki slacks and a blue shirt, New Balance running shoes, a preppy tie with small turtles on it, and a Rolex watch. Venter’s office looked out into stands of trees; leaves were spinning on branches outside the windows, flashing their white undersides and promising thunderstorms. Beyond the trees, a chronic traffic jam was occurring on the Rockville Pike. Celera was in an area along a stretch of Interstate 270 known as the biotechnology corridor, which was dense with companies specializing in the life sciences, and billions of dollars in venture capital were embedded in bioenterprises all around Celera.

Celera Genomics was a part of the PE Corporation, which had been called Perkin-Elmer before the company’s chief executive, Tony L. White, split the business into two parts: PE Biosystems, now called Applera, which made the DNA sequencing machine called the Prism, and Celera. Venter owned five percent of Celera’s stock. It had been trading, often violently, on the New York Stock Exchange. The stock had been tossed by waves of panic selling and panic buying. That particular summer day, the stock market was valuing Celera at around three billion dollars. Craig Venter’s own net worth had been slopping around by five or ten million dollars a day in either direction, like water going back and forth in a bathtub.

“Our fundamental business model is like Bloomberg’s,” Venter said. “We’re selling information about the vast universe of molecular medicine.” Venter hoped, for example, that one day Celera would help analyze the genomes of millions of people as a regular part of its business. This would be done over the Internet, he felt—and, having decoded individual patients’ DNA, the company would then help design or select drugs tailored to patients’ particular needs. In recent times, genomics has been moving so fast that it’s possible to think that pretty soon you will be able to walk into a doctor’s office and have your own genome read and interpreted. It could be stored in a smart card. (You would want to keep the card in your wallet, in case you landed in an emergency room. But you wouldn’t want to lose it, because if thieves got your DNA sequence, they might really be able to clone you.) Your doctor would read the smart card, and it would show your total biological-software code. Your doctor would be able to see the bugs in your code. The bugs are genes that make you vulnerable to certain diseases; everyone has bugs in their code. If you became sick, doctors could watch the activity of your genes, using so-called gene chips, which are small pieces of glass containing detectors for every gene. Doctors could track how your body responded to treatment. All your genes could be observed, operating in an immense symphony.

Venter stopped moving briefly, sat down in front of a screen, and tapped a keyboard. A Yahoo! quote came up. “Hey, we’re over twenty today,” he said. Meanwhile, I was standing in front of a large model of Venter’s yacht, the Sorcerer, in which he’d won the 1997 Transatlantic Challenge in an upset victory—it was the only major ocean race he’d ever entered. “I got the boat for a bargain from the guy who founded Lands’ End,” Venter said. “I like to buy cast-off things on the cheap from ultrarich people.”

Venter went into the hallway, and I followed him. Celera was renovating its space, and tiles were hanging from the ceiling. Some had fallen to the floor. Black stains dripped out of air-conditioning vents, and sheets of plywood were lying around. Workmen were Sheetrocking walls, ripping up carpet, and installing light fixtures, and the smell of paint and spackle drifted in the air. We took the stairs to the basement and entered a room that held about fifty Prism DNA-sequencing machines. Each Prism was the size of a small refrigerator and had cost three hundred thousand dollars. Prisms were the fastest DNA sequencers on earth. At the moment, they were reading the DNA of the fruit fly. This was a pilot project for the human genome. The machines contained lasers, which were used for reading the letters in DNA. Heat from the lasers seemed to ripple from the machines. The lasers were shining light on tiny tubes through which strands of fruit-fly DNA were moving, and the light was passing through the DNA, and sensors were reading the letters of the code. Each machine had a computer screen on which blocks of numbers and letters were scrolling past. It was fly code.

“You’re looking at the third-largest DNA-sequencing facility in the world,” Venter said. “We also have the second largest and the largest.”

We got into an elevator. The walls of the elevator were dented and bashed. Venter led me into a vast, low-ceilinged room that looked out into the trees. This was the largest DNA-decoding factory on earth. The room contained 150 Prisms—forty-five million dollars’ worth—and more Prisms were due to be installed any day. Just below the ceiling, air ducts dangled on straps, and one wall consisted of gypsum board.

Venter moved restlessly through the unfinished space. “This is the most futuristic manufacturing plant on the planet right now,” he said. Outdoors, the rain came, splattering on the windows, and the poplar leaves shivered. We stopped and looked over a sea of machines. “You’re seeing Henry Ford’s first assembly plant,” he said. “What don’t you see? People, right? There are three people working in this room. A year ago, this work would have taken one thousand to two thousand scientists. With this technology, we are literally coming out of the dark ages of biology. As a civilization, we know far less than one percent of what will be known about biology, human physiology, and medicine. My view of biology is ‘We don’t know squat.’”

Some observers thought the company could fail. It was burning through at least $150 million a year. This flow of money going out of Celera was what venture capitalists called the “burn rate” of a start-up company—its negative cash flow, its consumption of money without (yet) producing a cash return on the investment. Who, I wondered, would want to buy the information the company was generating, and how much would they pay for it? “There will be an incredible demand for genomic information,” Venter assured me. “When the first electric-power companies strung up wires on power poles, there were a lot of skeptics. They said, ‘Who’s going to buy all that electricity?’ We already have more than a hundred million dollars in committed subscription revenues over five years from companies that are buying genomic information from us—Amgen, Novartis, Pharmacia & Upjohn, and others. After we finish the human genome, we could do the mouse, rice, rat, dog, cow, corn, maybe apple trees, maybe clover. We could do the chimpanzee.”

ONE DAY AT CELERA’S HEADQUARTERS, I was talking with a molecular biologist named Hamilton O. Smith. Smith, an extremely distinguished figure in the history of molecular biology, won a Nobel Prize in 1978 as a codiscoverer of restriction enzymes, which are used to cut DNA in specific places. Scientists use these enzymes like scissors, chopping up pieces of DNA so that they can be studied or recombined with other pieces of DNA. Without the DNA-cutting scissors that Hamilton Smith discovered, there would be no such thing as genetic engineering or molecular biology. Most people in his field who knew him called him Ham Smith.

Ham Smith was in his late sixties. He stood six feet five inches tall. He had a shock of stiff white hair and a modest manner. Working for Celera, he seemed to be a putterer, knocking around in a sophisticated lab while helping the company decode the human genome.

“Have you ever seen human DNA?” Ham Smith asked me, as he poked around his lab.

“No.”

“It’s beautiful stuff.”

He brought me over to a small box that sat on a countertop. It held four small plastic tubes, each the size of a pencil stub. “These four tubes hold enough human DNA to do the entire human genome project,” Smith said. “There’s a couple of drops of liquid in each tube.”

He lifted up one of the tubes and turned it over in the light to show me what DNA looks like to the naked eye. A droplet of clear liquid moved back and forth in the tube. It was the size of a dewdrop. Then he held up a glass vial and rocked it back and forth; a crystal-clear, syrupy liquid oozed around in it. “That’s long, unbroken DNA,” Hamilton Smith said. He’d extracted it from human blood—from white blood cells. “This liquid looks glassy and clear, but it’s snotty,” he went on. “It’s like sugar syrup. It really is a sugar syrup, because there are sugars in the backbone of the DNA molecule. Watch this.”

Smith picked up a pipette, a handheld device with a hollow plastic needle in it, used for moving tiny quantities of liquid from one place to another. His hands were large, but they moved with precision. Holding the pipette, he sucked up a droplet of DNA mixed with a type of purified salt water called buffer. He held the drop in the pipette for a moment, then let it go. The droplet drooled. It reminded me of a spider dropping down a silk thread.

“There the DNA goes, it’s stringing,” he said. “The pure stuff is gorgeous.”

The molecules were sliding along one another, like cooked spaghetti falling out of a pot, causing the water to string out. “It’s absolutely glassy clear, without color,” he went on. “Sometimes it pulls back into the tube and won’t come out. I guess that’s like snot, too, and then you have to almost cut it with scissors. The molecule is actually quite stiff. It’s stiff like a plumber’s snake. It bends, but only so much, and then it breaks. It’s brittle. You can break it just by stirring it.”

The samples of DNA that Celera was using were kept in a freezer near Smith’s office. When he wanted to get some human DNA, he removed a vial of frozen white blood cells or sperm from the freezer. The vials had coded labels. He would thaw the sample of cells or sperm, then mix the material with salt water, along with a little bit of detergent. A typical human cell looks like a fried egg, and the nucleus of the cell resembles the yolk. The detergent mixes the whites and the yolks—rather like scrambling an egg. As the cell falls apart, strands of DNA spill out in the salt water. The debris, the broken bits of the cell, fall to the bottom of the vial, leaving tangles of DNA suspended in the liquid.

One of Smith’s research associates, a woman named Cindi Pfannkoch, showed me what shattered DNA was like. Using a pipette, she drew a tiny amount of liquid from a tube and let a drop fall to a sheet of wax, where it beaded up like a tiny jewel, the size of the dot over this i. An ant could have drunk it in full.

“There are two hundred million fragments of human DNA in this drop,” she said. “We call that a DNA library.”

She opened a plastic bottle, revealing a white fluff. “Here’s some dried DNA.” She took up a pair of tweezers and dragged out some of the fluff. It was a wad of dried DNA from the thymus gland of a calf. The wad was about the size of a cotton ball, and it contained several million miles of DNA.

“In theory,” Ham Smith said, “you could rebuild the entire calf from any bit of that fluff.”

I placed some of the DNA on the ends of my fingers and rubbed them together. The stuff was sticky. It began to dissolve on my skin. “It’s melting—like cotton candy,” I said.

“Sure. That’s the sugar in DNA,” Smith said.

“Would it taste sweet?”

“No. DNA is an acid, and it’s got salts in it. Actually, I’ve never tasted it.”

Later, I got some dried calf DNA. I placed a bit of the fluff on my tongue. It melted into a gluey ooze that stuck to the roof of my mouth in a blob. The blob felt slippery on my tongue, and the taste of pure DNA appeared. It had a soft taste, unsweet, rather bland, with a touch of acid and a hint of salt. Perhaps like the earth’s primordial sea. It faded away.

The DNA came from five anonymous donors who had contributed their blood or semen for use in Celera’s human genome project. The donors included both men and women, and a variety of ethnic groups. “I wouldn’t be surprised if one of the donors is Craig,” Ham Smith remarked.

CRAIG VENTER grew up in a working-class neighborhood on the east side of Millbrae, on the San Francisco peninsula. “My father was a CPA all his life, and my mother was very much a Donna Reed kind of mother,” he said. “We were middle-class at a time when being middle-class really meant you had no money. It was a very big deal when my dad’s income went past twelve thousand dollars a year. He was a Mormon who had been excommunicated for smoking and drinking coffee, and he was proud of it. His single strongest character trait was absolute honesty to a fault.” Venter’s father died at age fifty-nine of a heart attack.

They lived near the railroad tracks. One of his favorite childhood activities, he said, was to play chicken on the tracks. He and his friends would stand on the tracks when a locomotive was coming, and the last kid to jump out of the way was the winner. In high school, his grades mostly stank, but he excelled in science and shop. He also became a champion swimmer and broke his league’s records in the backstroke. “I was essentially grounded throughout high school—I was always in trouble,” he said. “I was disinclined to take tests.” He got F’s by default. His favorite high school teacher was Gordon Lish, who later became a distinguished novelist and editor. “Gordon Lish got fired from my high school for supposedly un-American activities,” Venter said. “He slouched during the Pledge of Allegiance—he couldn’t or wouldn’t stand up straight. When he was fired for this, I led a demonstration that turned into a riot, and we shut down the school. The principal called me into his office and said, ‘You must be getting extraordinary grades from this Lish.’ I said, ‘No, I’m getting F’s, but I deserve them.’”

During his senior year of high school, Craig Venter spent a lot of time surfing in Half Moon Bay. After high school, he attended two junior colleges in a desultory way, but mostly he surfed. At that time, Venter had long blond hair and a beautiful body. Then he got a draft notice. He quickly enlisted in the Navy to avoid having to serve in the Army. (“My parents had both been in the Marine Corps, and they looked at the Army as the lowest form of life.”) He ended up getting trained as a medical corpsman. He worked at the Navy hospital in San Diego, and ended up running a tuberculosis ward. He developed a passion for medicine. “Things clicked in for me, all of a sudden. I got hungry for knowledge,” he said. He served as a medical corpsman in Vietnam, and twice he was sentenced to the brig for disobeying orders.

Venter had a history of confrontation with government authorities. As an enlisted man in San Diego, he was court-martialed for refusing a direct order given by an officer. “She happened to be a woman I was dating,” Venter said. “We had a spat, and she ordered me to cut my hair. I refused.” A friend of Venter’s, Ron Nadel, who was a doctor in Vietnam, recalled that one of Venter’s blowups with authority involved “telling a superior officer to do something that was anatomically impossible.” Venter worked for a year in the intensive care ward at Da Nang hospital, where, he calculated, more than a thousand Vietnamese and American soldiers died during his shifts, many of them while the 1968 Tet Offensive was raging, the North Vietnamese and the Vietcong launching bloody attacks on American positions across South Vietnam. “That was when I learned that our government lies,” Venter said. “I can’t say how many thousands of cases and how many deaths occurred in the Da Nang hospital during the Tet Offensive. And I’d get letters back from friends in the United States saying that the newspapers were saying it wasn’t that bad, there were only a few hundred casualties. The government was lying. I turned twenty-one in Vietnam.” When he returned to the United States, Venter finished college, then earned a PhD in physiology and pharmacology from the University of California at San Diego. His discovery, in Vietnam, that the government lied seemed to be at the center of his relationship with the rival Human Genome Project. They were the government: they lied.

Venter got married to a molecular biologist, Claire Fraser, who was the president of The Institute for Genomic Research (TIGR, pronounced “Tiger”), in Rockville, a nonprofit institute that he and Fraser had helped establish in 1992. In 1998, he endowed TIGR with half of his original stake in Celera—five percent of the company. The money would be used to analyze the genomes of microbes that cause malaria and cholera and other diseases. (Venter and Fraser divorced in 2004.)

A few years ago, Venter developed a hole in his intestine, due to diverticulitis. He collapsed after giving a speech, and nearly died. He recovered, but he blamed the stress caused by his enemies for his burst intestine. Venter had enemies of the first order. They were brilliant, famous, articulate, and regularly angry at him. At times, Venter seemed to thrive on his enemies’ indignation with an indifferent grace, like a surfer shooting a tubular wave, letting himself be propelled through their cresting wrath. At other times, he seemed baffled, and said he couldn’t understand why they didn’t like him.

One of Venter’s most distinguished enemies, at the time, was James D. Watson, who, with Francis Crick and Maurice Wilkins, had won the Nobel Prize for discovering the shape of the DNA molecule—what they called the double helix. They did this work in 1953, and it changed forever the direction of biology. Their discovery showed that all the processes of life were encoded in a molecule, which, in theory, could be decoded—read like a book. James Watson helped found the Human Genome Project, and he was the first head of the NIH genome program. I visited him one day in his office at the Cold Spring Harbor Laboratory, on Long Island; he was the president of the laboratory. His office was paneled in blond oak, with a magnificent eastward view across Cold Spring Harbor. Watson was then in his seventies. He had a narrow face, lopsided teeth, a frizz of white hair, sharp, restless eyes, a squint, and a dreamy way of speaking in sentences that trailed off. He put his hands on his head and squinted at me. “In 1953, with our first paper on DNA, we never saw the possibility…” he said. He looked away, up at the walls, and didn’t finish the sentence. “No chemist at the time ever thought we could read the molecule,” he went on. But he, along with a number of biologists, began to think that reading the human DNA might just be possible. If the human book of life could be read, then the causes of many human diseases could be found and understood, and could be cured.

By the mid-1980s James Watson had become convinced that the decryption of the genome was an important goal and should be pursued, even if it cost billions and took decades. Part of his motivation might have been personal. James Watson had many eccentricities. He had a son who also seemed eccentric and, according to Watson, was not able to fully take care of himself. James Watson loved his son, and in witnessing his son’s problems, it would be understandable that he ached to decode the human DNA in order to alleviate human suffering.

Watson appeared before Congress in May 1987 and asked for an initial annual budget of thirty million dollars for the project. The original plan was to sequence the human genome by 2005, at a projected cost of about three billion dollars. The principal work of the project was carried out by five major DNA-sequencing centers, as well as by a number of smaller centers around the world—all academic, nonprofit labs. The big centers included one at Baylor University, in Texas; one at Washington University, in St. Louis; the Whitehead Institute at MIT; the Joint Genome Institute of the Department of Energy; and the Sanger Centre, near Cambridge, England. The Wellcome Trust of Great Britain—the largest nonprofit medical research foundation in the world—funded the Sanger work, which was to sequence a third of the human genome. One of the founding principles of the Human Genome Project was the immediate release of all the human code that was found, making it available free of charge and without any restrictions on who could use it or what anyone could do with it.

In 1984, Craig Venter had begun working at the NIH, where he eventually developed an unorthodox strategy for decoding bits of genes. At the time, other scientists were painstakingly reading the complete sequence of each gene they studied. This process seemed frustratingly slow to Venter. He began isolating what are called expressed sequence tags, or ESTs, which are fragments of DNA at the ends of genes. When the ESTs were isolated, they could be used to identify genes in a rough way. With the help of a few sequencing machines, Venter identified bits of thousands of human genes. This was a source of unease at the NIH, because it was a kind of skimming rather than a complete reading of genes. Venter published his method in 1991 in an article in Science, along with partial sequences from about 350 human genes. The method was not received well by many genomic scientists. It was fast, easy, and powerful, but it didn’t look elegant; it looked like an application of brute force, and some scientists seemed threatened by it. Venter claimed that two of his colleagues, who eventually became heads of public genome centers, had asked him not to publish his method or move forward with it for fear they would lose their funding for genome sequencing done their way.

The NIH decided to apply for patents on the gene fragments Venter had identified. James Watson blew his stack over the idea of anyone trying to patent bits of genes. He got into a hostile situation with the director of the NIH, Bernadine Healy, who defended the patenting effort. In July 1991, during a meeting in Washington called by Senator Pete Domenici, of New Mexico, to review the genome program, Watson disparaged Craig Venter’s methods. “It isn’t science,” he said, adding that Venter’s machines “could be run by monkeys.”

It was a strange moment. The Senate hearing room was almost empty—few politicians were interested in genes then. But Craig Venter was sitting in the room. “Jim Watson was clearly referring to Craig as a monkey in front of a U.S. senator,” another scientist who was there said to me. “He portrayed Craig as the village idiot of genomics.” Venter seemed to almost thrash in his chair, stung by Watson’s words. “Watson was the ideal father figure of genomics,” Venter says. “And he was attacking me in the Senate, when I was relatively young and new in the field.”

That day in his office in Cold Spring Harbor, James Watson insisted to me that he hadn’t been comparing Craig Venter to a monkey. “It’s the patenting of genes I was objecting to. That’s why I used the word ‘monkey’! I hate it!” he said testily. The patent office turned down the NIH’s application for a patent, anyway. But a few years later, two genomics companies, Incyte and Human Genome Sciences, adopted Craig Venter’s EST method for finding genes, and it became the foundation of their businesses. Those businesses, combined, were worth many billions of dollars on the stock market. Samuel Broder, the chief medical officer at Celera, who was a former director of the National Cancer Institute, said to me, heatedly, “None of the people who severely and acrimoniously criticized Craig for his EST method ever said they were personally sorry. They ostracized Craig and then went on to use his method with never an acknowledgment.”

James Watson said, “The EST method has proved immensely useful, and it should have been encouraged.”

Venter was increasingly unhappy at the NIH. He had received a ten million dollar grant to sequence human DNA, and he asked for permission to use some of the money to do EST sequencing, but his request was denied by the Human Genome Project (which James Watson was then running). Venter returned the grant money with what he says was a scathing letter to Watson. In addition, Venter’s wife, Claire Fraser, had been denied tenure at the NIH. Her review committee (which was composed entirely of middle-aged men, she said) explained to her that it could not evaluate her work independently of her husband’s. At the time, Fraser and Venter had separate labs and separate research programs. Fraser considered suing the NIH for sex discrimination.

Meanwhile, James Watson, as head of the Human Genome Project at the NIH, had gotten himself into continuing scrapes with the head of the NIH, Bernadine Healy. During a press conference at which Healy was present, Watson criticized the NIH’s policy of seeking patents on genes, and he labeled Healy (who was his boss) a “lunatic.” Shortly afterward, Bernadine Healy fired James Watson. She forced him to resign from his position as head of the Human Genome Project. Watson had done himself in with his mouth.

That summer, Craig Venter was approached by a venture capitalist named Wallace (Wally) Steinberg, who wanted to set up a company that would use Venter’s EST method to discover genes, create new drugs, and make money. “I didn’t want to run a company, I wanted to keep doing basic research,” Venter said. But Wally Steinberg offered Venter a research budget of seventy million dollars over ten years—a huge amount of money, then, for biotech. Venter, along with Claire Fraser and a number of colleagues, left the NIH and founded TIGR, which is a nonprofit organization. At the same time, Wally Steinberg established a for-profit company, Human Genome Sciences, to exploit and commercialize the work of TIGR, which was required to license its discoveries exclusively to its sister company. Thus Venter got millions of dollars for research, but he had to hand his discoveries over to Human Genome Sciences for commercial development. Venter had one foot in the world of pure science and one foot in a bucket of money.

By 1994, the Human Genome Project was mapping the genomes of model organisms, which included the fruit fly, the roundworm, yeast, and E. coli (a bacteria that lives in the human gut), but no genome of any organism had been completed, except for virus genomes, which are relatively small. Venter and Hamilton Smith (the Nobel laureate and discoverer of DNA “scissor” enzymes, who was then at the Johns Hopkins School of Medicine) proposed speeding things up by using a technique known as whole-genome shotgun sequencing. In shotgunning, the genome is broken into small, random, overlapping pieces, and each piece is sequenced, or read. Then the jumble of pieces is reassembled in a computer that compares each piece to every other piece and matches the overlaps, thus assembling the whole genome. It’s quite a lot like putting together a picture puzzle by matching the edges of the pieces to neighboring pieces, except that a genome can consist of millions of pieces and the task of matching them up to form a whole image of a genome requires superpowerful computers and really hot software.

Venter and Smith applied for a grant from the NIH to shotgun-sequence the genome of a disease-causing bacterium called Haemophilus influenzae, or H. flu for short. It causes fatal meningitis in children. They proposed to do it in just a year. H. flu has 1.8 million letters of code, which seemed massive then (though the human code is two thousand times as long). The review panel at the NIH gave Venter’s proposal a low score, essentially rejecting it. According to Venter, the panel claimed that an attempt to shotgun-sequence a whole microbe was excessively risky and perhaps impossible. He appealed. The appeals process dragged on. While the appeals dragged on, he went about shotgunning H. flu anyway. Venter and the TIGR team had nearly finished sequencing the H. flu genome when, in early 1995, a letter arrived at TIGR saying that the appeals committee had denied the grant on the ground that the experiment wasn’t feasible. Venter published the H. flu genome a few months later in Science. Whole-genome shotgunning had worked in spite of the objections of a funding committee at the NIH; it was almost as if the NIH wanted to prevent Venter’s method from working. The method worked very well, however; this was the first completed genome of a free-living organism.

It seems quite possible that Venter’s grant was denied because of politics. The NIH, the National Institutes of Health, is funded by tax dollars. The review panel seems to have hated the idea of giving taxpayer money to TIGR to make discoveries that would be turned over to a corporation, Human Genome Sciences, which could then profit from the discoveries. It turned down the grant in spite of the fact that “all the smart people knew the method was straightforward and would work,” said Eric Lander, one of the leaders of the Human Genome Project.

Around this time, the venture capitalist Wally Steinberg died of a heart attack, and his death provided a catalyst for a split between TIGR and Human Genome Sciences, which was run by a former AIDS researcher, William Haseltine. Venter and Haseltine were widely known to despise each other. Venter had already sold his stock in Human Genome Sciences because of the rift between them, and after Steinberg died the relationship between the two organizations was formally ended.

Late in 1997, TIGR was doing some DNA sequencing for the Human Genome Project, and Venter began going to some of the project’s meetings. That was when he started calling the heads of the public project’s DNA-sequencing centers the Liars’ Club, claiming that their predictions about when they would finish a task and how much it would cost were lies. His calling them liars did not win him many friends.

Francis Collins, a distinguished medical geneticist from the University of Michigan, had become the head of the NIH genome program shortly after James Watson resigned in 1992. In early January 1998, an internal budget projection from Collins’s office somehow made its way to Watson (he seemed able to find out anything that was happening anywhere in molecular biology). This budget projection was supposed to be secret. It was an “eyes only” document intended to be seen by only about eight people, namely the top heads of the Human Genome Project. It contained a graph marked “Confidential” indicating that Francis Collins planned to spend only sixty million dollars per year on direct human-DNA sequencing through 2005. This was peanuts. It also predicted that by that year—when the human genome was supposed to be completed—actually only 1.6 billion to 1.9 billion letters of human code would be sequenced; that is, slightly more than half of the human genome would be done by then. The implication was that the whole human genome wouldn’t get done until maybe 2008 or afterward.

This upset James Watson. Watson had hoped that his successor, Francis Collins, would aggressively pursue the human genome and get the work done as fast as possible; for one thing, he, James Watson, wanted to be alive to see the human genome. Second, the millions of people around the world who suffered from genetic diseases weren’t getting any younger. He decided to discuss it with Eric Lander, the head of the Human Genome Project’s DNA-sequencing center at MIT. Lander was a voluble, articulate, brilliant man in his forties who projected a high degree of self-confidence. He spoke in a rapid voice. He had a broad face and a mustache, and he owned stock in biotech companies that he advised or had helped to found. Eric Lander had become quite wealthy.

On January 17, James Watson traveled to Rockefeller University, on the East Side of Manhattan, where Eric Lander was giving the prestigious Harvey Lecture. The two men met after the lecture at the faculty club at Rockefeller. They were dressed in tuxedos, and Eric Lander had been drinking. By long tradition among medical people, the Harvey Lecture is given and listened to under the influence. Watson himself seemed a little tipsy. The scientists continued to drink after the lecture.

The Rockefeller faculty club overlooks a lawn and sycamore trees and the traffic of York Avenue. Watson and Lander sat down with cognacs at a small table in a dim corner of the room, on the far side of a pool table, where they could talk without being overheard. Also present and drinking cognac was a biologist named Norton Zinder, who was one of Watson’s best friends. Zinder, like Watson, was a founder of the Human Genome Project. One of the older men brought up the confidential budget document with Lander, and both of them began to press him about it. They felt that it provided evidence that Francis Collins did not intend to spend more than sixty million dollars a year on human-DNA sequencing—and this was nowhere near enough money to get the job done anytime soon, they felt.

Watson evidently believed that Eric Lander had influence with Francis Collins, and he urged him to try to persuade Collins to spend more on direct sequencing of human DNA, and to twist Congress’s arm for more money.

Norton Zinder was somewhat impaired with cocktails. “This thing is potchkying along, going nowhere!” he said, hammering the little table and waving his arms as he spoke. For him, the issue was simple: he had had a quadruple coronary bypass, and he had been receiving treatments for cancer, and now he was afraid he would not live to see the deciphering of the human genome. The human genome had begun to seem like a vision of Canaan to Norton Zinder, and he thought he wouldn’t make it there.

Eric Lander did not view things the way the older biologists did. In his opinion, the problem was organizational. The Human Genome Project was “too bloody complicated, with too many groups.” He felt the real problem was a lack of focus. He wanted the project to create a small, elite group that would do the major sequencing of human DNA—shock cavalry that would lead a charge into the human genome.

The three men downed their cognacs with a gloomy sense of frustration. “I had essentially given up on seeing the human genome in my lifetime,” Zinder said.

NOT LONG BEFORE Watson and his friends began lamenting the slowness of the public project, the Perkin-Elmer Corporation, which was a manufacturer of lab instruments, had started secretly talking about an ambitious corporate reorganization. It controlled more than 90 percent of the market for DNA-sequencing equipment, and it was developing the Prism machine. The Prism was then only a prototype sitting in pieces in a laboratory in Foster City, California, but already it looked as if it was going to be at least ten times faster than any other DNA-sequencing machine. Perkin-Elmer executives began to wonder just what it could do. One day Michael Hunkapiller, who was then the head of the company’s instrument division, got out a pocket calculator and estimated that several hundred Prisms could whip through a molecule of human DNA in a few weeks, although only in a rough way. To fill in the gaps—places where the DNA code came out garbled or wasn’t read properly by the machines—it would be necessary to sequence the molecule again and again. This is known as repeat sequencing, or manyfold coverage, and he thought it might take a few years. Hunkapiller persuaded the chief executive of Perkin-Elmer, Tony White, to restructure the business and create a genomics company.

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.

ONE 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.”

THE 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.”

AT CELERA’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.

Craig Venter stood watching the robots move. The room smelled faintly like the contents of a human intestine. “This used to be done by hand,” he said. All the human DNA fragments would eventually wind up in the Prism sequencing machines, and what would be left, at the end, was a collection of up to twenty-two million random fragments of sequenced human DNA. Then the river of shattered DNA would come to the supercomputer, and to a computer scientist named Eugene Myers, who with his team would assemble all the broken bits of human code into the more-or-less correct order, producing the full human genome.

GENE MYERS had dark hair and a chiseled, handsome face. He wore glasses, a green half-carat emerald in his left ear, and brown Doc Martens shoes. He also had a ruby and a sapphire that he would wear in his ear, instead of the emerald, depending on his mood. He was sensitive to cold. On the hottest days of summer, Myers wore a yellow Patagonia fleece jacket, and he kept a scarf wrapped around his neck. “My blood’s thin,” he explained to me. He said the scarf was a reference to the DNA of whatever organism he happened to be working on. When I first met Myers, he was keeping himself warm in his fruit-fly scarf. It had a black-and-white zigzag pattern. Later, Myers started wearing his human scarf, which had a green chenille weave of changing stripes. He intended his scarf to make a statement about the warfare between Celera and the public project. “I picked green for my human scarf because I’ve heard that green is a positive, healing color,” he said. “I really want all this bickering to go away.” His office was a cubicle in a sea of cubicles, most of which were stocked with Nerf guns, Stomp Rockets, and plastic Viking helmets. Occasionally, Myers would put “Ride of the Valkyries” on a boom box, and in a loud voice he would declare war. Nerf battles swept through Celera whenever the tension rose. Myers fielded a compound double-action Nerf Lock ’n Load Blaster equipped with a Hyper Sight. “Last week we slaughtered the chromosome team,” he told me.

IN THE FALL, Venter announced that Celera had completed the sequencing of the fruit fly’s DNA and had begun to run human DNA through its sequencing machines—there were now three hundred of them crammed into Building One in Rockville. The Command Center was up and running, and from then on Celera operated in high-speed mode. One day that fall, I talked with the company’s information expert, a stocky man named Marshall Peterson. He took me to the computer room, in Building Two. To get into the room, Peterson punched in a security code and then placed his hand on a sensor, which read the unique pattern of his palm. There was a clack of bolts sliding back. We pushed through the door.

A chill of cold air washed over us, and we entered a room filled with racks of computers that were wired together. “We have fifty-five miles of fiber-optic cables running through this building,” Peterson said. Workmen standing on ladders were installing many more cables in the ceiling. “The disk storage in this room is five times the size of the Library of Congress. We’re getting more storage all the time. We need it.”

He took me to the Command Center, where a couple of people were hanging around consoles. A big screen on the wall showed CNN Headline News. “I’ve got a full-time hacker working for me to prevent security breaches,” Peterson said. “We’re getting feelers over the Internet all the time—people trying to break into our system.” Celera would be dealing with potentially valuable information about the genes of all kinds of organisms. Peterson thought that some of what he called feelers—subtle hacks and unfriendly probes—had been emanating from Celera’s competitors. He said he could never prove it, though. Lately, the probes had been coming from computers in Japan. He thought it was American hackers co-opting the Japanese machines over the Internet.

By October 20, forty days after Celera started running human DNA through its machines, the company announced that it had sequenced 1.2 billion letters of human code. The letters came in small chunks from all over the genome. Six days later, Venter announced that Celera had filed provisional patent applications for sixty-five hundred human genes. The applications were for placeholder patents. The company hoped to figure out later which of the genes would be worth patenting in earnest.

A gene patent gives its holder the right to make commercial products and drugs derived from the gene for a period of seventeen years. Pharmaceutical companies argue that patents are necessary, because without them businesses would never invest the hundreds of millions of dollars needed to develop a new drug and get it through the licensing process of the Food and Drug Administration. (“If you have a disease, you’d better hope someone patents the gene for it,” Venter said to me.) On the other hand, parceling out genes to various private companies could lead to what Francis Collins referred to as the “Balkanization of the human genome,” a paralyzing situation that might limit researchers’ access to genes.

Venter insisted that Celera was an information company and that patenting genes was not its main goal. He had said that Celera would attempt to get patents on not more than about three hundred human genes. Even so, it was pretty clear that Celera was hoping to nail down some very valuable real estate in the human genome—billion-dollar genes, perhaps.

All summer long, Celera’s stock had bounced around between seven and ten dollars a share. Around Halloween, as investors began to realize that the company was cranking out the human genome—and filing large numbers of patents on genes—the stock jumped up to twenty dollars a share. On December 2, the Human Genome Project announced that it had deciphered most of the code on chromosome no. 22, the second-shortest chromosome in the human genome. This made the reading of the whole genome seem doable and imminent, and Celera’s stock began a spectacular, tornadic rise of a sort that has rarely been seen in the American stock market. It shot up that day by nine points, and closed at over seventy dollars. Then, after the market’s close on Thursday, December 16, Tom Gardner, a cofounder of the Web site called the Motley Fool, announced that he was buying shares of Celera for his own portfolio. It was known as the Rule Breaker Portfolio, and it featured small companies that broke the rules and changed the landscape of business.

Celera came of age during the huge rise of the Internet stock-market bubble. When the news broke that Celera had been named to the Motley Fool’s Rule Breaker Portfolio, a large number of people tried to buy Celera the next morning. They drove the stock up twenty points in a matter of minutes. A few months earlier, it had been trading at seven dollars a share. Celera’s stock price looked like it was headed for Mars.

I went to visit Celera one day the following week. On that particular morning the company’s stock could not even open for trading on the New York Stock Exchange. That morning, it seemed as though all of Wall Street wanted to buy Celera. That morning a tsunami of buy orders for Celera overwhelmed the specialists on the floor of the New York Stock Exchange. Trading in Celera froze, while the traders on the floor of the New York Stock Exchange waited for sell orders to trickle in. While the stock was halted—at $101 a share—I wandered around the building.

There was a feeling of shock in the air. Everyone was aware of the trading halt in the stock; everyone in the building owned Celera stock. Just about every employee of Celera was becoming a multimillionaire, and it seemed to be happening by the minute. I felt that very little work was getting done that day at Celera, except by the robots. Employees were checking the stock quote on Yahoo! and wondering what their net worth would be in an hour or two, when the stock would finally open and start trading.

I found Hamilton Smith in his lab, puttering around with human DNA in tiny test tubes. He seemed to be the only person at the company who wasn’t very affected by the situation. He was tired and looked sleep-deprived. He explained that he was renovating his house and had stayed up all night ripping carpet out of the basement. “The carpet guys were coming in to lay new carpet in the basement, and I didn’t feel like paying them to rip out the old carpet,” he said. “It would have been expensive.” Hamilton Smith owned many thousands of shares of Celera, and his net worth was already in the many millions. He also refused to buy a new car. He had driven to work that day, as usual, in his ’83 Mercury Marquis.

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.”

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.

Craig Venter lost his job at the moment when Celera’s stock was already crashing, and his firing from Celera caused the stock go into free fall, headed for near zero, it seemed. Venter had to sell all of his shares in Celera upon his exit from the company, and he sold them at the very bottom. He ended up walking away with about one million dollars in his pocket after his adventure with Celera. “I made a million dollars the hard way,” he remarked. “I started with a billion dollars and lost it.”

AFTER HE LEFT CELERA, Craig Venter went sailing. He still had some assets left, including shares in a company called Diversa, which he had cofounded years earlier. He had also sold Sorcerer (the yacht in which he’d won the Transatlantic Challenge) and he had gotten a few million dollars from that. He took some of the money and bought a used sailing yacht, a ninety-four-foot sloop, named it Sorcerer II, and outfitted it as a marine research vessel. He raised federal and private funding, hired a crew, and went on a voyage to circumnavigate the earth, following the idea of the HMS Challenger expedition of the 1870s, when the British sailing ship went on the first oceanographic expedition to explore the depths of the earth’s oceans. “I was telling people that all I hoped to get out of this deal was a bigger yacht,” he said.

The Sorcerer II sailed thirty-three thousand miles. Every two hundred miles, Venter and his colleagues stopped the boat and took samples of seawater. These bottles of water were sent back to the laboratory of a nonprofit foundation called the J. Craig Venter Institute, in Rockville, which Venter had established and ran.

Seawater is loaded with viruses, bacteria, and single-celled organisms. Therefore it’s a soup with DNA floating around in it. The samples of seawater were run through DNA-sequencing machines, and the resulting fragments of DNA code were assembled in a supercomputer that looked for patterns. Venter was probing the sea, the heart of the earth’s ecosystems, for undiscovered genes. To the great surprise of biologists, Venter’s expedition revealed that the oceans are filled with millions of distinctly different and previously unknown species of microorganisms. The sea contained a vast, almost incalculable number of unknown life-forms, invisible to the eye. Especially viruses. The oceans of the earth appeared to contain perhaps a hundred million different kinds of viruses, virtually none of which were known to science, as well as countless millions of species of bacteria and single-celled organisms that had never been seen before.

Meanwhile, Craig Venter and Claire Fraser, who was the head of TIGR, had a divergence in their love lives and got divorced. Fraser left TIGR and moved to the University of Maryland, and eventually TIGR was merged into the J. Craig Venter Institute. This institute became a respected force in genomics. It had five hundred employees. Many of them, including Hamilton Smith, had exited from Celera en masse to follow Venter wherever he went.

Craig Venter had never given up sequencing the human genome. In the fall of 2007, he published a superaccurate and complete version of his own genome. Craig Venter’s genome had both sets of chromosomes in it (humans have a double set of chromosomes in each cell). This was a so-called diploid human genome, and it had more than six billion letters in it. It was twice as long as the Human Genome Project’s human genome. Craig Venter’s genome was the most finished, accurate, complete image of the human DNA that will likely be published.

He made his entire DNA code available for free on the Internet, as well. Thus anyone who wanted to know how Craig Venter, as an example of the human species, was constructed could read his blueprint on the Web site. The government may have thought it was only cruising, but Venter had never stopped racing.

CRAIG VENTER’S latest project was to create life in a test tube. He called it synthetic biology. The leader of the synthetic biology effort at at the J. Craig Venter Institute was Hamilton Smith. Smith, who had made and lost millions in the Celera venture, had finally sold his ’83 Mercury Marquis and replaced it with a white Cadillac. Now Smith, Venter, and their colleagues were creating artificial genes—making stretches of DNA in the laboratory, rather like typing words with a typewriter. They were putting the machine-made DNA into bacteria. Their goal was to create synthetic organisms, microbes made by man to serve man. These laboratory-made bacteria, Venter and Smith hoped, would be able to digest cellulose plant material, such as in grass and pulpwood, ultimately turning it into ethanol, which could be used to power automobiles in place of gasoline.

Venter had founded a private company—for profit—called Synthetic Genomics. “We have some major deals with companies, such as one with BP [British Petroleum] to develop synthetic bacteria that would metabolize coal and turn it into natural gas,” he said. “We’re developing bacteria that can convert carbon dioxide that’s been sequestered from the burning of coal and turn it into methane [for use in natural gas]. We’ve engineered a cell line”—a strain of living cells—“that could produce a new biological fuel that would replace jet fuel,” he said. In this way, Craig Venter and Hamilton Smith hoped to help reduce global climate change while getting rid of America’s dependence on foreign oil, all made possible by advances in the reading and writing of DNA. Along the way, Venter and his colleagues decoded the DNA of the dog. The dog DNA came from Shadow, one of Craig Venter and Claire Fraser’s poodles. The last I heard, Shadow was living with Claire and doing fine. “I have visitation privileges with Shadow but see him rarely,” Venter said.