Panic in Level 4: Cannibals, Killer Viruses, and Other Journeys to the Edge of Science (20 page)

O
NE DAY AT
C
ELERA’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.

C
RAIG
V
ENTER
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.

Craig Venter as a medical corpsman in Vietnam.
Courtesy of J. Craig Venter

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.