From The New
Yorker
Craig Venter is an asshole. 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 recently. The Human Genome Project is a
nonprofit international research consortium that since the late nineteen-
eighties has been working to decipher the complete sequence of nucleotides 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. It
is often referred to as the book of human life, and most scientists agree that
deciphering it will be one of the great achievements of our time. The stakes,
in money and glory, to say nothing of the future of medicine, are huge.
In the United States, most of the
funds for the Human Genome Project come from the National Institutes of Health,
and it is 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 is 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 are
doing is preparing to announce, in the next few days or weeks, that they have
placed in the proper order something like ninety-five per cent of the readable
letters in the human genetic code. They refer to this milestone as First
Assembly. They have already started selling information about the genome to
subscribers. The Human Genome Project is also on the verge of announcing a
milestone: what it calls a "working draft" of the genome, which is
more than ninety-per-cent complete and is available to anyone, free of charge,
on a Web site called Gen-Bank. It contains a large number of fragments that
have not yet been placed in order, but scientists in the public project are
scrambling to get a more complete assembly. Both images of the human
genome--Celera's and the public project's-are becoming clearer and clearer. The
human book of life is opening, and we hold it in our hands.
A human DNA molecule is about a
metre long and a twenty-millionth of a metre wide-the width of twenty hydrogen
atoms. It is shaped like a twisted ladder, and each rung of the ladder is made
up 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, about the number of letters in two thousand copies of
Moby-Dick.
Perhaps three per cent of the
human code consists of genes, which hold 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 protein. It is believed that there are somewhere between thirty thousand
and possibly more than a hundred thousand genes in the human genome (there's great
puzzlement about the number). 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, and
both Celera and the public project plan to publish annotated versions of the
human genome later in 2000, perhaps in Science. It is even possible that they
will announce a collaboration and publish together. Although right now the two
sides look like armies maneuvering for advantage, the leaders of the Human
Genome Project
have consistently denied that they
are involved in some kind of competition.
"They're trying to say it's
not a race, right?" Craig Venter said to me recently, 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, 'We weren't racing-we were just cruising."'
I FIRST MET Craig Venter on a
windy day in summer nearly a year ago, at Celera's headquarters in Rockville,
Maryland, a half-hour drive northwest of Washington, D.C. The company's offices
and laboratories occupy a pair of five-story white buildings with mirrored
windows, surrounded by beautiful groves of red oaks and tulip-poplar trees. One
of the buildings contains rooms packed with row after row of DNA-sequencing
machines of a type known as the ABI Prism 3700. The other building holds what
is said to be the most powerful civilian computer array in the world; it is
surpassed only, perhaps, by that of the Los Alamos National Laboratory, which
is used for simulating nuclear bomb explosions. This second building also
contains the Command Center, a room stuffed with control consoles and computer
screens. People in the Command Center monitor the flow of DNA inside Celera.
The DNA flows through the Prism machines twenty-four hours a day, seven days a
week.
That day last summer, 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 shit out of everybody,
including ourselves," he said to me. Venter is fifty-three years old, and
he has an active, cherubic face on which a smile often flickers and plays. He
is bald, with a fuzz of short hair at the temples, and his head is usually
sunburned. He has bright-blue eyes and a soft voice. 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 looks into the trees, and
that day leaves were spinning on branches outside the windows, flashing their
white undersides and promising rain. Beyond the trees, a chronic traffic jam
was occurring on the Rockville Pike. Celera is in an area along a stretch of
Interstate 270 known as the Biotechnology Corridor, which is dense with companies
specializing in the life sciences.
Celera Genomics is a part of the
P.E. Corporation, which was called Perkin-Elmer before the company's chief
executive, Tony L. White, split the busines's into two parts: P.E. Biosystems,
which makes the Prism machine, and Celera. Venter owns five per cent of
Celera's stock, which trades, often violently, on the New York Stock Exchange.
In recent months, the stock has been tossed by waves of panic selling and panic
buying. Currently, the company is valued at three billion dollars, more or
less. At times, Craig Venter's net worth has slopped around by a hundred
million dollars a day, 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 believes, for
example, that one day Celera will help analyze the genomes of millions of
people as a regular part of its business-this will be done over the Internet,
he says-and the company will then help design or select drugs tailored to
patients' particular needs. Genomics is moving so fast that it is possible to
think that in perhaps fifteen years you will be able to walk into a doctor's
office and have your own genome 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.) Doctors would read the smart card, and it would show a
patient's total biological-software code. They could see the bugs in the code,
the genes that make you vulnerable to certain diseases. Everyone has bugs in
his code, and knowing what they are will become a key to diagnosis and
treatment. 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 the body was responding to
treatment. All your genes could be observed, operating in an immense symphony.
Venter stopped moving briefly, and
sat down in front of a screen and tapped a keyboard. A Yahoo! quote came tip.
"Hey, we're over twenty today," he said. (Celera's stock has since
split. Adjusted for today's prices, it was trading at ten dollars a share; at
the time of this writing, it was trading at around seventy dollars a share.) I
was standing in front of a large model of Venter's yacht, the Sorcerer, in
which he won the 1997
Trans-Atlantic Race in an upset
victory-it was the only major ocean race that Venter had ever entered. "I
got the boat for a bargain from the guy who founded Land's End," Venter
said. "I like to buy castoff things on the cheap from ultra-rich
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 a
smell of paint and spackle drifted in the air. We took the stairs to the
basement and entered a room that held about fifty ABI Prism 3700 machines. Each
Prism was the size of a small refrigerator and had cost three hundred thousand
dollars. Prisms are 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. Heat from the lasers seemed to ripple
from the machines, even though they were being cooled by a circulation system
that drew air through them. 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 a hundred and fifty
Prisms-forty- five million dollars' worth of the machines-and more Prisms were
due to be installed any day. Air ducts dangled on straps from the ceiling, and
one wall consisted of gypsum board.
Venter moved restlessly through
the unfinished space. "You know, 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 per cent of what will be known about biology, human physiology, and
medicine. My view of biology is 'We don't know shit.' "
Celera's business model provokes
some interesting questions, and some observers believe the company could fail.
For instance, it appears to be burning through at least a hundred and fifty
million dollars a year. But who will want to buy the information the company is
generating, and how much will 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'll do the mouse, rice, rat, dog, cow, corn, maybe apple
trees, maybe clover. We'll do the chimpanzee.
ONE DAY AT Celera's headquarters,
I was talking with a molecular biologist named Hamilton O. Smith, who won a
Nobel Prize in 1978 as the co-discoverer of restriction enzymes, which are used
to cut DNA in specific places. Scientists se the enzymes like scissors,
chopping up pieces of DNA so that they can be ludied or recombined with the DNA
of other organisms. Without the means do this, there would be no such thing
as genetic engineering.
Ham Smith is in his late sixties.
He is six feet five inches tall, with a shock of stiff white hair and a modest
manner. "Have you ever seen human DNA?" he asked me, as he poked
around his lab.
"No."
"It's beautiful stuff."
A box that held four small plastic
tubes, each the size of a pencil stub, sat on a countertop. "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 held up one of the tubes and
turned it over in the light to show me. A droplet of clear liquid moved back
and forth. It was the size of a dewdrop. Then he held up a glass vial, and
rocked it back and forth, and a crystal-clear, syrupy liquid oozed around in
it. He explained that this was DNA he'd exacted from human blood-from white
cells. "That's long, unbroken DNA. This liquid looks glassy and clear, but
it's snotty. It's like sugar syrup. It really a sugar syrup, because there are
sugars in the backbone of the DNA molecule.'
Smith picked up a pipet- a
hand-held device with a hollow plastic needle it, which is used for moving tiny
quantities of liquid from one place to another. His hands are large, but they
moved with precision. Holding the pipet, he sucked up a droplet of DNA mixed
with a type of purified salt water called buffer. He held the drop in the pipet
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 spaghetti failing out of a pot, causing the
water to string out. "It's absolutely glassy clear, without color,"
he said. "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 molcule is actually quite stiff. It's 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 is
using are kept in a freezer near Smith's ice. When he wants to get some human
DNA, he removes a vial of frozen white blood cells or sperm from the freezer.
The vials have coded labels. He thaws the sample of cells or sperm, then mixes
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 pops the eggs and the
yolks, and strands of DNA spill out in the salt water. The debris falls to the
bottom, 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 pipet, she drew a tiny amount of liquid from a tube and let a
drop go on 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.
DNA FROM SIX DONORS who
contributed their blood or semen was used for Celera's human-genome project.
The donors included both men and women, and a variety of ethnic groups. Just
one person, a man, supplied the DNA for First Assembly. Only Craig Venter and
one other person at the company are said to know who the donors are. "I
don't know who they are, but I wouldn't be surprised if one of them 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. His family's house was near the railroad tracks. One of his favorite
childhood activities, he says, was to play chicken on the tracks. In high
school, he excelled in science and shop. He built two speed boats, and spent a
lot of time surfing Half Moon Bay. He attended two junior colleges in a desultory
way, but mostly he surfed, until he enlisted in the Navy. He had long blond
hair and a crisp body then. He was a medical corpsman in Vietnam, and twice he
was sentenced to the brig for disobeying orders.
Venter has a history of
confrontation with government authorities. He told me that as an enlisted man
in San Diego he was court-martialled 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 his, Ron Nadel, who was a doctor in Vietnam, recalls 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 calculates, more than a
thousand Vietnamese and American soldiers died during his shifts, many of :hem
while the 1968 Tet offensive was going on. When he returned to the United
States, Venter finished college and then earned a Ph.D. in physiology and
pharmacology from the University of California at San Diego.
Venter is married to a molecular
biologist, Claire Fraser, who is the president of The Institute for Genomic
Research (TIGR, pronounced "Tiger"), in Rockville, a nonprofit
institute that he and Fraser helped establish in 1992. In 998, he endowed TIGR
with half of his original stake in Celera-five per cent of the company. The
gift is currently worth about a hundred and fifty million dollars, and it will
be used to analyze the genomes; of microbes that cause malaria and cholera and
other diseases.
A few years ago, Venter developed
a hole in his intestine, due to diverticulitis. He collapsed after giving a
speech, and nearly died. He is fine now, but he blames stress caused by his
enemies for his burst intestine. Venter has enemies of the first water. They
are brilliant, famous, articulate, and regularly angry. At times, Venter seems
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 seems baffled, and says he can't understand why they
don't like him.
ONE OF VENTER'S most venerable
enemies is James Watson, who, with Francis Crick and Maurice Wilkins, won the
Nobel Prize in Medicine in 1962 for discovering the shape of the DNA
molecule-what they called the double helix. Watson helped found the Human
Genome Project, and he was the first head of the N.I.H. genome program. I
visited him in his office at the Cold Spring Harbor Laboratory, on Long Island.
The office is panelled in blond oak and has a magnificent eastward view across
Cold Spring Harbor. Watson is now in his seventies. He has a narrow face,
lopsided teeth, a frizz of white hair, sharp, restless eyes, a squint, and a
dreamy way of speaking in sentences that trail 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. "No chernist
ever thought we could read the molecule." But a number of biologists began
to think that reading the human genome might just be possible, and by the
mid-nineteen-eighties 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.
Watson appeared before Congress in
May of 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 is now 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 include one at Baylor University in Texas, one at Washington
University in St. Louis, the Whitehead Institute at M.I.T., 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-is funding the Sanger work, which is 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 N.I.H., 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 E.S.T.s, which are fragments of DNA at the ends of genes.
When the E.S.T.s 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 N.I.H., 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 three hundred and fifty human genes. The method was not
received well by many genomic scientists. It was fast, easy, and powerful, but
it didn't look elegant, and some scientists seemed threatened by it. Venter
claims that two of his colleagues, who are now heads of public genome centers,
asked him not to publish his method or move forward with it for fear they would
lose their funding for genome sequencing.
The N.I.H. decided to apply for
patents on the gene fragments that Venter had identified. James Watson blew his
stack over the idea of anyone trying to patent bits of genes, and he got into a
hostile situation with the director of the N.I.H., Bernadine Healy, who
defended the patenting effort. In July of 1991, during a meeting in Washington
called by Senator Pete Domenici, of New Mexico, to review the genome program,
Watson dissed Venter's methods. "It isn't science," he said, adding
that the 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."
Today, James Watson insists that
he wasn't 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 to me. The patent office turned down the N.I.H.'s application, but a few
years later, two genomics companies, Incyte and Human Genome Sciences, adopted
the E.S.T. method for finding genes, and it became the foundation of their
businesses-currently worth, combined, about seven billion dollars on the stock
market. Incyte and Human Genome Sciences are Celera's main business
competitors. Samuel Broder, the chief medical officer at Celera, who is a
former director of the National Cancer Institute, said to me, heatedly,
"None of the people who severely and acrimoniously criticized Craig for
his E.S.T, method ever said they were personally sorry. They ostracized Craig
and then went on to use his method with never an acknowledgment."
James Watson now says, "The
E.S.T. method has proved immensely useful, and it should have been encouraged.'
VENTER WAS INCREASINGLY UNHAPPY at
the N.I.H. 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 E.S.T. sequencing,
but his request was denied by the genome project. Venter returned the grant
money with what he says was a scathing letter to Watson. In addition, Claire
Fraser had been denied tenure at the N.I.H. Her review committee (which was
composed entirely of middle-aged men) 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 N.I.H. for sex discrimination.
Watson was forced to resign as
head of the genome project in April of 1992, in part because of the dispute
over patenting Craig Venter's work. That summer, Venter was approached by a
venture capitalist named Wallace Steinberg, who wanted to set up a company that
would use Venter's E.S.T. 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 says. But 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 N.I.H. and founded TIGR, which is a nonprofit
organization. At the same time, 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 (the organism that lives in the human gut), but
no genome of any organism had been completed, except virus genomes, which are
relatively small. Venter and Hamilton O. Smith (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.
Venter and Smith applied for a
grant from the N.I.H. to shotgun-sequence the genome of a disease-causing bacterium
called H. 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 N.I.H. 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, and 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. 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 review panel seems to have
hated the idea of giving N.I.H. money to TIGR to make discoveries that would be
turned over to a corporation, Human Genome Sciences. It turned down the grant,
in spite of the fact that "all the smart people knew the method was
straightforward and would work," Eric Lander, the head of the genome
center at M.I.T. and one of the leaders of the public project, said to me.
Around this time, Wallace
Steinberg died of a heart attack, and his death provided a catalyst for a split
between TlGR and Human Genome Sciences, which was run by a former AlDs
researcher, William Haseltine. Venter and Haseltine were widely known to
dislike each other. Venter 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
false. This did not win Venter many friends. But he seemed to have a point.
Francis Collins, a distinguished
medical geneticist from the University of Michigan, had become the head of the
N.I.H. genome program shortly after James Watson resigned in 1992. In early
January, 1998, an internal budget projection from Collins's office somehow
found its way to Watson (he seems to find out everything that's happening in
molecular biology). This budget projection it is not clear whether it was
formal or was just an unofficial projection-was a document about eight pages
long. It contained a graph marked "Confidential" indicating that
Collins planned to spend only sixty million dollars per year on direct
human-DNA sequencing through 2005. It also predicted that by that year-when the
human genome was supposed to be completed-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.
This upset Watson, and he decided
to discuss it with Eric Lander. On January 17th, Watson travelled to
Rockefeller University, on the East Side of Manhattan, where Lander was giving
the prestigious Harvey Lecture. The two men met after the lecture at the
faculty club at Rockefeller. They were dressed in black tie and were somewhat
inebriated. Traditionally among medical people, the Harvey Lecture is given and
listened to under the influence.
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 smal 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 is
one of Watson's best friends. Zinder, like Watson, is 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 Collins did not intend to spend more than sixty
million dollars a year on human-DNA sequencing-nowhere near enough to get the
job done, they felt.
Watson evidently felt that 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 potchkeeing 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. This was intolerable. The
human genome had begun to seem like a vision of Canaan to Norton Zinder, and he
thought lie 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.
Implicitly, he thought its leader should be Eric Lander.
The three men downed their cognacs
with a sense of frustration. "I had essentially given up seeing the human
genome in my lifetime," 'Zinder says.
AT ABOUT THE SAME MOMENT that
Watson and his friends were lamenting the slowness of the public project, the
Perkin-Elmer Corporation, which was a manufacturer of lab instruments, was
secretly talking about a corporate reorganization. It controlled more than
ninety per cent of the market for DNA-sequencing equipment, and it was
developing the ABI Prism 3700. The Prism was then only a prototype sitting in
pieces in a laboratory in Foster City, California, but already it looked as if
it were 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 Hunkapillar, 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 might take a few years. Hunkapillar 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 Venter to see if he'd be interested in running
the new company. He blew them off at first, but in early February, 1998, he went
to California with a colleague, Mark Adams, to look at the prototype Prism.
When they saw it, they immediately understood its significance. Before the end
of that day, Venter, Adams, and Hunkapillar had laid out a plan for decoding
the human genome. A month later, Norton Zinder, Watson's friend, flew to
California to see the machine. "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 has considerably enriched him. ("The chemists have
been cleaning up," he said to me. "Now biologists have their hands on
the money, too. .") Zinder and Watson have maintained their friendship but
have agreed not to speak about Celera with each other. They evidently fear that
one or both of them could have a stroke arguing about Craig Venter.
AT ELEVEN O'CLOCK in the morning
on May 8, 1998, Craig Venter and Mike Hunkapillar walked into the office of
Harold Varmus, who was then the director of the N.I.H., and announced the
pending formation of a corporation, led by Venter, that was going to decode the
human genome. (Celera did not yet have a name.) They 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, including the unspoken possibility of a Nobel Prize. Varmus strongly
suspected that this wasn't a sincere offer, and he told them that he needed
time, particularly to check with Francis Collins. Later that same day, Venter
and Hunkapillar drove to Dulles Airport, where they met Collins at the United
Airlines Red Carpet Club, and again offered collaboration. Venter recalls that
Collins seemed upset. Collins recalls that he merely asked Venter for time to
consider the offer. Time was one thing Venter was not prepared to give.
Venter had alerted the New York
Times to the story about the creation of the new company, and just an hour or
so after the meeting with Collins he called the Times and told the paper it
should run it. In the story, Venter announced that he would sequence the human
genome by 2001-four years ahead of the public project-and he would do it, he
claimed, for between a hundred and fifty and two hundred million dollars-less
than a tenth of the projected cost of the public project. The Times reporter,
Nicholas Wade, implied that the Human Genome Project might not meet its goals
and might be superfluous.
Four days later, on May 12th,
Venter and Hunkapillar went to the Cold Spring Harbor Laboratory, 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 stop working, since he was going
to sequence the human genome tout de suite. Later that week, sitting beside
Varmus and Collins at a press conference, Venter looked out at a room full of
reporters and suggested that biology and society would be better off if the
Human Genome Project shifted gears and moved forward to do the genome of the
... mouse.
it was a fart in church of
magnitude nine. "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. Venter said that he would make the genome available to the public
but would charge customers who wanted to see and work with Celera's analyzed
data.
James Watson was furious. He did
not like the idea of having to pay money to Craig Venter for anything. Watson
did not attend Venter's presentation, but he appeared in the lobby afterward,
where he repeatedly 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, and he and Watson have exchanged only chilly greetings since.
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 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 in fibrillation,
with scientists wondering if the Human Genome Project was about to die. To a
standing ovation, Michael Morgan got up and read a Churchillian statement
declaring that the Wellcome Trust would nearly double its funding for the
public project, and would decode a full third of the human genome, 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 says now.
Venter also announced that Celera
would use the whole-genome shotgun method. The public project was using 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 says now
that his words were taken out of context, and he regrets the quote.
THE COMPANY FORGED from
Perkin-Elmer amid the turmoil was the P.E. Corporation, which holds the P.E.
Biosystems Group, the unit that makes the Prism machines, and Celera Genomics.
Michael Hunkapillar, who is now the president of P.E. Biosystems, believed that
he could sell a lot of machines to everyone, including the Human Genome
Project. There was a fat profit margin in the chemicals the machines use. The
chemicals cost far more than the machine over the machine's lifetime. This was
the razor-blade principle: if you put razors in people's hands, you will make
money selling blades.
In August, Incyte Pharmaceuticals
announced that it was starting a human-genome project of its own. In September,
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 by 2001 - a year ahead of when Venter said he'd
be done-and a finished, complete version by 2003. An epic race had begun.
A couple of months ago, Michael
Morgan, of the Wellcome Trust, was talking to me about Venter and what 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
project, and said that he had turned down a job offer from Celera. He didn't
have any illusions about human nature. 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 N.I.H. was suddenly forced to
consolidate its funding. The N.I.H. and Francis Collins began to dump more than
eighty per cent of the money into just three centers-Baylor, Washington
University, and M.I.T. -- and they jacked everybody else. They had to do it,
because they had to race Cetera, and they couldn't control too many players. So
all but three centers were cut drastically, and some of the labs closed down.
Cetera 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.' That's the reason so many of
them are so angry at Cetera. It's easier for them to go after Craig than to go
after Francis Collins and the N.I.H."
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.
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. We've been picking fifty-five thousand
clones a day," he said. (Later, Cetera got that rate up to a hundred and
twenty thousand clones a day.) All the 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 computer, and to a computer
scientist named Eugene Myers, who with his team devised the First Assembly.
Gene Myers has dark hair and a
chiselled, handsome face. He wears glasses and a green half-carat emerald in
his left ear and brown Doc Martens shoes. He also has a ruby and a sapphire
that he will wear in his ear, instead of the emerald, depending on his mood. He
is sensitive to cold. On the hottest days of summer, Myers wears a yellow
Patagonia fibrepile jacket, and he keeps a scarf wrapped around his neck.
"My blood's thin," he explained to me. He says the scarf is a
reference to the DNA of whatever organism he happens to be working on. When I
first met Myers, in the hot summer of 1999, he was keeping himself warm in his
fruit-fly scarf. It had a black-and-white zigzag pattern. This spring, Myers
started wearing his human scarf, which has a green chenille weave of changing
stripes. He intended his scarf to make a statement about the warfare between
Cetera 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 is a cubicle in a
sea of cubicles, most of which are stocked with Nerf guns, Stomp Rockets, and
plastic Viking helmets. Occasionally, Myers puts the "Ride of the
Valkyries" on a boom box, and in a loud voice he declares war. Nerf
battles sweep through Cetera whenever the tension rises. Myers fields a
compound double-action Nerf Lock-N-Load Blaster equipped with a Hyper*Sight.
"Last week we slaughtered the chromosome team," he said to me.
Myers used to be a professor of
computer science at the University of Arizona in Tucson. He specializes in
combinatorial algorithms. This involves the arrangements and patterns of objects.
One day in 1995, he got a telephone call from a geneticist named James Weber,
at the Marshfield Medical Research Foundation in Wisconsin. Weber said he felt
that whole-genome shotgunning would work for organisms that have very long DNA
molecules, such as humans. He wondered if Myers could help him with the math.
Jim Weber submitted a proposal to
the N.I.H. for a grant-twelve million dollars-to support a pilot study of the
shotgun approach on the human genome. This might speed up the project
dramatically, he suggested. Weber was invited to speak to the annual meeting of
the heads of the project, held in Bermuda.
Weber was nervous about it, and
wanted Gene Myers to go with him to help explain the math. "Jim asked them
to invite me, but they didn't," Myers says. So on February 26, 1996, Jim
Weber went alone to the meeting in Bermuda and tried to make a case for
shotgunning the human genome. He found himself facing a U-shaped table with
about forty people at it. "They trounced Jim," Myers said. "They
said it wouldn't work. They said it would be full of holes. 'A Swiss-cheese
genome'-that's the term we've often heard. The grant proposal was soundly
rejected.'
Jim Weber says that the
Swiss-cheese analogy was not far off, but that "it would have been much
better to get most of the human genome quickly, even with holes in it, so that
people could start using the information to understand diseases and begin to
find cures for them. It would have been better if the N.I.H. had funded a pilot
study. Instead, Gene and his team went out and did it. That is a huge
accomplishment.'
Craig Venter was hanging around
while I was talking with Myers. He came up to us and said, "They not only
shot Gene down-they ridiculed him. They said he was a kook. We're going to
prove that Gene was right, and we're going to prove that there's something
fundamentally wrong with the system.'
ON SEPTEMBER 9, 1999, Venter
announced that Cetera 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 Cetera 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, and 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. "What you're looking at in this room is roughly the equivalent
of America Online's network of servers," Peterson said. "We have
fifty-five miles of fibre-optic cables running through this building. "
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. Some of the consoles had
not had equipment installed in them yet. 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." Cetera
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 Cetera'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 20th forty days after
Cetera 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
Cetera had filed provisional patent applications for six thousand 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 that are 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, parcelling out genes to various private companies could lead to
what Francis Collins refers to as the "Balkanization of the human
genome," a paralyzing situation that might limit researchers' access to
genes.
Venter insists that Cetera is an
information company and that patenting genes is not its main goal. He has said
that Cetera will attempt to get patents on not more than about three hundred
human genes. There is no question that Cetera hopes to nail down some very
valuable genes -- billion-dollar genes, perhaps.
CELERA'S STOCK HAD DRIFTED since
the summer, but around Halloween, as investors began to realize that the
company was cranking out the human genome-and filing large numbers of
placeholder patents-it jumped up to forty dollars a share. (The prices here are
pre-split prices. Adjusted for today's prices, the stock moved up to twenty
dollars.) On December 2nd, 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 more imminent, and
Cetera's stock began a spectacular rise. It shot up that day by nine points, to
close at over seventy dollars. Then, after the market's close on Thursday,
December 16th, Jeff Fischer, a co-founder of the Web site called The Motley
Fool, announced that he was buying shares of Cetera for his own portfolio. It
is called the Rule Breaker Portfolio, and it has famously delivered
wealth-Fischer bought A.O.L. very early, for example. On that Friday morning, a
great number of people tried to buy Cetera, and they drove the stock up twenty
points. It was on its way to the pre-split equivalent of more than five hundred
dollars a share. That past summer, it had been trading at fourteen.
I went to visit Cetera on Tuesday
of the following week, and that morning the company's stock could not open for
trading. Everyone wanted to buy it, and nobody wanted to sell it. While the
stock was halted-at a hundred and one dollars a share-I wandered around. There
was a feeling of paralysis in the air, and I sensed that not much work was
getting done that day, except by the machines. Employees were checking the
quote on the Internet and wondering what their net worth would be when the
stock opened. The lobby now sported fish-eye security cameras. The walls
smelled of fresh paint, and the floors had a new purple carpet with a pattern
that resembled worms. They were meant to look like fragments of DNA.
I found Hamilton O. Smith in his
lab, Puttering around with human DNA in tiny test tubes, but his heart was not
in the job. He was tired. He explained that he was renovating an old house that
he and his wife had bought. He had stayed up all night ripping carpet out of
the basement, because new carpets were due to arrive that morning. He had
driven to work in his '83 Mercury Marquis. He owned thousands of shares of
Celera.
Smith passed a computer, stopped,
and brought up a quote. Celera had finally opened for trading. It had gapped
up-jumped instantly upward-by thirteen points. It was at a hundred and
fourteen. Smith's net worth had gapped up by something on toward a million
dollars. "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 said. "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 is a tall,
reserved woman with dark hair and brown eyes, and her voice has a faint New
England accent. She grew up in Saugus, Massachusetts. In high school, she says,
she was considered a science geek. "The only lower citizens were the nerdy
guys in the audiovisual club. Of course, now they're probably in
Hollywood." Her office has an Oriental rug on the floor and a table
surrounded by Chippendale chairs. It was originally Venter's office.
("This is Craig's extravagant taste, not mine," she explained.) She
wore an expensive-looking suit. Two poodles, Cricket 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 cholera. 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 than anyone had imagined.
Fraser's eyes moved quickly over
the diagram. "Yes ... wow... There may be important transporters here....
You see these transporters in other bacteria, and ... I don't know ... 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 a
hundred and fifty million dollars that day.
Fraser drove home, and I followed
her in my car. Their house is in the country outside Washington. It sits behind
a security gate at the end of a long driveway. Venter arrived in a 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 large stained-glass window showing branches of a
willow tree, and there was a model of H.M.S. Victory in a glass case. A jumble
of woodworking machines-a bandsaw, a table saw, a drill press-filled a shop
attached to the garage. Venter has worked with wood since 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, 1999, 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 from the earth. In
January, it soared over two hundred dollars a share. Celera filed to offer more
shares to the public, and declared a two-for-one stock split. Shortly after the
split, on February 25th, the stock hit an all-time high of two hundred and
seventy-six dollars a share (more than five hundred and fifty dollars,
pre-split). Celera's stock-market value reached fourteen billion dollars, and
Venter's worth surpassed seven hundred million dollars. It looked as if Venter
could become a billionaire of biotechnology.
Then, on March 6th, newspapers
carried reports that the discussions between Celera and the public project had
collapsed. The main point of disagreement, according to officials at the public
project, was that Celera wanted to keep control of intellectual property in the
human genome. Celera intended to license its analyzed database to
pharmaceutical companies and nonprofit research institutions, for payment.
Celera said that it would let anyone use the data, but that any other company
would be forbidden from reselling the data. The Human Genome people insisted
that the period of restriction on the data could be for no more than a year,
and after that the data should be totally public. Celera argued that it didn't
want its competitors to resell the information and profit from Celera's work.
Celera's stock began to drop.
On March 14th, President Clinton
and Prime Minister Blair of Great Britain released a joint statement to the
effect that all the genes in the human body "should be made freely
available to scientists everywhere." The statement had been drafted with
the help of Francis Collins and his staff, and had been in the works for a
year. It was vague, but it looked like an Anglo-American smart bomb aimed at
Celera, and it scared the daylights out of investors in biotechnology stocks,
who feared that potentially lucrative patents on genes might be undermined by
some new government policy.
On the day of the Clinton-Blair
statement, Celera's stock went into screaming nosedive. It dropped fifty-seven
dollars in a matter of hours, amid trading halts and order imbalances. The
other genomic stocks crashed in sympathy with Celera, and this, in turn,
dragged down the Nasdaq, which that day suffered the second-largest point loss
in its history. Short - sellers-people who profit from the decline of a
stock-encrusted Celera like locusts. As of this writing, the Nasdaq has not
recovered. Venter's mother telephoned him afterward, and said to him,
"Craig, you've managed to do overnight what Alan Greenspan has been trying
to do for years."
"It's not every day you get
attacked by the President and the Prime Minister," Venter said to me late
that night on the telephone. "I'm expecting a call from the Pope any day
now, asking me to recant the human genome." He sounded wired and
exhausted. "I feel a little like Galileo. They offered to have a barbecue
with him, 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 genome, and that's what the threat to the public order is.
If Celera was keeping the genome a secret, the way Incyte and Human Genome
Sciences are, you wouldn't hear a peep out of the government. 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 the Sanger Centre to do
just a third of the human genome, largely at the expense of the rest of British
medical science. Clinton and Blair took forty billion dollars out of the
biotechnology industry today-that's how much was lost by investors. 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."
The day after the Clinton-Blair
statement and the crash in biotech stocks, a White House spokesman made a point
of telling reporters that the Administration supported the patenting of genes.
ON MARCH 24th, Venter and his
colleagues published a substantially complete genome of the fruit
fly-Drosophila-in Science. It was also published by Celera on a CD, which
Venter had placed on the chairs of thirteen hundred fly researchers at a
conference in Pittsburgh. Venter emphasized the fact that the fly genome had
been a collaboration with a publicly funded project. In other words, he was
suggesting there was no real reason that the Human Genome Project couldn't
collaborate with Celera, too. The fly project-known as the Berkeley Drosophila
Genome Project -is headed by a fly geneticist named Gerald Rubin.
"One of the things I really
like about Craig Venter is that he almost totally lacks tact," Rubin said
to 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 "Hoover up all
the public data, which we are producing, add some of their own, and sell it as
a packaged product." He added, "The emerging truth is absolutely
extraordinary. They really do intend to establish a complete monopoly position
on the human genome for a period of at least five years," and he said,
"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." Hamilton O. Smith said to me,
shortly after his net worth had cratered in Celera's mudslide. "But the
publicly funded labs are angry for reasons I can partly understand. 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."
ON APRIL 6TH, Venter announced
that Celera had finished the sequencing phase of the human genome, and was
moving on to First Assembly. Celera had produced some eighteen million
fragments of the first genome, perhaps Craig Venter's. Soon afterward, on an
unseasonably warm day, while the cherry trees were in full blossom, I visited
Celera to see how the assembly was going. I found Gene Myers in his cubicle,
looking chilled. He was bundled up in his yellow fibrepile jacket and his green
human scarf. He and his team had started running chunks of human DNA code
through the computers over the weekend. The first run had resulted in a
mess-something was wrong with the software. They had done some tweaks, and they
were running a few more chunks of code. It would take months to assemble the
whole thing.
"Assembly is pretty
boring:'he said, somewhat apologetically.
Myers said that Celera would be
using all of the Human Genome Project's human DNA code-which was published on
the GenBank Web site-and would tear it into fragments and compare them with
Celera's DNA code, and then the software that his team had written would try to
assemble all the fragments into a whole human genome. At the same time, Celera
was coolly telling the public project that its scientists could see Celera's
data but only if they came to look at the data on Celera's computer. The
collaboration had never come to pass.
Minutes later, one of Myers's
people, a computer scientists named Knut Reinert, hurried in, and told him that
the first assembled human-genome sequence had just come out of the computers.
Myers put the "Ride of the Valkyries" on the boom box, and fifteen
people tried to crowd into Reinert's cubicle.
Myers bent over Reinert's shoulder
and said, "We got it! We got the first one! This is the first assembled
human sequence we've gotten out of nature!"
What appeared on the screen was a
mathematical diagram of a stretch of human DNA. It showed arrows going in
various directions, connecting dots together. "The picture looks like a
Super Bowl debriefing," one Celera programmer remarked.
They talked about it for a few
minutes, and then everyone drifted back to work. That day, Celera's stock
dropped another twenty per cent.
IN EARLY MAY, another company got
into the business of the human genome. DoubleTwist, Inc., announced that it had
teamed up with Sun Microsystems to compete with Celera. DoubleTwist and Sun
were offering an analyzed database of the human genome to anyone for a fee,
using the data from the Human Genome Project, not from Celera. The price was
six hundred and fifty thousand dollars for a database that would be updated regularly.
At the same time, Celera's stock
had gone down below a hundred dollars a share. Many investors had recently
bought the secondary offering, paying two hundred and twenty-five dollars a
share for it. This brought on a slew of class-action lawsuits against Celera,
filed by law firms specializing in shareholder suits. There were various
claims, sparked by the fact that the secondary investors had lost sixty per
cent of their money. These lawsuits will probably be consolidated, and Celera
will either settle or fight them in court.
As for the science, knowledgeable
observers believed that, in the end, Celera had actually spent about half a
billion dollars to sequence the human genome-three hundred million more than
Venter had originally predicted. Was it worth it? I asked many biologists about
this, and most of them spoke the way scientists do when they believe that a
great door has been opened, and light is shining deep into nature, suggesting
the presence of rooms upon rooms that have 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." He stood up, and offered me the door.
Eric Lander, who professes to like
Venter, said, "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, and
says,'There be dragons.It's as different a view of human biology as a map of
the earth in the fourteenhundreds was compared to a view from space
today." As for the war between Celera and the public project, he said,
"At a certain level, it is just boys behaving badly. It happens to be the
most important project in science of our time, and it has all the character of
a schoolyard brawl."
Norton Zinder, Watson's friend,
who had feared that he would die before he saw the human genome, said that he
felt marvellous. "I made it. Now I've gotta stay alive for four more
years, or I won't get all my options in Celera. ' Zinder, who is a
vigorous-seeming older man, 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.'