The God of Small Things

Mapping the human genome wasn’t enough. Now Craig Venter is trying to create a microbe that will free us from our addiction to oil.

Back when Craig Venter was the bad boy of science, racing the U.S. government to sequence the human genome—and using some of his own DNA to do it—he kept his face clean-shaven, and often posed for photographs in suits or medical coats. With his high forehead, bald scalp, and laborato­ry pallor, he looked more like central casting’s idea of a respectable scientist than the self-promoting egomaniac that his enemies labeled him, or the surf bum and Vietnam medic that, as journalists never failed to point out, he had been as a younger man.

These days Venter has the air of a richer, less-rumpled Steve Zissou, the Jacques Cousteau–like oceanographer played by Bill Murray in The Life Aquatic. He sports a wraparound white beard and has the persistent tan of someone who’s spent much of the past few years at sea, having circumnavigated the globe on a yacht called the Sorcerer II. His office, tucked away amid the sprawl northwest of Washington, D.C., seems to boast a model ship for every distinguished-scientist citation, and screens on the walls display a rotating series of photos from his voyage—deep-sea creatures alternating with shots of a windblown Venter at the helm. When a writer for Wired caught up with him somewhere in the South Pacific, Venter was wandering a beach naked, fishing items of interest out of the water. (“You’re glad I was clothed today,” he joked when I arrived for an interview last fall.)

Not that Venter has settled into retirement. The voy­age may have helped him relax and blow off steam after several years in the eye of a scientific, political, and media hurricane. But it was primarily a Magellan-meets-Darwin expedition in which Venter and his crew sifted the sea for enough biological material to map the genome of, well, the entire planet Earth, collecting millions of microbes on filter paper and shipping them back to Rockville, Maryland, for analysis. Venter’s labs once broke apart human DNA and put it back together again; now they’re attempting the same thing with microbial genes.

But this time, Venter is out to build new genomes, not just to analyze existing ones. He’s not just trying to understand how life works; he’s trying to make it work for him, and us. The race to map the human genome, in its headier moments, promised cures for Parkinson’s, Alzheimer’s, cancer. Venter’s current undertaking shows promise for something no less ambitious: a cure for our dependence on oil.

This is how you know that the quest for alternative energy is enjoying a moment in the sun: A Republican president with an oil-company background is talking up alternative fuels and has announced, in his State of the Union address, that America is “addicted to oil.” The energy companies themselves—BP and Chevron, for instance—are investing hundreds of millions of dollars in renewable-energy research. And a host of high-profile investors, from Richard Branson to Bill Gates, are jumping into the alternative-energy market as well.

We’ve been here before, of course. Since the 1970s, researchers have experimented with hybrid electric cars, cold fusion, wind power, solar power, geothermal energy, and hydrogen, all to little avail. Blame insufficient government investment, blame low gas prices, blame our obsession with SUVs, blame the not-in-my-backyard backlash against wind farms and nuclear-power plants—whatever you blame, all our turbines and Toyota Priuses haven’t kept America’s consumption of oil from skyrocketing.

But maybe this time is different. The scientific consensus on global warming and the role of carbon-dioxide emissions in heating up the Earth is stronger than it’s ever been. Concern is growing that the world might be nearing “peak oil”—the moment at which supply starts to decline (leading, some say, to the collapse of industrial civilization). And after 9/11 and the invasion of Iraq, just about everyone, from the most left-leaning environmentalist to the most hawkish neoconservative, thinks that for national-security reasons alone, the United States should be importing less crude from the Middle East.

Ironically, though, the most-talked-up oil alternative in this alternative-energy moment is a fuel that’s long been called a boondoggle: ethanol, a form of alcohol produced through the fermentation of sugar derived from plant matter, usually corn kernels. The federal government has been boosting ethanol since the 1970s: refiners who add ethanol to their gasoline get a tax break of 51 cents a gallon, and high tariffs help keep out competition from abroad. But thirty years and billions of dollars later, we have little to show for it beyond a raft of prosperous agribusinesses and a small network of gas stations, mostly scattered around the Midwest, that offer ethanol-compounded gasoline.

Like most alternative fuels, ethanol has problems on both the demand and supply sides of the equation. Fuels that consist primarily of ethanol—like E85, which contains only 15 percent gasoline—cost about as much as regular gas, and deliver fewer miles per gallon. If demand were high for such a fuel, there wouldn’t be enough to go around. The industry is currently capable of producing about 4.8 billion gallons of ethanol a year; the United States consumes roughly 140 billion gallons of gasoline annually.

So why the excitement over ethanol? The answer isn’t in corn kernels, but in the stalks, roots, and leaves of corn and other plants—“cellulosic” material that’s historically been difficult to break down into sugars efficiently, but that now might be only a few breakthroughs away from becoming the source that makes ethanol available on the cheap. Cellulosic ethanol could be made from agricultural waste, so that we need not rob our food supply for our energy supply. Better still, it could be derived from non-food- producing plants grown on land otherwise unsuitable for cultivation. Cellulosic ethanol wouldn’t provide a complete solution to our energy problem, but even many skeptics acknowledge its promise, and the Department of Energy is excited enough to have made the pursuit of cellulosic ethanol a key component of its plan to replace a third of annual U.S. oil consumption with biofuels by 2030.

All that’s needed is the right science.

This is where Craig Venter comes in—though arguably, he’s been there all along. Genomic research, after all, doesn’t just offer scientists an opportunity to take apart the genome of a human being, a mouse, or a bacterium to see how it works and what it does. It offers them a chance—if they’re sufficiently ambitious, or hubristic—to change what a genome does, and to make the organism do what we want it to do. And one of the obvious things we might want organisms to do for us—they already do it for their own purposes—is produce energy.

Venter took a roundabout route to scientific prominence. After growing up in a working-class neighborhood in the San Francisco area, he drifted through junior college, spending most of his time on boats and surfboards, and then enlisted in the Navy to avoid being drafted. It was the mid-1960s, and after training as a medic in San Diego—and being court-martialed for refusing a direct order from a superior officer, a woman he happened to be dating at the time—he was sent to Vietnam, where he spent a year in a field hospital in Da Nang at the time of the Tet offensive.

For the first six months, he worked in the emergency room. A thousand soldiers died around him; a rocket tore through his sleeping quarters. He contemplated suicide, and one day, as he later told the journalist James Shreeve, he started swimming out to sea, planning to paddle until exhaustion carried him under. Partway out he thought, “What the fuck am I doing?” and decided to swim back and live instead.

After surviving Vietnam—after choosing to survive it—Venter never drifted again. The brashness remained, and the surfer’s disrespect for authority, but they were channeled into a fierce ambition and a desire to make a difference in the world. He got married, went back to community college, and then enrolled in the University of California, San Diego, where he earned a joint doctorate in physiology and pharmacology, choosing research over medicine. (“A doctor can save maybe a few hundred lives in a lifetime,” he told his brother at the time, with a characteristic mix of ego and idealism; “a researcher can save the whole world.”) All this took six years. It was followed by a junior faculty position at the State University of New York, Buffalo, where he drove a baby-blue Mercedes, favored garish shirts and bell-bottoms, split up with his wife, and married one of his students, Claire Fraser. In 1984 he took a position at the National Institutes of Health. There he would first impress and then clash with James Watson, the famous (and famously contentious) co-discoverer of the molecular structure of DNA, who took over the leadership of NIH’s branch of the nascent Human Genome Project in 1990. After Venter developed a quick-and-dirty method of identifying genes, Watson, with Venter present, told a 1991 Senate meeting that the technique “isn’t science,” because the machines “could be run by monkeys.”

By the following summer, Venter had quit NIH and raised enough venture capital to found the Institute for Genomic Research, or TIGR, where he would have complete control of all research, although any marketable discoveries would belong to the commercial wing of the enterprise, a company called Human Genome Sciences; this was his initial step onto the nonprofit/for-profit tightrope he has walked ever since. In 1995, his team published the decoded genetic script for the bacterium Haemophilus influenzae; it was the first time the complete genome of a living organism had been mapped. Later that year, a team led by Fraser published the genome for the parasite Mycoplasma genitalium, a far simpler organism, with only about 500 genes to H. influenzae’s 1,800. “We immediately began to ask obvious questions,” Venter says. “Is there a minimal operating system for a cell? … Was [M. genitalium] the minimum, or could we eliminate genes from that species and get smaller?”

So began the quest for the “minimal genome,” the bare-bones genetic material necessary for life to sustain itself and reproduce. This required dismantling M. genitalium, which suggested another possibility: If you could take a genome apart bit by bit, why not put one together in the same way, creating “life from scratch,” as Venter puts it, with a genome of your choice? Meanwhile, Venter sequenced a third microbe, Methanococcus jannaschii, an organism found deep in the Pacific Ocean. M.jannaschii is an autotroph, meaning that it generates all its energy from inorganic substances. It survives by converting carbon dioxide and hydrogen to methane, and fixes the carbon from the carbon dioxide into its cellular protein structures—a process of obvious interest in a world with an excess of carbon dioxide. “That organism,” Venter says, was responsible for “stimulating our thinking, or my thinking, on the energy front.”

But then the human genome beckoned. In 1998, the biotech firm Perkin-Elmer persuaded Venter to head a new company that would use a technique called “whole-genome shotgunning” to try to speed up the genome-mapping process. At that point the government’s Human Genome Project, using a slower, more painstaking method, was seven years away from its projected date of completion. The new company, eventually called Celera, vowed to finish the work in three years. The pledge, and the race that followed, made Venter world-famous. It also cemented the reputation for egomania that he had developed at SUNY Buffalo, at NIH, and among his partners at Human Genome Sciences (with whom he feuded and eventually parted ways), and it added a multitude of government scientists and officials to an already-substantial list of enemies.

The Human Genome Project’s custodians would probably have resented any private-sector rival, but Venter made himself easy to loathe. In May of 1998, when he met with HGP scientists to outline his company’s plans, he suggested that while his team polished off the human genome, they might consider turning their attention to another creature. Specifically, the mouse. (After that meeting, Watson, who had left the project in 1992, gave the HGP scientists his view of Venter. “He’s Hitler,” Watson said. “This should not be Munich.”)

Venter’s rivals in the government predicted that his method would deliver a patchy, error-ridden product, and warned that if he succeeded in sequencing the genome first, Celera could enjoy a dangerous monopoly over information that rightly belonged in the public domain. They were wrong on both counts, in part because the Human Genome Project, spurred on by the competition, finished at about the same time as Celera. A tie was announced in June of 2000; shortly thereafter Celera’s stock collapsed, and Venter was forced to resign as president.

He had money, though, from stock in various companies, and he had freedom: “Having sequenced the human genome,” he says with a laugh, “gives you a few options.” Using $100 million of his own funds, he started three not-for-profit research centers, which are now consolidated under the J. Craig Venter Institute. The institute is based in the same Rockville headquarters as TIGR—a miniature campus, with three low buildings roofed in Spanish tile, interspersed with ponds and greenery, and a taller building whose exterior panels are colored red and green, blue and yellow, to represent the four nucleotides (adenine, cytosine, guanine, and thymine) that bind together the DNA double helix and make up the code of life. One of the new centers, the Institute for Biological Energy Alternatives, took up the challenge of creating the minimal genome. Because a minimal genome has no nonessential pathways, it is the ideal template for the creation of designer organisms. By inserting “cassettes” of carefully engineered genes into a stripped-down genome, Venter hoped to construct organisms that would do exactly what he wanted, and nothing else—organisms, for instance, that could serve as “biofactories,” carrying out energy-generating functions that had been written into their genetic code.

In 2003 the IBEA team, led by Hamilton “Ham” Smith, Venter’s longtime research colleague and the winner of a 1978 Nobel Prize in Medicine, took just fourteen days to reconstruct the 5,386 nucleotide base pairs of a virus called phi-X174, which attacks certain bacteria. A virus is far short of a bacterium, the real goal, which would have hundreds of thousands of base pairs. (Viruses have no metabolic processes of their own, and scientists debate whether they even count as living organisms.) But this achievement prompted Venter to step back into the for-profit world, and in the summer of 2005 he founded Synthetic Genomics, a company that would build on the minimal-genome research. Meanwhile, he was making his ocean-sifting trip on the Sorcerer II. The first third of the material from the voyage (the rest is still being sequenced) has yielded 6 million genes. Somewhere in this wealth of material, perhaps, are the keys to better living through ethanol—the genes that, inserted into a minimal genome, could produce an organism able to break down cellulose quickly and cheaply.

Or at least that’s one possibility. Aristides Patrinos, Synthetic Genomics’ president (Venter is the CEO), calls the cheap, efficient creation of cellulosic ethanol “the holy grail,” and he should know, having been in the alternative-energy field since the 1970s. Hiring Patrinos was a coup for Venter and a sign that Synthetic Genomics intended to be a major player. Patrinos had been one of the government’s point men for alternative energy, while serving as the associate director for biological and environmental research at the Department of Energy from 1995 until last year; he was responsible for getting references to alternative energy into the 2006 State of the Union address, and he succeeded in boosting federal funding for biofuel even as belts were tightening elsewhere in Washington. A wiry, mustachioed man who seems in danger of being swallowed by his clothes, Patrinos has been friends with Venter since the early 1990s, and he supplied the IBEA with government funding in the early ’00s, before Venter lured him into the private sector.

Synthetic Genomics is still getting off the ground: when I visited Patrinos, in October, the movers were bringing furniture to its Rockville offices, two parking lots over from Venter’s main campus, and half the space was empty, awaiting new hires. The company has quietly approached a number of energy companies for funding. It is using the capital raised so far to support minimal-genome research at the Venter Institute, and it has laboratories in La Jolla, California, where most of its scientists will be based.

Meanwhile, through the institute, Venter has teamed up with the University of California, San Diego, and Iowa State University to compete for $500 million in funding from BP, which has pledged to establish a biofuel research laboratory at an American or British university. Venter and the two universities have also joined forces to compete for one of the $125 million grants that the U.S. Department of Energy will award to each of two winning proposals for bioenergy research centers.

Such labs are the places where the rubber will meet the road—or, to quote Energy Secretary Samuel Bodman, where “the right microbe” will meet “the right biomass source.” Bodman is an enthusiast: he envisions making cellulosic ethanol cost-competitive with gasoline by 2012, and he said in a recent speech that the research centers have “the potential to be the best thing we do during my tenure as energy secretary.”

The word potential is, of course, key. You can turn cellulosic biomass into ethanol in the lab, but nobody’s done it on an industrial scale, and with today’s technology, cellulosic ethanol can cost twice as much to make as its corn-based cousin. So everyone is looking for greater efficiency. Iogen, a Canadian corporation that’s currently building one of the first “biorefineries” for cellulosic ethanol, is working on using genetically modified yeast to make fermentation more efficient. Dyadic, a Florida-based biotech company, has been modifying fungi found in the Russian Far East and hopes to produce commercial quantities of an enzyme that breaks down cellulose. Ceres, a California plant-genetics company, is trying to create ideal “energy crops,” plants that are hardier and more drought-resistant than your average weed and can be broken down quickly.

All of these avenues, though, are fairly complex. Synthetic Genomics’ vision, Patrinos has said, is of the simplest process imaginable: engineered microbes that could transform the crops-to-biofuel process into a one-step stew.

When I spoke with Venter, as an early-autumn rain churned up the ponds on his campus, he was already looking beyond ethanol. It may well be that a gene from the ocean, or elsewhere, will enable a synthetic organism to break down cellulose quickly and cheaply—but that’s only the first step to real independence from oil.

“Ethanol’s not an ideal fuel,” Venter pointed out. In the long run, you want fuels that burn hotter and that don’t require long-distance transportation, vast tracts of land, and huge biorefineries. Fuels, perhaps, that you could make at home. (“Everybody would have their own little bath in their backyard and fuel their car from it.”) Natural gas from sewage sludge. (“Pretty bad-smelling stuff coming out of septic tanks. If you could convert it into something useful and burn it … methane is natural gas, you know?”) And hydrogen, the cleanest fuel of all, from sunlight. (“We’re working on modifying photosynthesis to go directly from sunlight into hydrogen production.”)

All of this is speculative, of course. “Sometime in the future,” Venter says, “I am a hundred percent certain scientists will sit down at a computer terminal, design what they want the organism to do, and build it.” When is “sometime in the future”? He doesn’t say, but he is willing to venture that we should expect biological research to spark large-scale changes in the energy scene within the next ten years. The prediction comes with a touch of disarmingly frank self-centeredness: “Ham is in his mid-seventies. I’m turning sixty. We don’t want something with a fifty-year timeline. We’re egocentric, we want to see it take place, so we’re determined to have it take place in the next decade.”

And maybe it will. But research needs steady support, and investors tend to move in cycles. The 1970s saw great enthusiasm for “synfuels,” or synthetic substitutes for oil and natural gas; however, the enthusiasm and the funding dried up in the ’80s, once gas prices plunged back to earth from their oil-crisis high. Similarly, this past fall, as the cost of gasoline dropped, the stock market’s excitement about ethanol firms diminished as well. Consequently, Venter believes, the government needs to make a steady commitment to alternative energy. But not with props like the 51-cents-a-gallon ethanol subsidy. The government should be funding research rather than actual products, he argues, so as not to create “a false industry that collapses once the subsidies collapse.” And not with the sort of large-scale, Manhattan Project–style effort that many pundits have called for. If you put everyone into a laboratory in New Mexico or Nevada and tell them to come up with a solution, Venter says, it will just be the Human Genome Project all over again: a slow-motion process waiting for the kind of private-sector kick in the pants that he provided. Instead, Venter wants to see the government fund a variety of competing companies and research projects. “I’d rather see a thousand points of light than one dull bureaucracy,” he says. “We don’t have to have a single industrial-complex solution to this problem.”

A thousand points of light. A thousand Craig Venters. It’s a very American image, and for a man with a reputation for an outsized ego, it has a surprising humility about it—the Venter idealism breaking through the Venter arrogance. “I’m hoping our research teams come up with the breakthroughs,” he says, “but I think as a society, we need those breakthroughs, and there’s no guarantee we’ll make them. So … I’d be almost as happy if somebody else makes those breakthroughs.”

Almost.