Panic in Level 4

ON FEBRUARY 16, 2001, close to three billion letters of the human DNA in their roughly proper order were published by Craig Venter (along with two hundred coauthors) in Science magazine, under the title “The Sequence of the Human Genome.” It was a very good draft of the human genome, but it was not finished or fully accurate. That same week, the Human Genome Project published its own draft of the human genome in Nature. Taken together, these publications represented one of the monumental achievements of the twenty-first century. The implications would be with us for the rest our lives, the rest of our grandchildrens’ lives, and their grandchildrens’ lives. “Humanity has been given a great gift,” declared an editorial in Science. “This stunning achievement has been portrayed—often unfairly—as a competition between two ventures, one public and one private. That characterization detracts from the awesome accomplishment unveiled this week.”

Norton Zinder, Watson’s friend, who had feared that he would die before he saw the human genome, said that he felt marvelous. “I made it. Now I’ve gotta stay alive for four more years, or I won’t get all my options in Celera.” Zinder was convinced that Celera’s stock would rise again. (It has not recovered, so far.)

Norton Zinder was a vigorous-seeming older man. As he spoke, he was sprawled in a chair in his office overlooking the East River, gesturing with both hands raised. He shifted gears and began to look into the future. “This is the beginning of the beginning,” he said. “The human genome alone doesn’t tell you crap. This is like Vesalius. Vesalius did the first human anatomy.” Vesalius published his work in 1543, an anatomy based on his dissections of cadavers. “Before Vesalius,” Zinder went on, “people didn’t even know they had hearts and lungs. With the human genome, we finally know what’s there, but we still have to figure out how it all works. Having the human genome is like having a copy of the Talmud but not knowing how to read Aramaic.”

* * *

CRAIG VENTER ended up getting fired from Celera. The man who fired him was Tony L. White, the chief executive of Celera’s parent company (which had been renamed Applera). Tony White had been Craig Venter’s boss during the time Venter worked at Celera—even though Venter was the president of Celera, Applera owned Celera, and so was in control. It seemed that Craig Venter’s business model just wasn’t working out. Venter had figured that Celera would sell information about the human genome to subscribers, who would want to pay money for it. But not enough customers wanted to pay for it.

The problem for Celera was that the Human Genome Project kept on churning out human DNA code and, with taxpayer money, published an increasingly accurate sequence of the letters in the human DNA—published it all for free on the Internet, available to anybody at no cost. Celera couldn’t compete.

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

* * *

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

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

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

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

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

^{Craig Venter’s yacht Sorcerer II, sailing to windward in search of unknown genes.}

^{Courtesy of the J. Craig Venter Institute}

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

* * *

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

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

The Lost Unicorn