# News this Week

Science  29 Nov 2002:
Vol. 298, Issue 5599, pp. 1694
1. HUMAN GENOME PROJECT

# Genome Institute Wrestles Mightily With Its Future

1. Elizabeth Pennisi

WARRENTON, VIRGINIA—The job is finally done. After more than a decade, the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, is about to finish determining the order of the 3.1 billion bases that make up the human genome. Now, NHGRI needs to figure out what to do next, and that's proving not to be an easy task.

Since 1990, NHGRI's budget has ballooned from $60 million a year to$429 million in 2002, the majority of that going to its flagship enterprise, the Human Genome Project. With the human genome practically finished, “it's more challenging to convince Congress and the public [that] this is not the end of the road but the beginning,” says Elias Zerhouni, director of the National Institutes of Health (NIH), NHGRI's parent institution.

After a year of struggling to craft a new mission for itself, NHGRI unveiled a draft plan for its future last week at a meeting here. The initial response of the audience—some 100 biologists, bioinformaticists, social scientists, and policy-makers—was tepid at best. The plan “kind of read like an organizational identity crisis,” says Elliott Sigal of Bristol-Myers Squibb in Princeton, New Jersey. Like many others, he said that the institute needed to be clearer in what it wanted to accomplish.

The revamped NHGRI would continue to apply genomics to biological research—collecting genome sequence, assessing gene function, for example, and developing technologies and databases to enable other researchers to do the same. On the social front, the institute would strengthen its efforts to prevent genetic discrimination, for instance, and to work with companies to ensure academic access to genomic data. But in a major departure from the past, NHGRI would get more directly involved in medical research and education and even set up its own clinical studies.

One of the concerns about this ambitious plan is that it lacks the concrete goals that have been the hallmark of past proposals. Five-year plans issued in 1993 and 1998 contained specific milestones: a physical map with markers every 100,000 bases, a draft of the human genome by 2001, and so on. And that's the type of fixed timeline that many expected of the 2003 plan. Instead, this draft seems “squishy,” or “fuzzy,” with projects that seem to stretch indefinitely into the future, says Richard Gibbs, director of the Baylor College of Medicine's Human Genome Sequencing Center in Houston, Texas.

NHGRI did make some specific promises, such as finishing 45 to 60 gigabases of sequence by 2008. That's the equivalent of about 18 mammalian genomes and will likely include fungi, the chimpanzee, the cow, and other organisms recently designated as high priorities (Science, 31 May, p. 1589).

But the goals became more vague—and the participants more uneasy—when NHGRI said it also wanted to define the function of all the parts, such as genes and regulatory elements, of the human and other genomes, a task that could take many years. The reviewers had trouble even agreeing on what constituted a “part” or how far NHGRI would be expected to go in determining function. “If NHGRI is not clear about this, then [it's] going to get accused of overreaching,” says Thomas Pollard of Yale University in New Haven, Connecticut.

NHGRI director Francis Collins explained that this was not just a 5-year plan but a vision of the future, one that would guide efforts into the early 21st century. “It [was] meant to inspire NHGRI and its constituencies, NIH and the public,” says Richard Lifton of Yale, a member of the NHGRI advisory committee. But almost everyone agreed that, as written, it fell short of that goal.

The most controversial part of the draft plan is NHGRI's proposed foray into clinical medicine. Collins thinks his institute is well poised to pioneer new approaches to health, such as studying genes in people who don't get sick even though many of their relatives suffer from, say, heart disease. In addition, NHGRI would like to play a leading role in establishing a long-term study of the health of several hundred thousand people, in part to track links between genetic variation and disease. Without this large group of people, the HapMap, a major undertaking to map variation in stretches of human DNA called haplotypes, will be of limited use, says Lifton.

However, some were troubled by the logistics of NHGRI starting its own clinical studies. “I would hate to see this institute get bogged down” in recruiting participants, says Gerard Schellenberg of the Veterans Affairs Medical Center in Seattle, Washington. Others wondered how NHGRI would muster the epidemiological and clinical expertise needed for these efforts.

Less ambitious projects fared better. There was much support, for instance, for NHGRI investing more in helping to find genes in single-gene disorders. And all agreed that NHGRI needs to figure out ways to get physicians and medical schools to take advantage of what genomics could offer in terms of diagnosis, understanding disease mechanisms, and, eventually, treatments. “This is an enormous problem,” says Robert Tepper, chief scientific officer at Millennium Pharmaceuticals Inc. in Cambridge, Massachusetts.

After a harrowing 2 days, Collins conceded that “we have our work cut out for us” in revising the plan—again. The draft circulated last week had already undergone multiple revisions, he says; to get this far, he and his staff hosted an information-gathering meeting last year and, since then, about a dozen workshops on specific topics, such as proteomics and genetic variation.

Several of Collins's colleagues were worried that he might be discouraged by the “vigorous” feedback, asking Collins midway through, “Are you OK?” But for Collins, such debates are not new. His sense was that, overall, the group was enthusiastic about NHGRI's new directions. And as for the tough critique, he says, “This is how the genome community operates.”

2. MARINE ECOLOGY

# Scientists Brace for Bad Tidings After Spill

1. John Bohannon,
2. Xavier Bosch,
3. Jay Withgott*
1. Freelance writers John Bohannon reported from Vigo, Xavier Bosch from Barcelona, and Jay Withgott from San Francisco.

VIGO, SPAIN—From a distance, the rocky beaches of Galicia, Spain's northwestern province, look as if they're slathered with chocolate mousse. The illusion dissolves with the first whiff of petroleum, a reek stronger than that at any gas station. Fighting the stench, Peregrino Cambeiro, a technician with the Higher Research Council's Institute of Marine Research in Vigo, shovels sludge (a mixture of seawater and petroleum solids that resembles molasses to the touch) into plastic buckets, then loads them onto a flatbed truck. These are the first samples of the spill that will be brought back to the institute for analysis so that researchers can figure out what sort of oil they are dealing with and assess what impact it will have on marine and other life.

It has been a week since the hull of the tanker Prestige first tore open and began disgorging a cargo of fuel oil off the Spanish coast. Every day, more sludge washes ashore, driven by gusts of wind that top 100 kilometers an hour. On 19 November, fearsome, wind-whipped waves overwhelmed the stricken tanker, which ripped in half and sank. So far, 10,000 tons of oil are known to have leaked. The challenge for scientists is to predict what will happen to another 67,000 tons that went down with the ship and how it might harm life on the seabed. “There's still another shoe to drop here,” says David Kennedy, director of the U.S. National Oceanic and Atmospheric Administration's oil-spill response program. “The size of that shoe is hard to determine, but history shows there's more to come.”

Back in Vigo, Cambeiro unloads the sludge and wearily strips off his slime-covered overalls. Crown Resources, the oil trading firm based in Switzerland that chartered the Prestige, has stated that the ship was carrying bunker oil, a viscous mix of different grades of petroleum used by ships and power plants. Ricardo Prego, an environmental chemist at the Vigo institute, will use Cambeiro's samples to determine the oil's precise composition. While Prego probes the sludge's chemistry, institute director Antonio Figueras will test its lethality in a range of life forms, including bacteria, fish, and human cells. “This is a crude measure,” says Figueras, who will also look for sublethal effects, such as how the sludge affects the immune system and reproduction.

The Spanish government is waiting anxiously for the results of the analyses, which will come in over the next several weeks. On 18 November, it slapped a ban on fishing and shellfish harvesting along 300 kilometers of spoiled coastline. Aquaculture of bivalves such as blue mussels is Galicia's largest industry and is second only to China in annual harvest. It's also the industry that's most vulnerable to the sludge, which smothers filter feeders. The bulk of the bunker oil spilled so far has swung north of the key estuaries where mussels are cultured. But until it can be proven that the seafood is safe to eat, more than 5000 Galician fishers and aquaculturists will be out of work.

Other forms of wildlife are, as expected, taking a huge hit. Jesús Domínguez, an ornithologist at the University of Santiago de Compostela, says the spill could have devastating effects on several species of endangered birds that winter along the Galician coast, including the last 15 to 20 breeding pairs of the common murre in the region. “We can expect a substantial impact on birds,” says Malcolm Spaulding, a marine environment modeler at the University of Rhode Island, Narragansett. “They're in for a sticky mess.”

Spain's environment minister, Jaume Matas, predicts that 1.5 million square meters of beach will have to be cleaned by hand. The cleanup and direct economic losses will likely top $145 million. (The European Union has pledged$115 million in assistance.) Many scientists blame politicians for the disaster's scale. The French, Spanish, and Portuguese governments all refused to allow the leaking tanker into their ports, and Spain even considered bombing it with F-18 fighters to incinerate the fuel. “The Spanish government has shown an evident incapacity to manage the crisis,” fumes Domínguez. “We think we can dump anything we want, and it will just go away,” says Figueras. “But it will come back to haunt us.”

Mariano Rajoy, Spain's vice president, has asserted that the tanker's disappearance beneath the waves averted a much larger disaster because the high pressure and low temperature (3°C) at 3600 meters, where the wreck is said to lie, will solidify any fuel oil left inside the hull. But Richard Steiner, a marine conservation biologist at the University of Alaska, Fairbanks, who studied the 1989 Exxon Valdez oil spill, says that to believe the sunken oil will remain stable is “more wishful thinking than reasoned expectation.” If the oil containers break, much of it could still reach the surface.

Even if the oil stays near the bottom, experts are split about its potential impact. “We really don't have much experience with this,” says marine chemist John Farrington of the Woods Hole Oceanographic Institution in Massachusetts. Steiner warns that toxic components in the water-soluble fraction of the fuel oil could ultimately cause “an enormous ecological shock.” Delayed effects from the Valdez spill included brain lesions, reproductive failure, and genetic damage in wildlife, he says, adding that more than 13 years after that spill, only a quarter of the injured populations has fully recovered. Others argue that the bunker oil, with fewer aromatic toxicants, will prove less poisonous to sea life than the Valdez crude spilled in Prince William Sound. The impact offshore, offers Spaulding, “is not likely to be large.” The Vigo institute's chemical analyses of the spill should help refine such predictions.

On 22 November, Spain dispatched a submarine to examine the Prestige's condition and the extent of damage to the seabed. Scientists also would like to see an expedition with a remotely operated vehicle that uses sonar to create a bathymetric map of the ship and the surrounding area. “It's not cheap,” says oceanographer Larry Mayer of the University of New Hampshire, Durham, “but there are important things at stake.” That's a sentiment with which most Galicians would agree.

# Senators Take Aim at Texas Project

1. David Malakoff

Texas A&M University found itself the villain of a political drama last week, as the U.S. Senate rushed to complete work on legislation creating the new Department of Homeland Security (DHS). It would have much preferred a backstage role.

The Senate, meeting in a lame-duck session after the 5 November election, was trying to pass a 450-page bill creating the new department. Some senators complained that the version passed by the House of Representatives was larded with favors to special interests. The worst, they said, was one shielding vaccinemakers from lawsuits. But included on their seven-item hit list was a clause setting out 15 criteria for selecting at least one university-based center to conduct security research and training.

Critics charged that the criteria, crafted last summer by Texas lawmakers allied with A&M, undermined the concept of basing government research awards on open, peer-reviewed competition (Science, 9 August, p. 912). For example, the clause required eligible schools to be affiliated with a U.S. Department of Agriculture “training center” and to show “demonstrated expertise” in wastewater operations and port security. Texas A&M fit the bill, but most public and private research universities do not. “This is nothing short of ‘science pork,’” said Senator Joseph Lieberman (D-CT), who led efforts to delete the provision.

A&M advocates insist that the language was intended only to make sure that the center was based at a university with the proper breadth of experience in addressing security issues. They note that several potential competitors, including the University of California and the State University of New York systems, had no problem with the language. And the new department retains the right to use peer reviewers, they add. “There has been a great deal of misinformation,” says Larry Meyers, a Washington-based lobbyist for the university.

To strip out the language, Lieberman needed the support of three moderate Republicans who had expressed concerns: Senators Olympia Snowe (ME), Susan Collins (ME), and Lincoln Chafee (RI). However, the trio was under heavy White House pressure not to amend, and thus delay, the DHS bill. Republican leaders won their support by pledging to alter three provisions, including the university and vaccine language, when the new Congress convenes in January.

To seal the deal, Snowe and Collins stood in a cloakroom off the Senate floor with GOP chief Trent Lott (R-MS) as he telephoned House leaders (one of them en route to Turkey) to obtain their agreement to amend the bill next year. Snowe, Collins, and Chafee then voted against Lieberman's amendment, ensuring its defeat and clearing the way for Senate approval of the entire bill.

“It was pretty amazing to see an academic earmark become a make-or-break issue on such high-profile legislation,” says one university lobbyist. The A&M language, observers say, became a lightning rod for Democrats out to embarrass House Republican leader Tom DeLay, a Texan closely associated with the proposal, and for Republicans who were angry that their states might be frozen out.

Despite the setback, Texas A&M says it is ready to compete for the center. And congressional aides note that DeLay and other Texas lawmakers could still earmark money for the project in a spending bill. Says one Republican staffer: “The idea that this is going away is absurd.” Adds another aide, who is opposed to the project, “This is like a horror movie: The creature takes a licking but somehow keeps on ticking.”

4. ASTRONOMY

# X-rays Show a Galaxy Can Have Two Hearts

1. Alexander Hellemans*
1. Alexander Hellemans is a writer in Naples.

Astronomers have sighted evidence of two black holes spiraling toward an eventual collision in the center of a nearby galaxy. The discovery—made by an international team of astronomers using data from the orbiting Chandra X-ray Observatory—has confirmed astronomers' long-held suspicions, based on indirect evidence, that the black holes at the hearts of many galaxies might come in pairs.

“It was not a surprise. … We have been thinking about it for more than 20 years,” says Astronomer Royal Martin Rees of the University of Cambridge, U.K. In 1980, Rees, together with Mitchell Begelman of the University of California, Berkeley, and Roger Blandford of the California Institute of Technology in Pasadena, proposed that the waltz of binary supermassive black holes at the centers of some galaxies explains why jets of energy spewing from the galaxies sometimes wander, or precess. But their ideas have remained speculative until now.

The galaxy that harbors the double black hole NGC 6240 lies 400 million light-years from Earth. “Ever since its discovery, it has received a lot of attention,” says team member Stefanie Komossa, an astronomer at the Max Planck Institute for Extraterrestrial Physics in Garching, Germany. In 1983, astronomers observing NGC 6240 in visual light found that its shape is strongly distorted—an indication that it consists of two galaxies that have collided. What really piqued their curiosity, however, was that the galaxy radiated enormous amounts of power at longer wavelengths, in the infrared part of the spectrum.

Astronomers knew of only two mechanisms that might explain such huge infrared emissions. NGC 6240 might be alive with starbursts, swarms of newly forming stars. Alternatively, like many other galaxies, it might contain an active galactic nucleus (AGN): an enormous engine that blasts out x-rays as matter falls toward a black hole in the galaxy's center. Dust clouds near the core of the galaxy would absorb x-rays and reradiate the energy in the infrared.

When Chandra was launched in 1999, its high-resolution x-ray imaging made NGC 6240 an obvious target, Komossa says. She and her colleagues set out to find the galaxy's x-ray powerhouse. Earlier observations by the ROSAT x-ray observatory, which Germany, the U.K., and the U.S. operated during the 1990s, had hinted that the galaxy's central x-ray source was oblong rather than spherical. In 10 hours of observations made in July 2001, Komossa's team found that the elongated source was actually two sources, thousands of light-years apart.

Several telltale signs show that the x-ray sources are black holes, Komossa says. First, they are very intense and concentrated, and they are emitting extremely high-energy x-rays—hallmarks of AGNs but not of starbursts. What's more, the spectrum of x-rays from the galaxy's center shows a strong emission line caused when cold, nonionized iron atoms absorb and release energy. Starbursts don't make iron fluoresce that way, but highly energetic x-rays from AGNs do.

The researchers estimate that each black hole has a mass between 10 million and 100 million times that of our sun. The distance between them, 3000 light-years, means that they must rotate around their common center over a period of millions of years. Over hundreds of millions of years, the two bodies will spiral toward each other, giving off energy in the form of gravitational waves, and ultimately merge. Such mergers might explain why some galaxies don't show an increased concentration of stars toward the center, Rees says: “In the process of merging, the binary would have kicked out the stars from the center.”

Gravitational waves unleashed by similar mergers should be detectable by the Laser Interferometer Space Antenna, a constellation of six spacecraft that the European Space Agency and NASA plan to launch later this decade (Science, 16 August, p. 1113). Because most galaxies are expected to contain supermassive black holes, and many galaxies merge, coalescent black holes might be common. “We may observe about one merger per year if we observe all the galaxies out to the limit of a big telescope,” Rees says.

5. PLANETARY ORIGINS

# A Quickie Birth for Jupiters and Saturns

1. Richard A. Kerr

Talk about a major embarrassment for planetary scientists. There, blazing away in the late evening sky, are Jupiter and Saturn—the gas giants that account for 93% of the solar system's planetary mass—and no one has a satisfying explanation of how they were made. Of course, they formed from the infinitely more diffuse gas and dust of the solar nebula as the sun formed. But what could entice that much gas to condense into planets before it all dispersed in a million years or so?

On page 1756, a group of astrophysicists presents computer simulations of the nascent solar system that suggest a possible mechanism: runaway fluctuations in the disk's density. In their model, gas giants of about the right size, number, and orbit condense from a disk of gas to look like very young Jupiters. The trick was to simulate the process in fine detail so that the gas's own gravity could take over. “It's a beautiful calculation,” says astrophysicist Richard Durisen of Indiana University, Bloomington. “It's a step along the way, but this is not the final answer.” A next step is to work out whether some disruptive forces not yet included in this model might frustrate the disk's gravitational urge to collapse on itself and spawn planets.

Until recently, theorists assumed that, for a gas giant to form, a small core of rock with the mass of perhaps 10 Earths must accumulate bit by bit as kilometer-size planetesimals collide with one another. Only then would the core have the gravitational heft to begin pulling in the gas that would make up 99% of the planet. But in the meantime, the spinning protoplanetary disk is dispersing quickly. By current estimates, it's gone before a Saturn can grow, much less a Jupiter. But the alternative to accretion is even less appealing: Depend on a patch of slightly denser gas forming—perhaps through random fluctuations—that is massive enough to pull in more gas, which could then pull in even more gas, leading to a runaway collapse into a planet. Such a gravitational instability mechanism had long appeared to require a disk 10 times as massive as expected. In 1998, astrophysicist Alan Boss of the Carnegie Institution of Washington revived gravitational instability by simulating gas clumping in a disk of reasonable mass, but he couldn't show that the growing clumps would survive to become planets.

Astrophysicists Lucio Mayer and Thomas Quinn of the University of Washington, Seattle, and their colleagues decided to throw more computing power at the gravitational instability problem. Using a model that they had previously built to study galaxy formation, they simulated a swirling gas disk with a million particles—10 times the number used in earlier efforts—orbiting a protosun. Run for several weeks on a massively parallel supercomputer, the model achieves an extra margin of realism, thanks to its inherent ability to automatically increase resolution where it counts the most: where mass is concentrating to form planets.

After just 1000 years of simulated time, the runaway process had produced planets: The model's disk had clumped, clumps had merged, and two or three planets had emerged that bore some resemblance to the 100-plus gas giants found so far around other stars. The simulated planets had masses of two to 12 times that of Jupiter, orbited at between three and 20 times Earth's distance from the sun, and moved in elongated orbits. But the model's planets showed little sign of moving inward, as many extrasolar planets have presumably done. Nor does the model help explain the rounded orbits found in one solar system—our own.

The new modeling “is a very important step forward for the disk-instability mechanism,” says Boss. “It shows that it is plausible that clumps could survive long enough to become gas giant protoplanets.” But not even Boss thinks that disk instability is home free. “One has to be a little cautious,” notes Durisen. Properly accounting for all the forces that work against gravity—including internal heating—must await future modeling, he says. Starting simulations with a realistic amount of instability is difficult, adds dynamicist Jack J. Lissauer of NASA's Ames Research Center in Mountain View, California; he thinks these runs started with far too much. And these simulations are “like a lab experiment that needs confirmation,” says Durisen. It seems the gas giants will be glaring down a while longer.

# Universities Promise More Tech Transfer

1. Wayne Kondro*
1. Wayne Kondro writes from Ottawa, Canada.

TORONTO—Canadian university administrators hope they haven't struck a Faustian bargain. In return for a promise by the government to double research funding and create a permanent fund to pay the overhead costs of conducting federally funded research, universities have agreed to do a better job of turning academic research into commercial products. The deal gives each side something it badly wants, at a price both sides appear willing to pay.

The terms of the quid pro quo were announced here last week, at the National Summit on Innovation and Learning. The event, held despite a nationwide snowstorm, gave more than 500 members of Canada's academic, business, and financial elite a chance to offer final comments on the government's ever-evolving blueprint for doubling federal research spending (Science, 15 February, p. 1211). The doubling would raise the R&D budget to $9.2 billion by 2010. Industry Minister Alan Rock says that the tradeoff, part of a proposed Framework Agreement on Federally Funded Research, marks the first time that academia has formally acknowledged its responsibility to generate economic wealth. “I wanted to commit them [academic institutions] in principle to a link between public funding and economic outcomes,” he says. At the core of the deal lies a government promise to roll a “one-time” allocation this year of$125 million for overhead costs associated with publicly funded research into some form of permanent funding program in next year's federal budget. The government also vowed to revive a promise to double outlays by 2010 for the three federal granting councils and to support training of more graduate students.

In return, the Association of Universities and Colleges of Canada (AUCC) agreed to “a doubling of the amount of research performed by universities and a tripling of commercialization performance” over the same period of time.

The parties must still iron out how to measure growth in academia's contribution to the economy. Canadian universities now lag well behind their U.S. counterparts on standard measures, such as licensing revenues, because of Canadian industry's reduced capacity to make use of new knowledge and technology, says Association of University Technology Managers president Janet Scholz of the University of Manitoba in Winnipeg (see graphic).

University leaders seem satisfied with both the terms and the overall symbolism of the arrangement. “Because we're starting a bit lower, tripling [of commercial activities] is realistic,” says Claude Lajeunesse, president of Ryerson University in Toronto. “It will require very, very strong commitment from researchers. But once they understand that this is not a threat to their freedom or their research and that, rather, it is something that will help them pursue new areas and, in a sense, be more relevant, then the vast majority will say this is good.”

“No doubt there will be a lot of discussion about the appropriate benchmarks” for measuring commercial performance, says AUCC vice chair Peter MacKinnon, president of the University of Saskatchewan in Saskatoon. “The amount of money spent, the amount of licenses that could be expected to result, patents, and start-ups: All of these things would be relevant.”

Several administrators note wryly that tripling commercialization output shouldn't prove too great a challenge, given that the current base is so low. They also don't anticipate the need to change current rules that generally assign intellectual property rights to individuals rather than the institution, as recommended by the national Advisory Council on Science and Technology (Science, 30 April 1999, p. 726).

The government won't penalize individual universities that fall short, Rock says, because the promise applies in the aggregate. But neither will it allocate funds to help universities hire or train staff to promote research findings to business. However, universities may choose to use a portion of the monies allocated for so-called indirect costs to promote commercialization.

Before the promise becomes reality, Rock must successfully negotiate with other government factions seeking massive hikes in funding to rejuvenate the national health care system, retool the military, and honor environmental commitments from Canada's embrace of the Kyoto protocols. But Rock believes that he will have an easy sell to his Cabinet colleagues. “How are we going to be able to afford all this? The answer, of course, is innovation,” he says. “If you innovate, if you increase productivity and competitiveness, your economy performs better, more people are employed, the revenues increase, and you're able to afford to do more.”

7. GENETICS

# Venter Gets Down to Life's Basics

1. Eliot Marshall

Never shy about his aims, DNA sequencer J. Craig Venter Jr. announced this week that he has won a government grant to design a novel form of life. The U.S. Department of Energy's science office has awarded his group $3 million over 3 years to “develop a synthetic chromosome,” the first step toward making a self-replicating organism with a completely artificial genome. Venter also announced that he has recruited molecular biologist Hamilton O. Smith, a 1978 Nobel laureate who has worked with him on many sequencing projects (including some for their ex-employer, Celera Genomics) to head up a 25-person scientific team at Venter's new outfit, the Institute for Biological Energy Alternatives in Rockville, Maryland. The purpose of the experiment, Venter says, is to develop an efficient but rigidly controlled organism that can carry out specific tasks, such as removing unwanted carbon or toxic materials from the environment or producing hydrogen for fuel. Several years ago, Venter, Smith, Clyde Hutchison, and others at The Institute for Genomic Research in Rockville began trimming a small organism's DNA to create a “minimal genome” that would still sustain metabolism and replicate. This team showed in 1999 how the minute genome of Mycoplasma genitalium might be truncated to about 300 essential genes and still reproduce (Science, 10 December 1999, p. 2165). Venter now wants to put his minimalist concept to the test: “We took a couple of years off to sequence the human genome” at Celera, he says, “and now we're back” working on the minimal genome. Others have modified existing organisms to carry out environmental tasks. But Venter says he wanted to start from scratch because “we don't want [an organism] that can adapt. We want something that's truly robust, but—if it got out of a specialized environment—we wouldn't want it to last 5 seconds.” He's also interested in the fundamental challenge of discovering the essential genes needed to support life: “That's the main reason we're doing it.” The project raises ethical challenges, however, as Venter acknowledges. Several years ago he commissioned a review headed by ethicist Mildred Cho of Stanford University to weigh the risks of creating new life forms. The panel concluded that there were no showstopping moral issues but recommended strongly that public authorities review the risks of environmental contamination and the possibility that this technology might be used in biological weapons. One member of that panel, bioethicist David Magnus of the University of Pennsylvania in Philadelphia, says that 1999 report (Science, 10 December 1999, p. 2087) was “prescient” in warning about bioweapons. “We ought to be talking about these risks now and developing the means to control the technology” if it works, says Magnus. The biggest obstacle, according to Hutchison, now at the University of North Carolina, Chapel Hill, will be fitting the minimal genome with a working cell structure. This, he says, will be “technically quite a challenge.” Indeed, even Venter acknowledges that it might prove impossible. But when it comes to evaluating Venter's implausible goals, Magnus advises: “Never bet against him.” 8. AGRICULTURE # Taking the Bite Out of Potato Blight 1. Glenn Garelik* 1. Glenn Garelik is a writer in Falls Church, Virginia. The mold that infested Ireland's potato fields in the 1840s has spread around the globe—and grown more aggressive than ever; researchers are working to contain it Even in Russia's relatively well-off St. Petersburg region, it's a rare household that can keep itself fed without a reliable supply of potatoes from the family plot. So the alarm level was high when people recognized symptoms of late blight on their staple crop last summer. The first signs of impending disaster usually appear on the leaves, initially as brownish or purple-black lesions at the margins, then spread over the rest of the blade. The stalk and stem turn to black slime. Sometimes, the infecting spores attack the tubers directly; when that occurs, damage appears first as dark blotches on the skin of the potato. As the incursion progresses, secondary invasions turn the weakened flesh to mush. Within a week, an entire field can be wiped out. This aggressive, funguslike affliction, Phytophthora infestans, has been ravaging more of the Russian crop than at any time in memory. When it turned up in the late 1990s, yields on some Russian plots were slashed as much as 70%. This summer, in some gardens, not a plant remained alive. Late blight ranks as world agriculture's most destructive disease. It's the same scourge that laid waste to Ireland in the 1840s, when more than a million people starved to death and at least as many were forced to leave their homeland. A century and a half of research has failed to subdue the highly adaptable organism. Moreover, in the past decade or so, P. infestans has acquired new traits that make it more threatening than ever; virulent, fungicide-resistant strains have turned up all over the world. In the few countries that can afford fungicides—mainly in North America and Western Europe—losses typically reach 15%, despite the application of chemicals in quantities unmatched for any other crop. In developing countries, where high cost and difficulties in distribution put fungicides out of reach, the annual toll already comes to billions of dollars. Says Wilbert Flier, a specialist at Plant Research International (PRI) in Wageningen, the Netherlands: “The impact of shifting Phytophthora populations, especially in the developing world, will cause dramatic constraints on potato production on a scale not experienced before.” In countries such as Russia, where for many people there's little to eat except potatoes, an epidemic could prove catastrophic, warns K. V. Raman, a professor of plant breeding at Cornell University and executive director of the Cornell-Eastern Europe- Mexico project (CEEM), an effort formed several years ago to keep the disease at bay. “The conditions prevalent in today's Russia,” he says, “are all too reminiscent of those of Ireland in the mid-19th century.” Even Western farm operations, for all their sophistication, could be overwhelmed by this persistent foe. One problem, says Harold Platt, a plant pathologist at the University of Prince Edward Island and the Agriculture and Agri-Food Canada Research Centre, is near-total dependence on fungicides, which are losing their effectiveness as resistant strains spread. “A hundred and fifty years of relying on a single management tool has been to our detriment,” he says. Another problem is that the United States and Canada, in particular, have come to rely on just a few vulnerable potato cultivars—most prominently, the versatile Russet Burbank, great for baking and the mother of most fast-food French fries, and good “chippers,” such as Ranger. “As potato diversity shrinks and Phytophthora strains multiply,” says Platt, “entire crops are at risk of being wiped out.” In response to the burgeoning risk, scientists in 1996 established the Global Initiative on Late Blight (GILB), an undertaking of some 700 researchers in 76 countries to conduct and coordinate research into the potato and the pathogen. The same year, in recognition of the special vulnerability of Russia and Eastern Europe, a group of plant pathologists at Cornell undertook to organize CEEM. Such efforts are beginning to pay off as researchers uncover potential vulnerabilities in the pathogen and outline better defensive strategies. ## Home in Toluca Much remains to be learned about late blight, but there is general agreement on its place of origin: the Toluca Valley, an hour and a half drive southwest of Mexico City. The valley is the center of P. infestans diversity. (Once classed as fungi, phytophthorae are in fact oomycetes, or water molds.) Although travelers carried the potato (Solanum tuberosum) from the Americas back to Europe as early as the 1500s, the disease seems not to have made the trip until the 1840s. Initially, when P. infestans did appear in Europe, it was unstoppable. It was only thanks to the discovery of the organism in the 1860s—and fungicides to fight it—that the Irish disaster wasn't more common. In countries that have been able to afford fungicides, frequent applications during the growing season—although imperfect, expensive, and hardly environment friendly—have held the disease at bay. But even that is changing. No fungicide has ever been found to which P. infestans could not ultimately adjust. Metalaxyl, for years the most commonly used, appeared increasingly impotent starting in the 1990s. And it was never effective against established infection. Cultivated potato varieties that in the past showed a measure of resistance to late blight, moreover, succumb readily to newer strains. Indeed, no potato has ever been developed with defenses that Phytophthora could not ultimately breach. And the attacker's arsenal is growing more elaborate. Until recently, most infections outside Mexico were caused by a single type of P. infestans (A-1), which reproduces asexually and can survive only in the potato's tissues. Infected tubers used for seed, left in cull piles, or unharvested in the ground have been the sources of spores from one growing season to the next. But starting in the late 1980s, a second mating type, or “sex” (A-2), previously limited to the Toluca Valley, escaped from Mexico, allowing sexual reproduction with A-1 in new areas. Individually, A-1 and A-2 produce sporangia, reproductive bodies that are short lived and require a moist environment. But when A-1 and A-2 are introduced to each other, they mate to form multitudes of thick-walled oospores that can persist independent of the host plant—in soil and during drought, for example. Sexual recombination also allows the organism to adapt more readily to adverse conditions. The consequences are already apparent. In the past, most Phytophthora races in North America had one, two, or at most three virulence genes; in Western Europe they had no more than four or five. In recent tests around St. Petersburg, 80% of the Phytophthora races had six or more such genes. Some had as many as 10. In addition, in the 1990s, especially aggressive and fungicide- resistant strains of the simple A-1 type started to appear. For most countries, fungicides have never been an option. And the new fungicide- resistant races of P. infestans have upset the balance of power even in rich countries. Everywhere, in short, it's assumed that the most promising and sustainable solutions will involve not new fungicides but genomics: genetic manipulation aimed at deactivating the organism or engineering potatoes that have “durable resistance,” lasting 10 years or more. Although the genomics projects are young, they are making progress. ## Gene warfare The organization coordinating the counterattack on P. infestans is the 6-year-old GILB, which held its triennial meeting in Hamburg, Germany, last summer. The session yielded some encouraging news. Phytopathologist Christiane Gebhardt of the Max Planck Institute for Plant Breeding Research in Cologne, for example, reported the first-ever cloning of a potato gene that confers resistance. The gene (R-1) engineers a sort of pyrrhic victory called hypersensitive response, in which cellular suicide at the site of invasion isolates the pathogen by destroying the plant tissue around it. Although Phytophthora long ago evolved ways around this gene and similar ones, the cloning of R-1 is an important step. It is located on a DNA “hot spot” containing genes that code for other known defenses against viruses, bacteria, mildew, and even nematodes. In addition, its genetic structure appears to resemble those other genes, an observation that might contribute to a clearer understanding of how these defenses work. A Dutch group led by E. Van der Vossen of PRI in turn reported the first-ever cloning of a gene that plays a role in another kind of defense, called rate-reducing resistance, which allows for fewer infections or diminished sporulation. The gene, Rpi-blb, is found in a highly P. infestans-resistant but inedible Mexican wild potato called Solanum bulbocastanum. And more genes are coming. Just weeks before the conference, a worldwide research consortium funded prominently by the multinational agribusiness Syngenta announced that it had accomplished a first-run “shotgun” sequence of Phytophthora's huge 237-megabase genome. According to Marc Law, Syngenta's Fungal Program leader, the consortium sequenced 75,000 expressed sequence tags (ESTs), telltale sequences that code for biologically significant proteins. Among those ESTs, says Law, were identifiers of both “pathogenicity factors” and “avirulence genes,” which elicit defense responses in the plant. As a bonus, the researchers also found genes that encode Phytophthora enzymes for “housekeeping,” signaling, and cell-cycle regulation. The goal of the genetic studies, says Ralph Dean, director of North Carolina State University's Fungal Genomics Laboratory in Raleigh, is to “identify all genes in the pathogen and the host that are functionally responsible for controlling … whether you have disease or whether you don't.” Researchers then hope to use that knowledge to breed, find, or engineer resistant varieties. ## Updating the potato The traditional strategy against late blight has been to seek potatoes, whether in the wild or in germ-plasm archives, that might prove resistant. But resistance is not enough. A potato that's worth its salt must be edible too, of course, and possess the literally scores of characteristics that make for commercial success. For example, says Kenneth Deahl, head of the late-blight project at the U.S. Department of Agriculture's (USDA's) Beltsville Agricultural Research Center, near Washington, D.C., “I have a potato right now that's resistant.” In size and shape, however, he says it's more like a peanut than a potato. Or take the cultivar Lenape: It's “resistant to late blight and a great ‘chipper,’” he says. “But it's also poisonous.” A more cutting-edge technique than combing through germ-plasm archives is learning how some potatoes recognize the pathogen and elicit a defensive response. Of the two main types of resistance, hypersensitive response is the more straightforward—a process thought to involve “gene-for-gene recognition,” in which a single resistance gene in the host recognizes a protein produced by a particular gene in the pathogen. The problem with single-gene resistance, says Deahl, is that Phytophthora is “an artful creature,” and it can get around that kind of resistance with a simple mutation. Considered more promising, therefore, is rate-reducing resistance, which is based on sets of genes that might collaboratively inhibit infection. And there's no dearth of resistant potatoes on which to draw. The largest group addressing the challenge through molecular genetics is the Potato Functional Genomics program, funded by the National Science Foundation. It includes Barbara Baker, a molecular biologist at the University of California, Berkeley; plant pathologist William Fry of Cornell; John Helgeson, a U.S. Agricultural Research Service plant pathologist at the University of Wisconsin, Madison; and The Institute for Genome Research in Rockville, Maryland. The project has so far generated 60,000 ESTs from core potato tissues: shoots, leaves, stolons, tubers, and roots. It might also be possible to learn something from “not-potatoes,” says Sophien Kamoun of Ohio State University, Wooster. He is looking at Arabidopsis, for example, because he says it “exhibits active defense responses [including hypersensitive cell death] to P. infestans.” And he wonders whether resistance genes from such nonhost plants can be transferred to the potato. At the University of Victoria in British Columbia, molecular biologists William Kay and Santosh Misra say they have already achieved something of the sort. They've engineered potatoes with genes encoding segments of antimicrobial proteins from silkworm moths and honey bee venom—and the plants have shown late-blight resistance. Some wild Mexican and South American potato species produce toxic glycoalkaloids that appear to help them resist insects. John Bamberg of the USDA Agricultural Marketing Service's Potato Project in Sturgeon Bay, Wisconsin, is studying how they work and whether these substances might confer resistance to late blight as well. A caveat, he acknowledges, is that the very toxins that make some potato varieties resistant to late blight might also make them poisonous to people and livestock. Some researchers are thinking about finding ways of designing plants to confine glycoalkaloids to the aboveground plant. One possibility might be to make them sunlight-activated, sparing the plant from disease without poisoning the tubers. And Dilip Shah, at the Donald Danforth Plant Science Center in St. Louis, is studying a vaccinelike procedure to see whether exposing the potato plant to the pathogen's proteins can stimulate generalized defenses. Understanding the products of resistance genes and their biochemical interactions with the pathogen could put scientists a step closer to conferring resistance to plants that lack it. As Helgeson puts it, “What we need to know is, what's the product of these genes? What do they do? Look at the dialogue.” Whatever the dialogue, it's not likely to be produced by old-fashioned crossbreeding of potatoes. This has never been an easy affair, because many of the wild potatoes in which resistance genes have been found are genetically diploid (having two sets of chromosomes), whereas tuberosum, the world's beloved, is an unwieldy tetraploid (with four sets). Helgeson sees hope in the news from Hamburg, however. Now that resistance genes have begun to be cloned, he says, it might be possible to put them “straight into a tetraploid.” He thinks that in the next 5 years, researchers will clone and sequence three, four, or even more such genes. From there, it would not be long before those genes could be “pyramided” into a single supercultivar. “Of course,” says Helgeson, “getting McDonald's to accept a ‘transgenic’ potato is another matter.” 9. REGULATORY RESEARCH # A Centennial Letdown for FDA's Biologics Group 1. Bruce Agnew* 1. Bruce Agnew is a writer in Bethesda, Maryland. A planned overhaul of CBER that would take away its special status as both a regulator and a researcher has staff members threatening to quit Do regulation and research mix? New leaders at the Food and Drug Administration (FDA) are pushing a big shakeup of the division that oversees biologics in a way that seems to de-emphasize research, although they cite other reasons for making changes. With little advance warning and no input at all from his scientific advisory panel, FDA Deputy Commissioner Lester Crawford declared on 6 September that much of the Center for Biologics Evaluation and Research (CBER)—which regulates therapies ranging from monoclonal antibodies to gene transfer—would be transferred to the Center for Drug Evaluation and Research (CDER), which regulates more conventional, chemically derived small-molecule drugs. Crawford said the consolidation—the precise details of which have not been worked out—will make the review of new drugs more efficient and consistent. Over the past few weeks, however, many CBER researchers and outside scientists have begun arguing that the real purpose of the move is to strip away CBER's special status as a regulator that also supports substantial intramural research. This self-directed program, which is based on the campus of the National Institutes of Health (NIH), is supposed to keep regulators at the cutting edge of fast-moving areas of biotechnology. The research effort is the envy of other FDA divisions that don't enjoy such free rein, and some FDA observers—including drug companies that help pay FDA's costs—have long argued that intramural research should be trimmed. The overhaul came as a complete surprise to most CBER staffers. They were planning to celebrate the division's 100th anniversary this fall and had already prepared a history, passed out commemorative coffee mugs, and scheduled a symposium for late September. Then the FDA bosses rained on their parade. CBER's friends on the outside were shocked. “There is no good rationale for what is being proposed,” says Leslie Benet, a professor of biopharmaceutical sciences at the University of California, San Francisco, who chaired an FDA advisory committee that strongly endorsed CBER's researcher-regulator model 4 years ago. Under decisions that Crawford has made so far, CBER will lose authority over a wide array of therapeutic biologics, including monoclonal antibodies, cytokines, growth factors, enzymes, interferons, proteins extracted from animals or microorganisms, and some immunotherapies. These products have moved into the medical mainstream, says FDA Principal Associate Commissioner Murray Lumpkin, who co-chairs a working group that is hammering out the details of the consolidation, and they “need to be under one management umbrella and need to be overseen from a clinical perspective”—although with due attention to the special manufacturing problems posed by biologics. CBER Director Kathryn Zoon strongly disagrees. “The science behind these [biologics] and the scientific issues with these products are not all solved,” she told the FDA Science Board—an advisory committee of non-FDA scientists—on 25 October. “And the need for having a research-reviewer model to deal with these issues continues to be important.” CBER will retain authority over the transferred biologics when they are used as reagents or as part of the manufacturing process, as well as its responsibility for such areas as blood and blood-related products, cellular therapy, vaccines, antitoxins, allergenics, xenotransplantation, and gene therapy (see table). “They're basically gutting CBER,” says Benet, even though it is meeting its performance goals, and “there's no evidence” that the move will improve efficiency or consistency. Benet also warns that the plan will retard biowar defense by driving away people with expertise that FDA needs to help develop and approve countermeasures. (Benet has just been named chair of a National Research Council-Institute of Medicine study committee on accelerating the research, development, and acquisition of medical countermeasures against biological warfare agents.) Whether CBER will, in fact, be “gutted” is an open question. Benet says the consolidation could sweep out 30% to 40% of CBER's roughly 900 employees and its$147 million budget. But staffing decisions haven't been made yet, says Lumpkin: “I'm not sure if that's in the ballpark or not.”

Researcher-reviewers who are transferred to CDER will be able to continue their current projects for at least a year, says CDER Director Janet Woodcock. She also indicates that there are no plans “at this time” to move them out of their labs on the NIH campus.

That doesn't strike CBER scientists as very reassuring. Amy Rosenberg, director of the Division of Therapeutic Proteins in CBER's Office of Therapeutics Research and Review (OTRR), told the FDAScience Board that many will simply quit. In a poll of OTRR laboratory personnel, about 90% said they would look for other jobs if the consolidation plan is carried out, she said. (Eighty-six of the 140 to 150 people involved replied to the poll.)

View this table:

However, Lumpkin's working group still has not determined precisely how many people and how much funding will be transferred to CDER, nor has it settled on a schedule for the transition. Lumpkin hopes to complete a transition plan in early January.

Why is FDA pushing such a controversial plan now? “That's a big Washington mystery, frankly,” says one Washington lobbyist. After all, Crawford had been on the job only about 7 months when he ordered the consolidation, and incoming FDA Commissioner Mark McClellan—who was sworn in 14 November—had not even been formally nominated. McClellan, who was then a member of President George W. Bush's Council of Economic Advisers, was kept informed, however.

Crawford declined to comment. But in a memo to FDA staff, Crawford said the issue had been under study since last fall, and that a consultant's report laying out possible options was given to him soon after he arrived in February. Then, during negotiations on extending the Prescription Drug User Fee Act—under which pharmaceutical companies will pay FDA an estimated \$1.2 billion over the next 5 years—Crawford said industry representatives complained about “consistency” of FDA decision making. (Whoever they were, these industry reps left no fingerprints. Neither the Pharmaceutical Research and Manufacturers of America nor the Biotechnology Industry Organization admits to pushing for the change.) Crawford finally concluded that transferring therapeutics to CDER would produce “less duplication of effort and greater consistency.”

FDA Science Board members were clearly miffed that Crawford didn't ask for their views. They didn't formally oppose the CBER-CDER consolidation at their 25 October meeting, but they made a point of not supporting it. “Before you move something, somebody's got to present a very logical and rational reason for doing that,” said Martin Rosenberg, retired senior vice president of GlaxoSmithKline. “I certainly haven't heard that.”

Science Board Chair Robert Langer, a professor of chemical and biomedical engineering at the Massachusetts Institute of Technology, reported to Crawford that the board “is concerned that the science not [be] disrupted and wants to understand better the reason for this move.” But Langer sees little chance that the consolidation plan will be blocked. After talking privately with FDA officials, “I think it is a done deal,” he says.

Lumpkin suggests that CBER scientists' initial dismay will pass. “It's not like CBER is going away, or CBER is somehow being minimized,” he says. “On the contrary, this incredible cutting-edge stuff—gene therapy, cellular therapy, stem cells—that's still in CBER, and it's going to get all the attention that CBER can give it.” Maybe Lumpkin is right; but right now, much of CBER's staff would prefer to be celebrating their 100th anniversary with an undiminished mandate.

10. PLANETARY SCIENCE

# Don't Ignore the Planet Next Door

1. Oliver Morton*
1. Oliver Morton is a science writer in London, U.K., and the author of Mapping Mars.

Is it time for a closer look at Venus? Some researchers say life could exist in its veil of clouds, and it could help us understand planets around distant stars

LONDON—Venus is the planet nearest to Earth, closest to Earth in size, and the brightest in Earth's skies. As such it would seem hard to overlook, yet overlooked it is. While NASA and the world's other space agencies lavish money on Mars—dispatching probes at an average of more than one per year—and eye other planetary prospects farther afield, such as Jupiter's moon Europa, they hardly spare a thought for Venus. The reason is water. Although Mars might look like a parched and frozen desert, its surface was marked by water in the distant past, and water may persist at some depth today. Water, the logic goes, means the possibility of life, in the past if not the present. Water thus makes a planet interesting. And water is something that Venus—with an average surface temperature of 460°C—conspicuously lacks.

Although inhospitable, Venus is not completely ignored. The European Space Agency (ESA) this month approved Venus Express—a mission to study the planet's atmosphere—for launch in 2005. But it's a cut-price project, cobbled together using instruments from ESA's Mars Express and Rosetta missions and built around a copy of the Mars Express spacecraft; it is not custom built for studying Venus. And even this modest effort was nearly cancelled earlier in the year because of budget problems.

Although Japan plans to launch a small satellite to study the atmosphere in 2007 or later, there is no major commitment to ongoing studies of Venus in any of the world's space agencies. NASA will have launched its first mission to look for Earth-sized planets around other stars well before it next sends a spacecraft to the Earth-sized planet next door. As Kevin Baines, a planetary scientist at NASA's Jet Propulsion Laboratory (JPL) in Pasadena, California, puts it, “There is little hope of finding life or signs of ancient life. So, Venus always seems to fall to the bottom of the list.”

But not all of his colleagues accept Baines's premise. A few planetary scientists are starting to think it might be wrong to assume that Venus is a hopeless prospect for finding life. Their optimism stems not from any new information about Venus but from looking at what is known in a different way. Although it clearly lacks any extensive bodies of liquid water, Venus might still be conducive to life, they argue. Indeed, according to David Grinspoon, a planetary scientist at the Southwest Research Institute in Boulder, Colorado, Venus is as good a place to look for life today as either Europa or Mars—maybe better. “The case for possible life there is really as strong as on any other planet,” says Grinspoon.

So far, Grinspoon and his fellow Venus devotees haven't won over many of their colleagues. One eminent astrobiologist muses that it's interesting that a science which until very recently was viewed as on the fringe should now have a fringe of its own. But researchers in that fringe have started publishing papers and presenting ideas at conferences about both life on Venus and ways to study it. And if they haven't convinced many that Venus might harbor life, they have another argument that seems more compelling: We should be taking a closer look at Venus in order to prepare for what we might find when we look for life around other stars.

Grinspoon first started thinking about life on Venus in the mid-1990s. While writing the conclusion to a book about Venus, he tried to put together a case for life on the planet, just to see if such a case could be made. “My devil's advocate case was good enough to convince me, not that there is life there, but that there could be,” he says.

The argument begins by noting that Venus might well have been as good a habitat for life as Earth or Mars were when the solar system was young; most opinion has it much cooler then than it is today, with every chance of liquid water. If Venus did not offer the right conditions for the origin of life—whatever they may be—it would still have provided a welcoming and clement landfall for any microbes on meteorites knocked off Earth or Mars. The chances of life on an early Venus are thus not that different from the chances of life on Mars at roughly the same time.

Unfortunately, both planets then underwent quite vicious changes of climate. On Mars, what surface water there might have been froze. Life would have been forced underground, where the planet's warmth would allow liquid water to cling on in deep aquifers and hydrothermal systems. It might persist there to this day. On Venus the problem was not the cold but the heat: a runaway greenhouse effect that boiled away the surface water. Grinspoon reasons that life on Venus, faced with the opposite problem of life on Mars, might have hit upon the opposite solution: migrating up into the sky to keep cool rather than down into the ground to keep warm.

Compared to its surface, the skies of Venus look positively alluring. The atmosphere contains some water vapor—although only a very little—and its clouds are at a sufficient height for that water to condense out in liquid form. Some of the cloud droplets at these altitudes are larger than the droplets in clouds above Earth are and thus are more than large enough to contain microbes. The clouds are continuous and permanent, and the individual cloud droplets stay aloft for months, so they could provide a reasonably stable environment. Thanks to presumed continuing volcanism, the clouds exist in an atmosphere rich in chemicals that living organisms might use to fuel their metabolisms, and there is plenty of sunlight for photosynthesis. Admittedly, the cloud droplets are composed of very highly concentrated sulfuric acid, and this might appear to be a showstopper. But microbes can survive in some very unlikely surroundings.

Indeed, since Grinspoon first started to advocate it, his devilish case for life above the hellish surface of Venus has received circumstantial support from studies of life on Earth. Earthly bacteria have been discovered in ever more acidic environments; some have now been found that thrive at pH levels as low as 0. And although it had long been thought that the only bacteria in cloud droplets were inert spores or were in suspended animation, recent measurements made in the Alps have shown that the bacteria in clouds can be metabolically active. If some earthly microbes can live in clouds and others in strong sulfuric acid, why shouldn't microbes on Venus have learned to do both at once?

In some ways, says microbiologist Dirk Schulze-Makuch of the University of Texas, El Paso, the permanent cloud cover of Venus might actually make a better home for microbes than the short-lived clouds of Earth. One possible energy source that venusian microbes might use, he speculates, is ultraviolet light. For decades, it has been known that there is something in the clouds over Venus that absorbs UV light very well. As yet, no one knows what it is—an organic pigment, perhaps?

Charles Cockell, a microbiologist at the British Antarctic Survey in Cambridge who wrote a paper about the astrobiological potential of Venus in 1999, is one of many who hold out little hope for such ideas of life in the clouds. Sulfuric acid is a powerful desiccating agent, and acid as strong as that in Venus's cloud droplets, he says, would pull the water straight out of any cells immersed in it. David Crisp of JPL, who chaired a panel that provided ideas about Venus to the recent decadal survey of planetary science done by the U.S. National Research Council, agrees. “[Schulze-Makuch and his co-author] make the assumption that there are water droplets, but that's fundamentally incorrect, as far as we know. There's no evidence for liquid water on Venus that's not bound in very, very concentrated solutions of sulfuric acid: 75% to 85% pure sulfuric acid.”

Grinspoon does not accept that there is no overlap between the range of pH values earthly microbes can tolerate and the range found in the clouds of Venus. But even if the clouds of Venus are too acidic for any Earth-like life, that does not rule out life of other sorts. Steven Benner, a biochemist at the University of Florida, Gainesville, points out that the idea that water is necessary for life is far from proven. Some chemical reactions that might be the basis of different forms of life take place best under conditions where water is excluded, such as those of superacidity. And Benner thinks that if we can't imagine life existing in the clouds, that might just show our lack of imagination.

However plausible the case for life in the clouds of Venus is, it will be difficult to test. Bringing a sample of Venus's clouds back to Earth sounds quite simple: Design a probe to dip into the atmosphere as it flies by the planet, scoop up a bit of its surroundings, and carry on along a trajectory that brings it back to Earth. A mixture of aerobraking techniques like those used by Mars probes and sampling canisters like those on the Stardust mission to sample cometary dust would do the trick.

But Grinspoon worries that gathering up a sample at such speed might smash the very things that are being sought. And Crisp points out that designing a sample-return canister that can bring powerful and poorly characterized acids back to Earth in a pristine form is no easy task. Even if you could bring a sample back, looking for life in it would require a secure containment facility here on Earth. If the laboratory slated for dealing with the samples to be returned from Mars were used, then that cost could be avoided, but that laboratory is more than 10 years off.

Attempts to sample the atmosphere are hampered by the lack of a thorough understanding of how the planet works. Although more than 20 spacecraft from the United States and the Soviet Union visited Venus in the 1960s, 1970s, and 1980s, big questions—such as how its atmosphere works, what its surface is like, and how the two interact—still have not been answered. Crisp argues that this lack of understanding has led to the belief that small missions to Venus, such as those in NASA's Discovery Program, will not be up to the task of solving the outstanding problems, while at the same time making ambitious missions very hard to plan, because questions still remain about the environmental conditions they would have to work in. Before the tantalizing question of life above Venus can be answered, more basic spadework needs to be done, but neither NASA nor other space agencies are showing the necessary commitment.

That commitment could be crucial not just to understanding Venus but also Earth-sized planets around other stars. When scientists start detecting—and a decade or so later actually studying—such planets, they won't be little ones like Mars or moons like Europa. Researchers will be seeing planets the size of Earth and Venus. “What happens if we go out and we find primarily Venuses?” asks Crisp. Venus is both very much like Earth, in size and orbit and composition, and profoundly different. Without understanding these differences—including what they mean for the evolution of life on such planets—multibillion-dollar astrobiological efforts to make sense of Earth-like planets around other stars could be very frustrating.

11. PROFILE: MICHEL BRUNET

# One Scientist's Quest for the Origin of Our Species

1. Ann Gibbons

Years of effort in hostile territory finally pay off for French paleontologist Michel Brunet, who discovered a fossil that might be the first member of the human family

POITIERS, FRANCE—The night after Michel Brunet found the jawbone of a human ancestor in the sandblasted desert of northern Chad, he got up twice just to look at it. While his team slept, Brunet shined his flashlight on the precious 3.5-million-year-old jawbone. “I had to make sure it was not a dream,” he recalls. “I had been looking for this for so long that I could not believe it was true.”

By that January night in 1995, Brunet, a professor at the University of Poitiers in France, had already made his name as a paleontologist's paleontologist, widely respected for his skill in finding fossils in some of the world's most remote and hostile sites. He had been strafed by a fighter jet in Afghanistan, arrested in Iraq, and lost a close colleague to malaria in Cameroon. Yet every year, he returned to the field, leading teams that collected thousands of specimens of all kinds of mammals—extinct monkeys, giraffes, rhinoceroses, hippopotamuses, and pigs. But one type of mammal had eluded him: a hominid, or member of the family that includes humans and their earliest ancestors. Until that January day, Brunet had never held an actual fossil, as opposed to a cast, of an early hominid. So when he cradled the jawbone in his hands, “for me, it was incredible.”

As it turned out, that jaw was just a forerunner. In July 2001, a member of Brunet's close-knit team of young French and Chadian researchers dug up a nearly complete cranium in Chad that has been called the find of the century. Many consider this 6-million- to 7-million-year-old skull the earliest known member of the human family. Although a few anthropologists question whether it is a hominid, no one disputes its importance: It is the only known fossil of a primate that lived in Africa when apes and humans had just diverged on their separate evolutionary tracks. When Brunet called his longtime friend and field colleague, paleoanthropologist David Pilbeam of Harvard University, to tell him of the find, Pilbeam predicted: “This will change your life.”

In a field peopled by celebrity scientists, it seemed to many that Brunet came out of nowhere. The find of the century was made by a man trained not in hominids but in paleontology—someone with 160 papers in French, German, and English journals on topics such as the predation of dung beetles by termites, an extinct monkey in Afghanistan, and dinosaur footprints in Cameroon. But as Brunet plugged away in fossil beds in Africa, Europe, and Asia, he trained himself to recognize clues from fossils and geology that point the way to hominid terrain. While high-powered teams of anthropologists searched for early hominids in the proven fossil beds of eastern and southern Africa, Brunet scoured the shifting sands of West African deserts, sometimes on a shoestring budget. “He is a very professional scientist who is the industrial standard for being single-minded,” says paleoanthropologist Bernard Wood of George Washington University in Washington, D.C.

Now, over a year after the discovery and a few months after the skull dubbed Toumaï was introduced as “The Earliest Known Hominid” on the cover of Nature (11 July, article p. 145),” Brunet's life has indeed changed. He has become a paleostar, rocketed to the highest strata of international science. At 62, after a life of being little known outside his field, he is suddenly in demand everywhere. As Science shadowed him for several days last month, he was feted and presented with a medal of honor by the president of his region in France; courted by an American documentary producer; asked to autograph a menu by a well-known chef; and bombarded by e-mail requests seeking viewings of the new fossil and his presence at conferences.

All this bemuses Brunet, who in Poitiers, with his neat gray beard, wire-rimmed spectacles, and sweater vests, looks more like a slightly rumpled European academic than an intrepid fossil hunter out of National Geographic. “I am French, poor, crazy, a Socialist,” he volunteers. But make no mistake: Brunet can be formidable, particularly when his ire is raised in defense of his work or team. “He is very determined,” says paleoanthropologist Yves Coppens of the Collège de France in Paris.

## The making of a fossil finder

He is also a local boy who made good. During World War II, Brunet lived with his grandmother in a village near Poitiers, 350 kilometers southwest of Paris. He didn't start school until he returned to his parents in Versailles at age 8. So he spent his early years outdoors, developing a love of nature. “I am happiest when I sleep under a blanket looking at the stars,” he says.

After college and a Ph.D. at the University of Paris, Brunet joined the faculty of the University of Poitiers and became a specialist in hoofed mammals, tracking their migrations into Europe almost 40 million years ago. It was a respectable, satisfying career for someone who never met a mammal fossil he didn't like, as graduate student Fabrice Limoreau says of Brunet. But then in 1976, Brunet heard of Pilbeam's search for fossil apes in Pakistan. At the time, researchers thought an 8-million- to 13-million-year-old ape, then called Ramapithecus, might be an ancestor of hominids.

Brunet, who had studied human paleontology in graduate school, made a momentous decision with his colleague Emile Heintz, a paleontologist at the National Center of Scientific Research (CNRS) in Paris: to seek extinct apes across the border from Pakistan in Afghanistan. “I am a Homo sapiens, and I want to try to answer: From where did we come?” he says.

Switching to apes meant moving tens of millions of years up the geologic time scale, to the period from 8 million to 5 million years ago, when the earliest human ancestors lived. But although Brunet zeroed in on a promising time and place, searching for fossils is not like collecting shells by the seashore, as he is fond of saying. For every rare hominid fossil, paleontologists usually find thousands of fossils of other animals. In Afghanistan, Brunet's team found many mammals, including rodents and a monkey, but no apes. And the work was dangerous. In 1978, his team was standing on a flat rooftop in Kabul, watching Soviet-made fighter jets strafe the city. One roared low overhead three times and then fired at them; luckily, the pilot missed. Brunet had also begun fieldwork in Iraq, where one day, while seeking a hotel room in a small town, he was arrested—though he never found out why—and then released.

## Westward bound

By 1980, both Afghanistan and Iraq were too dangerous to work in, and Pilbeam had recognized that Ramapithecus was no hominid but a likely orangutan ancestor. Yet Brunet was still set on finding hominids. So he and Pilbeam, who by then were working together to analyze the animals that lived alongside Ramapithecus in Pakistan, studied the map of Africa.

Starting with Louis Leakey's discovery of a hominid in 1959, all of the oldest hominids had been found in east Africa, at sites of ancient savannas along the Great Rift Valley, with another set of slightly younger fossils turning up in southern Africa. But before 1 million years ago, there were no known hominids from western Africa. This distribution had prompted Coppens to propose that while hominids arose in the savannas of east Africa, other apes, such as the ancestors of chimpanzees and gorillas, clung to the dense forests on the west side of Africa. It was an idea that Brunet longed to test. “The idea was to prove Coppens's hypothesis right or wrong,” he says. He and Coppens, 68, had been friends as well as rivals since the 1960s.

Coppens had found many mammal fossils, including a partial skull of a relatively recent (less than 1 million years old) Homo in Chad in 1961, and had scouted older sites in the bed of ancient Lake Chad. Brunet thought the fossils suggested that the shores of the ancient lake were a magnet for many mammals, perhaps including hominids. “There was no scientific reason why hominids should not be there,” says Brunet.

Brunet and Pilbeam set their sights on two nations with close ties to France—Chad and Cameroon—2500 kilometers directly west of the fossil beds of east Africa. Brunet “plugged away and got little bits and pieces of money from everywhere, including a grant from the government of Poitou-Charentes region to study the effect of goat grazing,” recalls Pilbeam. The field permits came through first in 1984 in Cameroon, where the French foreign service had close ties. Brunet sums it up: “Two young guys—one French, one American—decided to go west. Everyone thought we were crazy.”

The nine field seasons spent in the jungles of Cameroon, however, were discouraging. They found Miocene sediments but only one lone mammal fossil and no hominids. No hominids meant no more funds, and Pilbeam dropped out. Brunet persisted but paid a terrible price: His close friend, geologist Abel Brillanceau, died of drug-resistant malaria in 1989. For Brunet, the loss was devastating.

But he kept scouting new sites, including some in the desert of Chad, which he toured in a rented car with barely enough water to brush his teeth. Finally, in November 1993, the government of Chad invited him to work in the Djurab Desert, which had been closed to researchers since 1965. By January 1994, Brunet was in the field, “sweeping and sifting” the dunes in what was once ancient Lake Chad, which has expanded and contracted many times over millions of years. He formed a scientific alliance, called the French-Chadian Paleoanthropological Mission (MPFT), with the University of N'Djamena and the Centre Nationale d'Appui à la Recherche, but the logistics were daunting. Says Brunet: “The desert is a wonderful place that can turn very quickly to hell.”

Over the past 9 years, the MPFT researchers have dug tents out of sand as if it were snow; worn ski masks as they scoured the sun-bleached lakebed for fossils; and unloaded pallet after pallet of bottled water, trucked in with help from the French army. The fossil beds are in disputed terrain, where warlords have battled during 2 decades of war, and Brunet has been threatened at gunpoint. Metal objects buried in the sand are avoided because they might be mines. “This may be the most difficult to work of any of the hominid sites,” says paleoanthropologist Tim White of the University of California, Berkeley.

But the windstorms that can trap researchers in their tents for days are also their allies, eroding 3 centimeters of sandstone a year, sending dunes sailing across the flat desert like waves on a sea, and exposing fossils that have been buried for millions of years. To date, MPFT has found 8000 fossils from more than 300 sites in one part of Chad. That bounty gave Brunet the confidence to predict that he would find hominids, because the gallery forest rimming the ancient lake was clearly the stomping ground for many mammals. Even so, Brunet says it took him years to learn how to find a hominid in Chad, detecting how fossils of a certain size and type present themselves at a particular site, in a particular light. “Sometimes when you are in the field, you see something, you get a feeling,” says Brunet.

He got such a feeling that January morning in 1995, when he spotted the 3.5-million-year-old jawbone. Informally, he calls it Abel, for his lost friend; scientifically, he classified it as a new species of australopithecine, Australopithecus bahrelghazali. That jaw was the first fossil to show that geographically, there is “a third window” of early hominid evolution—in West Africa, notes Pilbeam. But some researchers question Brunet's naming of a new species, because the jaw “falls within the range of variation” for Lucy's species, A. afarensis, says William Kimbel of the Institute of Human Origins at Arizona State University in Tempe. For now, there is no consensus on the jaw's classification.

## The first hominid?

Once Brunet started finding mammals that were more than 6 million years old, he predicted, only half jokingly, that he would find a hominid of that age. “You are working in sediments younger than 6 million years,” he said in a playful challenge to White, who has found a rival, younger contender for the earliest hominid. “You are going to lose.” Brunet's graduate student, Jean-Renaud Boisserie, recalls: “After the discovery of Abel, he was sure he would discover something exceptional and more ancient than the hominids in east Africa. He was so sure that I was convinced also.”

They had to wait 6 years. Then on 19 July 2001, after Brunet had left the field for the season, he got a call from his team: A young Chadian student, Ahounta Djimdoumalbaye of the University of N'Djamena, had unearthed a nearly complete cranium.

When Brunet saw that the fossil's face and teeth resembled those of a hominid, rather than a gorilla or chimpanzee, he knew he had the find of a lifetime (Science, 12 July, p. 171). The beds containing the skull had already yielded 42 species of animals, from fish and rodents to wild boar, which were used to date the fossil to between 6 million and 7 million years old, as the desert surface has no volcanic ash for radiometric dating. Brunet is now seeking an oil company to drill a core to collect and date the underlying ash.

No less than the president of Chad nicknamed the skull Toumaï, which means “Hope of Life” in the Goran language, and Brunet classified it in a new genus and species, Sahelanthropus tchadensis. Even his rivals were impressed. “I take my hat off to him for achieving what he did in Chad,” says Collège de France paleontologist Martin Pickford, who also has found a rival early hominid in east Africa. “It's not an easy place to work.”

Nor will it be easy to prove beyond a doubt that Toumaï is a hominid. The partial skull is so ancient that it shows a mixture of primitive features found in apes that came before it and more modern features found in hominids that came later. For example, the brain is small and chimp-sized. But the lower face is flat, like that of later hominids and unlike the protruding snout of chimps and gorillas. Brunet also notes that the upper canines are small and show a wear pattern on top of the first lower premolar like that of hominids, rather than deep sharpening along the edges, seen in gorillas and chimps.

But not everyone is convinced, partly because different researchers battle over what traits are most important in defining a hominid. “If you define hominids by a reduction in the canines and premolars, then it's a hominid,” says paleoanthropologist Carol Ward of the University of Missouri, Columbia. “But if a hominid is going to be defined by walking upright on two feet, you can't tell [if Toumaï is a hominid].”

Indeed, in a letter to Nature last month, Pickford and three other researchers argued that upright walking, not canine-premolar shape and size, is the hallmark of a hominid. Pickford and colleague Brigitte Senut of the National Museum of Natural History in Paris repeated their assertions that their find, 6-million-year-old Orrorin tugenensis, has signs of upright walking and so is a “more likely” candidate for earliest hominid. In contrast, wrote lead author Milford Wolpoff of the University of Michigan, Ann Arbor, “we believe that Sahelanthropus was an ape.” The letter's headline suggested that the fossil's genus name, which means Sahel man, should be changed to Sahelpithecus, for Sahel ape. And in interviews with the press, Pickford and Senut went even further: They called it a gorilla ancestor.

Such criticism infuriates Brunet. “It is crazy,” he scoffs, gesturing irritatedly with a cast of Toumaï in his hand. Although he welcomes scientific debate, he says that the researchers appear to be promoting their fossil at the expense of Toumaï. In his response in Nature, he accuses the scientists of “misrepresenting” Toumaï's morphology. He notes that Senut and Pickford have viewed Toumaï only briefly and that Wolpoff has never seen it. “Toumaï is absolutely not a protogorilla!” he says.

On that point, he has a lot of company. “The dental characters that suggest it is a hominid are exactly the characters that make it not a gorilla or other ape ancestor,” says White. Agrees Wood: “I don't think there's any chance it is a gorilla.”

As Brunet analyzes Toumaï, he has “the good sense,” says Wood, to seek the advice of specialists to help mine the hominid skull for its data. “You can't be an expert on everything, so he's playing the field to see who the good people are.”

Meanwhile, Brunet is eager to return to the field to find skeletal remains that could illuminate how Toumaï walked. Characteristically, he predicts that even older sites he has found hold the promise of even older primates, such as the common ancestor of chimps and humans.

But Brunet, whose heart is pumping with the help of four stents, is also aware that he is in a race against time. And he is intensely conscious of the price he paid to find a hominid, mentioning the loss of his friend. “People say I am lucky. I am not lucky,” he claims, throwing up his hands. “I have given too much.”

But a few hours later, he is patiently discussing Toumaï with a child at 11 p.m. after a packed public lecture in a small town near Poitiers, clearly enjoying what Pilbeam calls “the hominid aura.” To friends who have followed his career closely, it is fitting that this veteran fossil hunter, schooled in the anatomy of mammals and determined to leave no fossil stone or bone unturned, is the one who discovered Toumaï. “It's a beautiful trajectory,” says paleontologist Jean-Jacques Jaeger of the University of Montpellier II, “the life history of a mammal paleontologist.”