Panic in Level 4

(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.

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