In a pristine white greenhouse in La Jolla, Calif., maverick molecular biologist Craig Venter is showing off tubs of dark green goop that might help rescue the planet.
Winter sunlight streams through the glass roof onto rows of long, white troughs filled with algae and seawater. A little water wheel in each trough turns to keep the liquid circulating and the growing cells evenly exposed to light and to carbon dioxide-enriched air. Computers maintain a constant temperature. Giant transparent bags of algae varieties waiting to be tested hang from metal beams.
This goop, Venter hopes, will someday replace oil wells, free the planet from its dependency on fossil fuels and create a near-endless supply of energy.
Jim Flatt and Paul Roessler, two senior scientists at Venter’s company, are leading guests through the greenhouse and trying not to reveal too many details about their ambitious venture. But their hypercompetitive boss, who has made a career out of shaking up the cautious culture of science — sometimes prematurely, critics say — keeps chiming in.
The strategy, Roessler explains, will be to grow oil-producing algae in concentrated conditions, “to maximize photosynthetic productivity and take up greenhouse gases at the same time.” Venter jumps in: “This is our halfway house ... a long way from the lab. The next phase is doing this in large outdoor facilities.”
Gigantic, Venter says. “We’re thinking a facility extending over multiple square miles.”
Venter and the scientists at his six-year-old company, Synthetic Genomics, are seeking strains of algae that are exceptionally good at turning carbon dioxide, water and sunlight into oil. The researchers intend to use genes from those strains to engineer algae cells that are even better at pumping out oil. Eventually, ExxonMobil, which plans to spend $600 million, $300 million of that in collaboration with Synthetic Genomics, hopes to refine oil from algae into gasoline. Other oil companies are joining biotech firms in similar efforts; Venter’s main competition may come from researchers trying to reengineer yeast or bacteria to ferment sugar into hydrocarbon fuel.
Last year, Venter’s Rockville-based J. Craig Venter Institute (JCVI) generated headlines when it said its scientists had made what they called “synthetic cells.” The announcement received plaudits from scientists, evoked alarm among some environmental groups, and prompted President Obama to ask his bioethics commission to assess the benefits and risks of the new field of synthetic biology. Although some critics called the development little more than an impressive engineering feat, Venter predicts that creating relatively simple, lab-designed cells, rather than tinkering with the genes of existing bacterial species, will become the future of biotechnology.
Back in 1998, J. Craig Venter — a former National Institutes of Health researcher — ignited a bitterly fought race to decode the human genome when he boasted that his company would beat the publicly funded, international Human Genome Project by finishing the job within three years. He even suggested that his rivals could best help out by abandoning their work on human genes and focusing on the genome of the mouse.
Now, Venter, 64, is sparking controversy once again. He has set out to do nothing less than to reengineer some of Earth’s simplest life forms to save its most complex. Once more, his claims are characteristically sweeping. Synthetic biology, he tells me, will yield new food sources, new vaccines, new tools for cleaning up the environment, and replacements for fossil fuels. It will, he says, create solutions to “all the things that are causing a lot of problems now in the world.”
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Science as magic, scientists as global explorers, DNA as the multi-potent software of life — those themes thread through Venter’s life history. His three offices — in Rockville, San Diego and La Jolla — are decorated with photos of yacht races and wooden models of sailing ships, including the Beagle, which carried Charles Darwin, the paradigm-shifting biologist Venter strives to emulate.
Venter has sailed most of the world’s oceans during the past eight years in Sorcerer II, his 92-foot research vessel. His scientists have collected samples of seawater from diverse sites to sequence the DNA of microscopic marine life, revealing a vast, previously unknown array of genomes: viruses, bacteria, algae.
For now, the yacht is undergoing repairs at a Florida boatyard while Venter divides his time between his townhouse in Alexandria and his glass-and-stucco hillside home overlooking the Pacific in La Jolla, with occasional visits to his vacation home on Nantucket.
He directs his bicoastal nonprofit research institute and heads up two companies (Synthetic Genomics and Synthetic Genomics Vaccines, a recent offshoot). He has lived in the Washington area since 1984, when he took a research position at NIH. Although these days his work and his pleasures (long motorcycle rides in the desert or photographing migrating whales) increasingly take him to California, he predicts that he and his institute will continue a Washington presence. “The government needs good science, and I’m not willing just to abdicate” the role of advising the administration and Congress on policy, he says.
Bald and white-bearded, with striking ice-blue eyes, Venter has the tan, weathered look of a lifelong sailor and an avuncular, offhand way of delivering grand, difficult-to-verify pronouncements: “We have discovered over 95 percent of all the genes that have been discovered by science off the deck of [my] sailboat,” he declares.
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When I arrive for our first meeting, at the Rockville laboratories of JCVI, I wait in a vast, deserted reception area that features a life-size wooden tiger and an odd collection of scientific memorabilia, along with a three-foot model of the first Sorcerer, the 85-foot yacht in which Venter won his first and only transatlantic sailboat race in1997 — sailing in gale-force winds and beating 19 larger boats, most captained by professionals.
Through a glass wall, I can see the legs of 10 people conferring around a table. A brown miniature poodle runs back and forth. When the meeting breaks up, the dog races out, barking. At his heels comes Venter in blue shirt and baggy jeans, cellphone on his belt. “Darwin! Come here, pup,” he orders the dog. Darwin accompanies Venter everywhere and seems to channel his master’s restless energy.
Venter loves talking about big scientific ideas, but after giving hundreds of interviews over the years, he has little appetite for filling in biographical details. “Most of this stuff you can get from my book and from a quarter of a million Web articles,” he says, handing me his autobiography. “What’s the most interesting philosophical question on your list?”
Before our next meeting, I read the book, “A Life Decoded: My Genome: My Life,” and learn that when Venter’s own genome was sequenced, it revealed he carries a gene variant associated with attention-deficit hyperactivity disorder.
In the conservative, collaborative culture of science, his style evokes a mixture of reactions. “He works on very hard projects. He’s a big risk-taker,” said Bruce Alberts, a biochemist and the editor-in-chief of Science magazine, which has published many of Venter’s studies. However, “he hypes whatever he does. ... He creates a storm around himself and often in ways that scientists like myself don’t consider appropriate.”
For instance, Venter’s use of the term “synthetic cells” to describe his team’s recent accomplishment was “a vast overstatement,” Alberts said. “It was an important contribution, but as almost always when Craig does something, the statements he makes about it are maximally designed to get attention and are distorting of the science that he’s done.”
“Craig is this guy with big ideas,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, a major funder of Venter’s. “He takes majestic leaps ... and he likes not to have any restrictions on what he can do or on the resources to get him there.”
“He isn’t content with being the brightest star in the universe — he wants to be the only star in the universe,” says John Quackenbush, a professor of computational biology and bioinformatics at Harvard School of Public Health who worked at The Institute for Genomic Research (or TIGR, founded by Venter in 1992) more than a decade ago. “Craig has done innovative work, but when he presents it, he neglects the fact that genomic science is a team endeavor.”
Yet, Venter has attracted a loyal and talented cadre of researchers who say his vision and fundraising ability have allowed them to tackle projects deemed too big or risky to be supported by the federal government.
“He doesn’t really take ‘no’ as an option,” says Karen Nelson, a tall, forthright Jamaican-born microbiologist who joined JCVI fresh out of graduate school at Cornell University in 1997 and now directs its Rockville laboratories. “In his mind, there’s no barrier to trying something.”
“We seemed to hit it off pretty well, despite what I had heard,” says Hamilton Smith, a 1978 Nobel laureate in medicine, who joined Venter at TIGR in the 1990s and has become one of his closest friends and collaborators. “I think he’s a very smart guy.”
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John Craig Venter grew up in suburban San Francisco during the 1950s and ’60s, a rebellious second child who boycotted spelling tests and earned barely passing grades, but who excelled as a competitive swimmer and as a builder. At 14, he made an eight-foot motorized hydroplane boat and sailed it on San Francisco Bay.
“My thinking is all in words — nothing visual,” he told me.
After high school, as Venter relates in his 2007 autobiography, he moved to Southern California to attend junior college, drink, chase women and bodysurf, but enlisted in the Navy after receiving his draft notice. An IQ of 142 earned him a chance to train as a medical corpsman. Soon, the 19-year-old former slacker was doing spinal taps and liver biopsies and running an infectious disease ward at Balboa Naval Hospital in San Diego. Facing deployment to Vietnam as a combat medic, an assignment he knew carried a high mortality rate, he requested an alternative posting to the Navy hospital in Da Nang.
Vietnam transformed Venter. He watched soldiers his own age die. He survived shelling and rocket attacks, and fought depression by surfing and sailing. After five months, he attempted suicide at age 21 by swimming a mile out to sea. An exploratory bump from a shark sent him flailing back to shore. “When you learn that your life is the biggest thing you have to lose, it makes you less afraid to tackle” other challenges, he says now.
More than once, his rebelliousness got him into trouble — he narrowly escaped court-martial for disobeying a female officer’s direct order — yet he found unexpected satisfaction in caring for children at a local orphanage with infections or fractures. “I learned that if you actually knew how to do things in the right ways, you could save people’s lives,” he recalls.
At the end of his Navy service, Venter returned to California, determined to become a doctor, with his fiancee, Barbara Rae, a New Zealander he had met on leave. He earned his bachelor’s degree in biochemistry, then a doctorate in physiology and pharmacology in 1975, both from the university of California at San Diego.
In 1976, he joined the faculty of the State University of New York at Buffalo. While there, he became the father of a son, Christopher, ended his marriage to Rae, and married one of his graduate students, Claire Fraser. (Christopher, now in his 30s, was a sculptor for several years after high school and graduated in June from the University of California at Santa Cruz. His father says Christopher hopes to work in bioengineering.)
By the time Venter arrived at NIH in the mid-1980s, molecular biologists had learned to decode a gene’s sequence using a laborious series of chemical reactions. When a California company, Applied Biosystems, started making automated sequencing machines, Venter bought the first one for his NIH lab. By 1987, soon after Salk Institute researcher Rene Dulbecco had suggested that scientists should decode the entire human genome, Venter was envisioning a large laboratory full of automated sequencers run by a small team of scientists. “It just became clear to me that this was going to be the way to do it,” he recalls.
The Human Genome Project, initially funded by the Department of Energy and the NIH and directed by Nobel laureate James Watson, was launched in 1990. In 1992, frustrated with leadership’s reluctance to give his laboratory a role, Venter left NIH along with his wife, Fraser, to found The Institute for Genome Research, a nonprofit in Rockville linked to a for-profit company, Human Genome Sciences, where he started to apply strategies for speeding up the sequencing process.
In 1995, a team headed by Venter and Smith published the first complete gene sequence of a free-living organism, the bacterium Hemophilus influenzae.
In 1998, Venter joined with Applied Biosystems in forming a new gene-sequencing company, Celera. He then issued his challenge to the government-run Human Genome Project. The race began, with plenty of media-fueled sniping from both sides, especially over the fact that Venter’s team had full access to the DNA sequences being generated by the public project but withheld its own data because of Celera’s plans to make money by licensing its genomic information.
In 2000, a truce was brokered and the contest declared a tie, with Venter and Francis Collins, leader of the HGP and now head of NIH, joining President Clinton at a White House announcement. Both sides say they have moved on. “After 10 years, most of the scars ... have healed,” Venter says. “I think you’d say we have a grudging mutual respect for each other.”
Collins concurs in an e-mail. “We’re co-existing just fine. Granted, we still don’t see eye-to-eye on everything — that might require some very advanced genetic engineering!”
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Venter was ousted from Celera in 2002 — the reason given was the company’s decision to focus on drug development, though internal conflict between Venter and other officials at Celera seems to have contributed — and returned to TIGR (which has since become part of JCVI) and the world of nonprofit genomic research. He established his J. Craig Venter Institute in 2006, funding it with money from his Celera stock holdings (local students and parents might be familiar with JCVI’s DiscoverGenomics! mobile science lab, which visits Washington area schools). About that time, he and Smith founded their privately held company, Synthetic Genomics, with business partners Juan Enriquez and David Kiernan. The institute currently has an annual operating budget of $65 million and receives 68 percent of its funding from federal grants. Synthetic Genomics, valued at $550 million in 2010, is one of a number of synthetic biology start-ups working to develop processes for making fuels, drugs and edible oils.
JCVI’s Rockville headquarters occupies a four-story, rented laboratory building in a science and technology park near Shady Grove Adventist Hospital. One floor holds row after row of floor-to-ceiling computers connected by tangles of colored wires, providing a dizzying data storage capacity of 500 terabytes to hold the huge and ever-growing trove of gene sequences generated by Venter’s research groups. Other floors contain offices and research labs. The scientists are a casually dressed, hip-looking crowd, most appearing to be in their 20s or 30s.
Venter maintains that the work environment is radically different from that of a government or university laboratory. “We don’t have tenure,” he says. As a condition of continued employment, he expects “an incredible level of productivity. ... We try to have the measurement be: ‘What did you do to change the world today?’ ”
Researchers at Venter’s centers are sequencing the DNA of organisms living in the air of Manhattan, in deep-sea vents, on hospital doorknobs and in coal seams a mile underground. Nelson leads a group participating in an NIH effort to sequence all of the bacteria living in and on the human body. Other teams are focused on exploiting the natural talents of microbes, such as bacteria that can break down human waste in water while simultaneously producing electric current.
And in a major new commercial collaboration with pharmaceutical giant Novartis, Venter’s researchers are trying to make the DNA sequences needed to create flu vaccines from scratch, instead of starting with live viruses, which could speed vaccine production by as much as two months.
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But none of the accomplishments at Venter’s centers has generated as much attention as the announcement on May 20 last year that one of his labs had created so-called synthetic cells.
“This is the first self-replicating species we’ve had on the planet whose parent is a computer,” Venter told reporters at a news conference at the District’s Newseum. “It’s clearly a dual-use technology, and that requires immense responsibility for whoever’s using it. We are entering an exciting new era where we’re limited mostly by our imaginations.”
Coverage by the global media was intense, breathless and rife with cliches: “Pandora’s box,” “playing God,” “Frankenstein’s monster in a Petri dish.”
In fact, the cells themselves were not synthetic, only their DNA. Scientists constructed copies of a natural bacterium’s chromosome and transplanted them into a related bacterium. The synthetic chromosomes “booted up” the recipient cells, effectively turning them into a different species — technically a new one, because there were a few genetic differences between the synthetically made chromosomes and those of the bacterium whose genome had been copied.
Some differences happened accidentally, but scientists also deliberately built in what Venter calls “watermarks” — bits of non-functioning genetic code to mark the new microbes as lab-made. They included encrypted versions of the researchers’ initials and of literary quotations, including one by James Joyce: “To live, to err, to fall, to triumph, and to re-create life out of life.”
In December, the Presidential Commission for the Study of Bioethical Issues recommended the new science and the federal policies for regulating it be developed in tandem, to minimize potential risks to health and the environment. Although environmental organizations such as the Worldwatch Institute and the Environmental Defense Fund have described the use of living cells to make biofuels as promising, other groups argued that the commission should have called for stringent regulation of life forms made through synthetic biology. Critics expressed concerns about misuse of the new scientific techniques — for instance, to make disease-causing organisms — as well as the chance that accidental release of synthetic life forms could produce environmental damage.
“Each of these is going to be completely novel,” says Eric Hoffman, a biotechnology policy campaigner with Friends of the Earth. “As much as the industry says that these things aren’t going to get out, once you start working at a commercial scale, it’s going to be impossible to prevent them from escaping.”
Venter agrees that federal and private oversight will be needed, although he says it would be far easier for evildoers to use an existing microbe as a bioweapon than to create a new one. “The hardest thing to do scientifically, even imaginably, would be to create a new pathogen,” he says. He maintains that the environmental risks can be minimized by engineering protective features into synthetically altered cells. He plans to engineer suicide genes into his oil-producing algae cells, lest they escape their ponds and generate their own oil spills.
“I consider myself fundamentally more of an environmentalist than many of these environmental groups,” he says. “We have to come up with new sources of food, new sources of water, new sources of energy. Trying to ignore leading-edge science and technology as a means of getting there is an ostrich approach of burying your head in the sand.”
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If some observers are skeptical about Venter’s predictions for the future of synthetic biology, it’s partly because he and others were overly optimistic about how soon the sequencing of the human genome would lead to medical advances. In 2000, a New Yorker profile of Venter by science writer Richard Preston predicted that by about 2015, patients would be able to walk into their doctors’ offices carrying a copy of their personal genome on a wallet-size “smart card,” and the doctor would use it to prescribe treatments. Venter acknowledges that those forecasts were way off.
“It’s always hard to put timelines on things,” he says, adding that he has been surprised at how slowly science has progressed in interpreting the genome. He now guesses it will be at least another “10 to 20 years” before it becomes cost-effective for patients to have their genomes sequenced.
Today’s sequencers are 1,000 times faster than the ones used a decade ago but not precise enough for diagnoses. And although the cost has come down — from several hundred million dollars to sequence the first human genome to less than $10,000 to sequence an individual genome now — sequencing an individual’s genome is still too expensive for widespread medical use. More important, “there’s not a huge advantage for having your genome sequenced right now, because we don’t know enough biology to interpret it,” Venter adds.
In addition to designing new kinds of cells to solve global problems, Venter hopes that in searching for the “minimal cell,” his research team will make a breakthrough in our fundamental understanding of the way a cell’s genes work together to make it alive — feeding, growing, sensing, able to adapt and reproduce. Working opposite each other at a bench in one of the institute’s San Diego labs, two of Venter’s most eminent scientists, Smith and molecular biologist Clyde Hutchison, are taking the smallest, simplest bacterial cells known and experimenting with stripping out groups of genes, just to see what will happen.
“What is essential for life? What are the actual components that you can’t have a living cell without?” Venter asks. “We now have the tools to try to answer most of that.”
Meanwhile, Venter is planning his life’s next phase. Divorced from Fraser in 2005, he married his longtime publicist, Heather Kowalski, in 2008. Kowalski, who is in her 40s, is a friendly, unpretentious woman who shares Venter’s love of sailing. Venter says his bouts with depression are a thing of the past: “The science is working well. My family life is very nice. All those things make a big difference.”
When I join the couple in his office at Synthetic Genomics, at the end of a day spent touring Venter’s labs, they are discussing the anticipated delivery of his new BMW 1600 GTL motorcycle, and making plans to ride together from San Diego to the Grand Canyon. As a Christmas present from Heather, he recently spent three days at a formula racing school on the Monterey Peninsula.
Sometime soon, if he can arrange funding, he hopes to sail his yacht on a $3 million research voyage around Cape Horn and to discover more new life forms along the way.
“Science in my view is, and should be, fun,” Venter says. “A lot of people make it tedious. I don’t understand why. ... I’m constantly accused of trying to have the best of all worlds, and I plead, actually, guilty.”
Susan Okie, a regular contributor to the New England Journal of Medicine, is a former Post reporter and science editor. She is an assistant professor of family medicine at Georgetown University School of Medicine and a volunteer physician with Mobile Medical Care of Montgomery County. She can be reached at firstname.lastname@example.org.