# News this Week

Science  18 Jan 2002:
Vol. 295, Issue 5554, pp. 418
1. FORENSIC SCIENCE

# Fingerprinting Doesn't Hold Up as a Science in Court

1. Adrian Cho is a freelance writer in Boone, North Carolina.

When the U.S. Supreme Court set new standards 9 years ago designed to keep “junk science” out of the courtroom, few would have guessed that evidence based on one of the oldest and most widely used forensic techniques in the world might be in jeopardy. But earlier this month, a federal judge ruled that old-fashioned fingerprinting doesn't meet the Supreme Court's standards. The ruling won't knock fingerprint examiners out of the courtroom, but it may limit the claims they can make. And it opens the way for challenges to the scientific credibility of ballistics and other forensic techniques.

In 1993 the U.S. Supreme Court clarified the Federal Rules of Evidence specifying what counts in court as science. In Daubert v. Merrell Dow Pharmaceuticals, the court said that a technique or methodology qualifies as science only if it can be tested, is subject to peer review, possesses known rates of error, and is generally accepted as science. In the past 3 years, defense lawyers and skeptics have argued repeatedly that fingerprint identification—the practice of matching a “latent print” found at a crime scene to a copy taken by authorities—does not satisfy the court's standards. More than 20 state and federal judges had rejected such arguments, but on 7 January, Judge Louis H. Pollak of the U.S. District Court for the Eastern District of Pennsylvania found that fingerprinting fails three of the four Daubert standards.

Pollak, a former dean at the University of Pennsylvania and Yale law schools, ruled on whether fingerprint evidence could be introduced in a trial in his court. He rejected the argument that the technique had been tested both by nearly 100 years of courtroom experience and by examiners checking each other's findings. Fingerprint identification also has not been subject to peer review, he found, in part because fingerprint examiners do not constitute a “scientific community.” The judge further found that the rate at which practitioners make errors has not been quantified.

Much of the controversy surrounding fingerprinting stems from the subjectivity involved in comparing prints. Examiners systematically note the overall pattern of the ridges; places where individual ridges stop or split, which are known as Galton points; and details on the individual ridges, such as the positions of pores. But ultimately the examiner relies on his or her ability to recognize patterns to decide whether two prints match, says Pat Wertheim, a forensic scientist with the Arizona Department of Public Safety in Tucson.

But although their judgments are subjective, fingerprint examiners claim their method allows them to make matches with absolute accuracy. They attribute any error to mistakes made by the examiner and argue that such “practitioner error” does not fall under the scrutiny of Daubert. Pollak ruled, however, that practitioner error must also be quantified, which critics and supporters agree has never been done.

Even though he found that fingerprinting fails the Daubert test, Pollak didn't bar fingerprint evidence entirely from the trial. He ruled that fingerprint examiners for both sides could point to characteristics of the fingerprints presented as evidence, but he forbade them from declaring whether two prints match.

The ruling applies only to one case, but it will likely set a precedent by which other judges will find fingerprinting unscientific, says David Faigman, a law professor at Hastings College of the Law in San Francisco. He adds that Pollak's ruling should spur the necessary testing, which will likely prove fingerprinting reliable: “The FBI and others will begin to do the research that Daubert has called for all along.”

However, David Ashbaugh, a forensic scientist with Ridgeology Consulting Services in Hope, British Columbia, and a staff sergeant in the Royal Canadian Mounted Police, says that Pollak misunderstood the arguments made in support of fingerprinting. “This is just one judge,” Ashbaugh says. “There will be opportunities to present our case to other judges.”

In the meantime, James Starrs, a law professor and forensic scientist at George Washington University in Washington, D.C., says that fingerprint examiners have a better chance of satisfying the flexible Daubert standards by declaring fingerprint identification a form of technical expertise, similar to accident reconstruction, rather than science. But fingerprint examiners aren't willing to strike such a bargain, Wertheim says. “That's the chicken's way out,” he says. “We all feel that fingerprint identification is good science.”

Both critics and supporters of fingerprinting expect lawyers to use Pollak's decision to try to appeal convictions and to question the validity of other types of forensic science. Suspicion will likely fall first on ballistics: the process in which a bullet is matched to a smoking gun.

2. ANTIQUITIES

# Global Support Grows for Afghan Restoration

1. Andrew Lawler

As Afghanistan settles into a precarious peace after the ousting of the Taliban regime, scholars are taking stock of the most recent destruction of Afghanistan's rich cultural heritage. Initial reports are grim: Ancient murals were trucked away from the niches around the dynamited Buddhas of Bamiyan, every human statue in the national museum in Kabul was destroyed, and the museum itself may be beyond repair, say UNESCO officials. But there is growing international support for restoring and possibly even rebuilding important cultural artifacts.

The most dramatic example is a plan by a Swiss architect to rebuild the 53-meter-high standing Buddha at Bamiyan, whose 1700-year reign as the world's largest Buddha ended last March when the Taliban regime destroyed it and another similar but older sculpture (Science, 9 March 2001, p. 1873). Paul Bucherer- Dietschi hopes to use digital data from photographs to create a 1:10 scale model of the Buddha at a museum he founded in Bubendorf, Switzerland, as a temporary home for Afghan artifacts. The model, likely to cost about $1 million, would be the first step in recreating the original in the Afghan cliffs. Bucherer-Dietschi, who last week returned from a 6-week tour of Afghanistan under a UNESCO contract, says that Raheen Makhdoom, Afghanistan's new minister of information and culture, told him he supports the reconstruction. A former professor of art history, Makhdoom announced recently that the government wants to sponsor an international conference in May to assess what can be done to repair the damaged site, including rebuilding the statue. The reconstruction would be more than a symbolic emergence from the Taliban's policies of cultural destruction. It would also be a huge boon to Afghanistan's once-thriving tourism industry. But the ambitious project poses formidable engineering as well as fund-raising challenges. “The cliffs were heavily damaged from the explosions, so stabilization is a priority,” says Bucherer- Dietschi. Although some debris remained at the base of the two Buddhas when he visited the site, he says that local residents told him that much of the rubble had been hauled away in trucks to be sold. Some 150 square meters of murals in the nearby niches also vanished, he notes. The details of how to rebuild the Buddha and restore other artifacts must be left to international experts, he adds. While Bucherer- Dietschi focuses on the destroyed Buddha, UNESCO officials are trying to assess the damage and restore order to the cultural relics that remain. Tracing the rubble and murals “is hopeless—we don't have the money or personnel,” says Christian Manhart, who heads UNESCO's Asian cultural heritage division. “Our priority is to conserve what's still there.” UNESCO already has distributed about$1000—"a huge sum in Kabul,” Manhart says—to three Afghan archaeologists to purchase materials and put the rubble from the museum into boxes for later identification.

Sadly, little appears salvageable. Manhart says the museum's collections—undermined by 20 years of war and chaos—were “systematically destroyed” by the Taliban, whose strict reading of Islamic law made them hostile to all representational images. “It's worse than we thought,” says Manhart, noting that other artifacts were likely looted. The one exception is prehistoric shards boxed in the museum basement. “They didn't touch those,” adds Manhart. “There was no real market value to them.” The museum itself may have to be replaced, he says.

UNESCO is assembling a team of scholars, primarily Afghan researchers in Europe and the United States, to conduct a detailed assessment of ancient sites. James Williams, a UNESCO cultural heritage officer, says that there are early reports of extensive damage to the Zoroastrian complex of Surkh Kotal near the Pakistan border, to a variety of mausoleums in Herat, and to the 9th century mosque of Haji Piyada in Balkh. The unique site of Hadda near Jalalabad, which combines Hellenistic and Buddhist styles, is rumored to have been destroyed, he adds. And thousands of excavated artifacts remain unaccounted for, including a spectacular Soviet find in the late 1970s of Hellenistic-influenced gold objects at Tilya Teppe in north-central Afghanistan.

There are no plans at present to resume archaeological digs, says Roland Besenval, an archaeologist at the Guimet Museum in Paris who learned during a visit last month to Kabul that officials first want to assess the damage and clear land mines. The Italian and German governments have pledged support for rehabilitating the museum, and France, Austria, and Japan may also chip in money for cultural heritage assistance. In addition, Italy has provided $160,000 for conservation and archaeological training of Afghan workers involved in the repairs, and Japan has set aside$76,000 to track looted Afghan objects. Unfortunately, money can't mask the fact that a good deal of Afghanistan's heritage either has been wiped out or now rests in the hands of foreign collectors.

3. MATERIALS SCIENCE

# Mammalian Cells Spin a Spidery New Yarn

1. Robert F. Service

Not even the priciest threads from New York's fashion district can match the wonders of a simple spider web. Spider dragline silk is stronger than Kevlar and stretches better than nylon, a combination of properties seen in no other fiber. That's had entrepreneurs and scientists scheming for more than 100 years to find a way either to farm spiders or, lately, to transfer their silkmaking genes into organisms that can produce enough silk to be useful. None have succeeded—until now. On page 472, a team led by researchers at Nexia Biotechnologies near Montreal, Canada, reports splicing dragline silk genes into mammalian cells and showing for the first time that harvested recombinant proteins can be spun into strong, lightweight fibers.

The new progress “is highly encouraging,” says Randy Lewis, a molecular biologist and spider silk expert at the University of Wyoming in Laramie. “It opens up a lot of things on a practical level and on a research level.” On the practical side, Lewis says that if the process of harvesting silk from cell cultures is perfected, it will lead to ultrastrong, flexible fibers for everything from artificial tendons and ligaments to lightweight body armor and high-strength composites. And on the research side, teams can now explore how changes in the silk genes and proteins affect the strength and flexibility of the fibers.

This promise is injecting new hope into a field in which progress has been “agonizingly slow,” says team member Steve Arcidiacono, a fiber-spinning expert with the U.S. Army Soldier Biological Chemical Command (SBCCOM) in Natick, Massachusetts. SBCCOM and other teams have worked for more than 10 years to splice spider silk genes into other organisms in hopes of recovering enough silk to produce bolts of high-strength material. And although they've inserted the genes into bacteria, yeast, and plants, the result has always been disappointing: insoluble silk proteins that clump together inside the cells. Even when the proteins have been extracted and purified, researchers have managed to turn them only into worthless, brittle fibers at best.

The Nexia researchers thought they might get better results by transferring silk genes into certain mammalian cells that more closely mimic those used by the spider itself. In spiders, specialized epithelial cells produce and secrete a pair of proteins in a water-based solution in a spider's silk gland. As these proteins are pushed out of the gland, they self- assemble into fibers, although the details of this process remain unclear.

The Nexia team, led by molecular biologists Anthoula Lazaris and Costas Karatzas, spliced the silk genes into two different cell lines: bovine mammary cells, epithelial cells that excel at secreting proteins outside the cell; and hamster kidney cells, which are adept at producing large volumes of recombinant proteins. Both cell lines worked, each secreting soluble silk proteins outside the cells, where they could easily be collected.

The Nexia researchers then teamed up with Arcidiacono's group to spin the proteins into fibers. For this first study they spun fibers from just one of the proteins, dubbed MaSpI. The army researchers first concentrated the MaSpI proteins in water, then extruded them through a tiny hole at the end of a syringe and into another solution containing methanol, a change of environment that prompted the proteins to assemble into continuous fibers. And impressive fibers they were: threads that are lighter yet tougher than Kevlar and nearly as elastic as nylon.

That's still not quite as good as native dragline silk, which has even more flex. That difference may be because the fibers are made from only one of the two proteins spiders use to spin their fibers. Karatzas says his team will soon try to spin fibers from both proteins to see if this improves the fibers' properties.

Making bigger proteins may also help. Native silk proteins are heavyweights, each weighing some 150 kilodaltons, whereas those produced by the recombinant method are about 60 kilodaltons. Karatzas says his team has already produced heavier proteins by splicing three copies of the gene next to one another. The Nexia researchers plan to test these to see whether they make better fibers as well.

If either scheme works, it may help propel recombinant spider silk into early applications that require little material, such as biocompatible artificial tendons and ligaments, thin, biodegradable sutures for eye surgery and other delicate operations, and high-strength fishing line. Down the road, Nexia plans to transfer the genes to the mammary cells in goats, in hopes that the proteins can be harvested from the milk. That, in turn, could produce silk proteins in plentiful quantities for applications such as high-strength composites and soft, flexible bulletproof clothing for soldiers and police—all without the chore of figuring out how to raise spiders on a farm.

4. CELL BIOLOGY

# Stripping the Nucleolus Down to Its Proteins

1. Jennifer Couzin

The human genome may be the mother of biological blueprints, but it's spawning plenty of offshoots: more modest lists of molecules powering often crucial bits of cells. The latest such roster—271 proteins identified in a compartment of the cell nucleus called the nucleolus—is a first step toward fully deciphering this organelle, a critical element in the construction of ribosomes, which go on to make proteins. With scientists now debating the nucleolus's role in additional functions, including cell cycle regulation and gene silencing, this starter list of proteins—30% of which are uncharacterized—offers plenty to chew on.

To assemble the protein map, the largest ever reported for a single organelle, cell biologists Angus Lamond of Scotland's University of Dundee, Matthias Mann of the University of Southern Denmark in Odense, and their colleagues at both institutions melded a decades-old method with cutting-edge technology and the latest human genome data. Applying an updated version of a 1960s technique, they treated human nuclei with sugar and sound waves and, using a centrifuge, separated the relatively dense nucleolus from its gelatinous home in the nucleus. Mass spectrometry combined with searches of human gene databases enabled the biologists to identify and characterize what they found.

“It's like being in a candy store: They've got all these wonderful proteins,” says Joseph Gall, a cell biologist and staff member of the Carnegie Institution of Washington's branch in Baltimore, Maryland. Still, he and others caution that painstaking research lies ahead. “It is a framework for future work,” says Tom Misteli, a cell biologist at the National Cancer Institute in Bethesda, Maryland. “But it doesn't really answer any single question.”

As Lamond and his colleagues report in the 8 January issue of Current Biology, 191 of the proteins have been characterized, and over half of them share links to the nucleolus, adding a layer of certainty to past research. This set includes various ribosome builders, as well as other proteins that process and transcribe ribosomal RNA, a necessary step before the ribosomes can be assembled and pushed out of the nucleolus.

The remaining 90 or so characterized proteins participate in a hodgepodge of functions. They include molecular chaperones, which prevent other proteins from sticking together; translation machinery, which coaxes messenger RNAs and ribosomes to form proteins; and so-called DEAD-box proteins, which control the structure of RNA. “The actual overall complexity of the nucleolus was somewhat surprising,” says Lamond, who suspects that it's far more than a ribosome factory.

That's likely to be the case, cell biologists agree. But the British and Danish team's list may also include non-nucleolar, contaminant proteins, say Gall, Misteli, and the researchers themselves. Without a membrane, the nucleolus is notoriously difficult to separate from the nucleus, and even the purest sample could contain molecules that accidentally stuck to it during the split. In addition to those that may have erroneously made the cut, several dozen known ribosomal proteins are absent from the roster; Lamond agrees that more nucleolus proteins remain to be found.

Nevertheless, biologists believe that only by paring down the nucleolus to its biochemistry can they read its part of the script. Surprises are expected.

5. MILITARY RESEARCH

# Army Ordered to Hunt Down New Technology

1. David Malakoff

Congress has ordered the U.S. Army to be all that it can be to promising high-tech start-up companies. Lawmakers have given the Army $25 million to establish an independent venture capital fund that will take an ownership stake in companies with promising military technologies. The unusual approach is drawing good reviews from some analysts. But some of the Army's own science advisers doubt that it can succeed, much less ever turn a profit. The new venture fund is included in a$317 billion defense spending bill signed last week by President George W. Bush. It's aimed at shaking up a $1.2 billion Army R&D program that critics say has been too slow to deliver battlefield advances, from lighter weapons to better communications systems. The Army is also accused of relying on a few well-established defense contractors and overlooking smaller companies with better ideas but less political clout. “There is a bit of the hardening of the arteries over there,” says Greg Dahlberg, acting Secretary of the Army under President Bill Clinton and now a top Democratic staffer on the House Appropriations subcommittee that oversees the Pentagon. To help unclog the Army's technology pipeline, Dahlberg and other fund supporters have borrowed an idea from the Central Intelligence Agency (CIA). In 1998, the CIA set up In-Q-Tel, an independent venture capital fund that has since funneled nearly$50 million into several dozen youthful information technology companies. The fund looks for firms that can both produce promising new intelligence tools and turn a healthy profit selling products to other consumers, and it sometimes takes a stake in the company. Eventually, the federal investment is supposed to generate enough income to make the fund self-sustaining.

Although In-Q-Tel is still far from breaking even, last year an outside review panel praised its contribution to modernizing the CIA and told Congress to continue funding it. The $25 million in start-up cash for the new fund will come from an across-the-board tax on the Army's basic and applied research budgets, although legislators fenced off several dozen projects deemed essential. Army officials have already begun to assemble a wish list of technologies to guide fund managers—to be recruited from government and the private sector—in their search for “those nimble young companies that don't usually deal with the Army but have a lot to offer,” says Army chief scientist A. Michael Andrews II. One potential pool of candidates, he notes, will be the several hundred researchers who have won recent grants from the Army's small business development program. This month Andrews and others will begin to wrestle with a slew of organizational issues, including whether to establish the fund as a new entity led by a seasoned executive (like In-Q-Tel) or to ask an existing outfit to manage the$25 million pot. Officials appear to favor the In-Q-Tel model but not its estimated 15% administrative costs. “I'm looking to hold down the overhead,” Andrews says.

Whatever model is chosen, some analysts question whether the Army's venture into high-tech investing can pay off. Last year, for instance, an Army Science Board panel concluded that existing research funding mechanisms could meet the Army's needs. It also warned that creating a venture fund could embroil the Army in “tumultuous” debates over how to spend any potential income. But it questioned whether products made for the military will also be attractive to other consumers; the Army now earns less than $500,000 a year in royalties from products it helped develop, the panel noted. Such concerns, however, don't worry the fund's backers. Although Dahlberg says he doesn't expect the fund “to change the world, it will help get [the Army] closer to the creative smaller organizations.” House appropriators, he adds, are ready to boost its annual budget, to up to$50 million, if things go well over the next few years. Success could also mean spreading the concept to the other armed services.

6. ASTRONOMY

# Star-Spangled Universe Dawned in Early Light

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Utrecht, the Netherlands.

Hollywood directors would have filmed it differently, but Mother Nature started her performance with the grand finale. A few hundred million years after the big bang, long before anyone was around to appreciate the spectacle, the universe blazed with the most violent burst of star formation it has ever experienced. Since then, the rate of star formation has decreased, and the current activity is just a fizzle compared with the natal fireworks.

That new screenplay contradicts earlier scripts, which suggested that star formation gradually increased until a “baby boom” took place some 4 billion years after the big bang before dropping off again. “All analyses so far have missed a substantial part of the starlight in the very early universe,” says Ken Lanzetta of the State University of New York, Stony Brook, who presented his results at a press meeting at NASA headquarters on 8 January 2002. A paper describing the new theory will soon be published in The Astrophysical Journal.

To learn about the early universe, astronomers examine very distant galaxies, whose light took billions of years to reach Earth. Three tiny patches of sky, known as the Hubble Deep Fields, have been studied in exquisite detail, both by the Hubble Space Telescope and by other instruments in space and on the ground. But according to Lanzetta, “even the deepest images made by Hubble are not sensitive enough to detect most of the light in the very distant universe.” As a result, astronomers can glimpse only a small fraction of the amount of star formation in distant galaxies. “At these large distances, our telescopes see only the brightest parts of the galaxies,” Lanzetta says. “The faint and intermediate-bright parts are below the observational threshold. But it's the intermediate-bright parts of galaxies where most of the starlight is being produced.”

To calculate how much of that light had dropped below the range of visibility, Lanzetta and his collaborators analyzed all available observations of the Hubble Deep Fields. For some 5000 faint galaxies, they first determined their distances by studying their colors. More-distant galaxies appear redder because their light has been stretched more by the expansion of the universe. Then the astronomers calculated how much energy was produced in each pixel of the images. By comparing these results with data from nearby galaxies, the team was able to estimate how much starlight earlier analyses of the Hubble Deep Fields had missed—like a listener reconstructing the repertoire of a distant marching band by comparing recorded music with the booming of the bass drum. Lanzetta's technique “is really very nifty,” says Bruce Margon of the Space Telescope Science Institute in Baltimore, Maryland, although he adds that the result will probably be controversial, because the measurements are extremely difficult.

If Lanzetta is right, the new findings have far-reaching implications for ideas about the formation of galaxies, among other things. Many galaxies may have formed early and rapidly instead of gradually, as most cosmologists have assumed. Such a fast-start scenario also would make it easier to explain why the early universe appears to have already been “polluted” with relatively heavy elements, which are produced in stars and then dispersed through space by supernova explosions.

Some astronomers are skeptical. Barry Madore of NASA's Infrared Processing and Analysis Center in Pasadena, California, who hasn't read Lanzetta's paper yet, says the results might be easier to swallow if there were independent confirmation. In fact, one unrelated study comes up with a somewhat different conclusion. Rodger Thompson of the University of Arizona's Steward Observatory in Tucson carried out a similar analysis using data from the Hubble Space Telescope's infrared NICMOS camera. His results point to a less violent beginning for the universe, with a star formation rate that stayed relatively constant for a couple of billion years before gradually tapering off. Thompson says the discrepancy might be due to subtle differences in the way the two teams corrected for the missing light.

Although Lanzetta says studies of distant quasars support his conclusions, he concedes that his analysis doesn't constitute definitive proof. But he hopes that future instruments such as the Next Generation Space Telescope and the Atacama Large Millimeter Array might see part of the missing light.

7. THERMODYNAMICS

# Quantum Engine Blasts Past High Gear

1. David Voss

All engines, whether the colossal thrusters on the space shuttle or the gasoline-fired power plant under the hood of your car, have to obey the laws of thermodynamics. Among other things, the laws set clear limits on the engines' efficiency: how much work they can squeeze from a given energy input. But take those classical axioms and add quantum mechanics, and unusual things can happen. Recently, Marlan Scully, a physicist at Texas A&M University, College Station, has discovered that in the quantum world, you can sometimes reap more horsepower than you'd expect.

Scully found that in theory he could take the hot exhaust from one kind of heat engine and drive a laser with it. Lasers work by storing energy in the internal quantum energy states of atoms or molecules and then releasing the energy in the form of photons. But heat engines generally ignore the internal states and instead harness the thermal motions of atoms and molecules in the “working fluid” (for example, the hot gas made by burning gasoline) as it expands and moves pistons to turn a crankshaft. The twist in Scully's scheme is to trade energy between the external and internal states of the atoms in a carefully choreographed way so as to squeeze a few more drops of work out of the engine.

In a paper accepted for publication in Physical Review Letters, Scully applies the concept to a type of heat engine called the Otto cycle, a cousin to the common car engine. Scully considers an idealized version of this engine without the exploding gasoline, instead just considering what happens as gas is compressed, is heated, does work, and is cooled again.

In his scheme, Scully takes the still-hot gas in the expanded piston chamber and routes it into a laser cavity, where the internal quantum states of the gas molecules come into play. The hot exhaust that would normally just be shoved out the door gets used to create more useful work by means of the laser emission. As a result, the total energy out is more than you'd expect from classical thermodynamic analysis of an “ideal” Otto cycle engine.

“I think it's a nice paper, very fun, and it's potentially useful,” says Seth Lloyd, a physicist at the Massachusetts Institute of Technology. After hearing Scully give a talk about the concept, Lloyd dubbed the theoretical gadget a “quantum afterburner” by analogy to the devices that squeeze extra thrust out of the exhaust from a jet engine. “It takes advantage of a source of energy that hasn't been taken advantage of before,” Lloyd says. After all, “the steam engine wasn't very useful until James Watt came along and made it more efficient. He didn't invent the steam engine, but he figured out how to control it.”

Scully acknowledges that his analysis is controversial. But he says that doubters who once attacked him for flirting with perpetual motion have come around. “In thermodynamics, the devil is in the details, but so are the angels,” he says. “You have to look at a specific physical system [such as the engine] and not just abstract thermodynamic calculations.” Ronnie Kosloff, a theoretical chemist at Hebrew University in Jerusalem, agrees that Scully's concept is on solid ground: “It is consistent with all the laws of thermodynamics.”

To check that his equations were on the up-and-up, Scully recently put his quantum afterburner to the ultimate theoretical test: hooking it up to an engine running at maximal efficiency. Until then, he had applied it only to the Otto cycle engine, which runs less efficiently than thermodynamics allows. But when Scully probed how well such a device would work with the ideal Carnot cycle, the gold standard of thermodynamic machines, the quantum afterburner couldn't squeeze out any extra energy—proof, Scully says, that his theoretical device is playing by the rules.

8. GEOBACTERIA

# Microbes Use Mud to Make Electricity

1. Elizabeth Pennisi

Self-recharging bacterial batteries that clean up organic pollution as they generate electricity? Sounds more like science fiction than science. But on page 483, microbiologists report coming one step closer to making microbial fuel cells a reality: They harnessed bacteria to generate electricity from underwater sediments. The microbes make excess electrons that they stick directly to graphite wires, which in turn send current to a second wire much like a car battery does. For fuel, the bacteria use organic material in the sea floor. These bacterial batteries will probably never power a car, but they should be adequate to run underwater sensors, says Derek Lovley, a microbiologist at the University of Massachusetts, Amherst, who with Daniel Bond led the work on these unusual energy sources.

Because organic sediments are so abundant, “theoretically there could be an inexhaustible source” of fuel, Lovley notes. And because many pollutants are organic, these portable generators might also help get rid of hazardous materials. “The whole field is very exciting,” says Greg Zeikus, a microbiologist at Michigan State University in East Lansing, because the work has broad potential for both helping pollution cleanup and providing a cheap power supply. “This work has come closer to developing accessible marine batteries as a way to meet our electricity needs.”

Lovley's team was not the first to notice that microbes could steal electrons from oxygen-deficient mud and somehow transfer them to electron-accepting rods placed into the oxygen-containing sediments overhead. But now, Lovley and his colleagues “take a concept that has been known for a while and make good on it,” says Diane Newman, a microbiologist at the California Institute of Technology in Pasadena.

The team used lab fish tanks to recreate the ocean's saltwater environment. Collaborator Leonard Tender of the Naval Research Laboratory in Washington, D.C., positioned graphite wires (which act as electron-accepting anodes) into oxygen- deficient sediments collected from the sea floor. Then he placed graphite wires (the cathodes) in the overlying oxygen- containing water to receive electrons. In three different experiments, the team measured the number of electrons transferred to the anode and then to the cathode. Even in these crude experiments, the current was enough to power a small calculator, the scientists report.

After several weeks, the researchers identified the microbes that were growing on the mud-implanted electrodes. To their surprise, Lovley and his colleagues found that one type of microbe—Desulfuromonas acetoxidans, from a family called Geobacteraceae—had all but taken over the battery electrode, ousting the others. These geomicrobes are famous for their ability to detoxify toluene and other organic solvents, notes microbiologist Caroline Harwood of the University of Iowa in Iowa City.

Previously, microbiologists had shown that different microbes could move electrons from oxygen-deficient to oxygen-rich substances through intermediate substances that they produced. “The microbes were involved, but not directly with the electrode,” Lovley explains. But geobacters, as the family is commonly called, need no such go-betweens. They can convert the mud's organic matter directly, and that might prove quite useful in pollution control, he points out.

Before using organic pollutants to fuel electricity production leaves the realm of science fiction, Lovley and his colleagues warn, the work needs to be replicated in field conditions. And Harwood points out that the bacteria might quickly exhaust local organic fuels and have to be moved to a different spot. The efficiency of the transfer also needs improving, something that Lovley and others are fervently working on; otherwise, says Zeikus, it would take fields of electrodes to get enough energy to power many undersea devices.

9. TRANSPORTATION RESEARCH

# Bush Trades Hybrid for Hydrogen Model

1. David Malakoff,
2. Robert F. Service

The federal government's most prominent joint research project with industry moved onto a slower track last week. Secretary of Energy Spencer Abraham announced that he is junking the Clinton Administration's Partnership for a New Generation of Vehicles (PNGV)—an 8-year-old government effort to build superefficient cars—in favor of building vehicles powered by pollution-free hydrogen fuel cells. Abraham released no budget details of the new program, called Freedom CAR (Cooperative Automotive Research), but analysts say most of the old program's research efforts will continue. The deadlines for getting a car on the road, however, have been pushed way back.

In unveiling PNGV in 1993, the Clinton Administration promised to work with major automakers to create family sedans that, by 2004, could go nearly 36 kilometers on a liter of gasoline (80 miles per gallon). But some environmentalists and free-market advocates complained that the program was an industry subsidy that undermined efforts to increase mandated fuel efficiency standards (Science, 30 July 1999, p. 680). The government has spent more than $1 billion on the partnership—including more than$125 million this year—and the big three automakers spent even more.

The results to date have been uneven. In a series of annual reviews, the U.S. National Academies found that the project had made progress in developing lightweight materials and longer lasting batteries, improvements that are being incorporated into hybrid electric-gas vehicles due out within the next 5 years. (Toyota and Honda are already producing such cars.) Fuel cell developers also got high marks for their work on devices that can convert hydrogen into electrical energy, with water as the only byproduct.

But the panels warned that the 2004 deadline for rolling out affordable supercars was unrealistic. And air-quality advocates complained that the power plant deemed the best bet by PNGV engineers, a hybrid diesel-electric engine, wouldn't meet clean air rules. Such problems led the panel last year to call for a serious rethink of the program's structure and goals.

Abraham's answer, announced on 9 January at Detroit's annual auto show, is Freedom CAR. It drops the emphasis on diesel hybrids in favor of PNGV's fuel cell effort, a shift welcomed by many environmentalists. But Abraham drew darts for failing to set deadlines for what he promised would be a decades-long “fundamental research and development” effort. “It remains to be seen how substantive the changes will be, but I'm concerned that we'll give up some important near-term work for benefits that we may not see for decades,” says Dan Reicher, a former Clinton Administration energy official now with the World Resources Institute in Washington, D.C.

The reaction of fuel cell advocates is decidedly more upbeat. “It makes sense,” says Vernon Roan, who heads the University of Florida's fuel cell laboratory in Gainesville and served on PNGV peer-review panels. “The government ought to support high-risk/high-payoff research that is in the national interest.” John Turner, a hydrogen fuel cell expert at the National Renewable Energy Laboratory in Golden, Colorado, agrees: “It's where we ought to be headed.”

Roan and other experts note, however, that the change in name from the unpronounceable to the patriotic (PNGV to Freedom CAR) may be the most noticeable immediate change. Much of PNGV's research agenda is expected to continue under the new program, because fuel cell cars will also need improved materials and better electrical systems, for example. Department of Energy (DOE) officials say the agency spends about $100 million a year on fuel cell research, with about half of that going to polymer exchange membrane cells, the type most likely to be used in cars and trucks. DOE spends another$30 million on hydrogen research, principally looking for efficient ways to generate and store the gas.

Turner calls this budget a start but says it's “small potatoes” compared to what will be needed to get fuel cell cars to market. One major challenge will be replacing the trillion-dollar, gasoline-based infrastructure with a network of hydrogen fuel stations. The cost of a hydrogen future won't be known until 4 February, when the president sends Congress his request for the 2003 budget.

10. PUBLIC HEALTH

# Anthrax Vaccine Begins a New Round of Tests

1. Eliot Marshall

Almost everybody loves to hate the anthrax vaccine. It's old, inefficient, and the cause of many complaints. Indeed, when the U.S. government recently offered to vaccinate thousands of people who may have been exposed to anthrax spores in spiked mailings, only 130 rolled up their sleeves. Many in the U.S. military have also balked at orders to receive six anthrax shots plus annual boosters.

Approved 32 years ago, this vaccine made from a laboratory bacterial culture was designed to protect textile mill workers against skin infections. Now it is being used against inhaled anthrax, and the government is reexamining its safety and efficacy. Since 1999, Congress has given the Centers for Disease Control and Prevention (CDC) in Atlanta $36 million for such studies, responding to complaints from service members and problems at the sole manufacturing plant—owned by BioPort Corp. in Lansing, Michigan. BioPort has been compelled to suspend production since 1998 for safety checks. Researchers planning the CDC studies briefed an oversight panel at the Institute of Medicine (IOM) in Washington, D.C., last week—and got a mixed review. Dennis Kasper, a molecular geneticist at Harvard Medical School in Boston, for example, saw “good progress.” But clinical microbiologist Patricia Ferrieri of the University of Minnesota Medical School in Minneapolis said to CDC scientists: “Forgive the plain language, but you need to get your act together.” It is “urgent,” she said, to move faster on this complex set of studies. One of the most urgent CDC studies is a clinical trial of 1300 volunteers to test the effectiveness of fewer shots (four or five rather than the standard six) and a gentler route of injection (intramuscular rather than subcutaneous). This trial is on hold until the government permits BioPort to resume vaccine production. CDC's Nina Marano said she hopes that CDC can begin enrolling subjects this month. View this table: Jairam Lingappa of CDC's special pathogens branch described a complementary study in macaques that's designed to reveal precisely how much vaccine is needed—and at what intervals—to protect against lethal infections. Researchers have tentatively defined an antibody test to measure the immune response in blood. If CDC finds a way to bridge animal and human data, this could become important for testing future anthrax vaccines. Sixty of a planned 108 monkeys have already received shots, but the trial is now being restructured. While these groups examine efficacy, others are checking on safety and side effects. The CDC's Michael McNeil, for example, reported on an ambitious epidemiological study that will look for long-term effects by focusing on a textile mill “in the U.S. Southeast” that for 30 years required all employees to get anthrax shots. “Even the man who filled the Coke machine got vaccinated,” McNeil said. CDC hopes to get information on more than 1300 of the estimated 2778 people who received nine or more shots, looking at everything from cause of death to self-reported current “energy level” and “cognitive function.” CDC is also planning a survey of military personnel to learn about their attitudes and experiences. It will mine data in military medical records, searching for problems and testing theories. U.S. Army clinical teams will conduct studies of vaccine procedures and adverse events. The IOM panel's main critique of the CDC's large agenda last week was that it had not gelled. Some parts—such as the clinical trial—have been put on hold because of the vaccine shortage. Others were delayed by the terrorist and anthrax attacks, as Randy Louchart of CDC's National Immunization Program explained. Other CDC staffers noted that researchers have been struggling to modify their plans to include suggestions from expert advisers, as the IOM group had urged them to do earlier. During last week's meeting, IOM panel members said they were not sure how they can evaluate CDC's plans—and produce a peer-reviewed report—before the end of the year, as Congress has requested. They urged the CDC scientists to nail down their research agenda before this group meets to put its views in writing at a closed meeting in March. 11. JAPAN # Libraries Seek Ways to Hold Down Costs 1. Dennis Normile TOKYOJapan's university libraries are losing the battle to keep scientific journals on their shelves. Soaring subscription prices, an unfavorable exchange rate, and a decentralized approach to collections have led to a dramatic reduction in the number of available titles at the country's 99 national universities. But library officials haven't given up the fight. Last week they met here to discuss taking advantage of cheaper online access and using their joint bargaining power to bring down subscription costs. Japan's library crisis parallels the problems facing U.S. and European institutions (Science, 30 October 1998, p. 853). Although the government has steadily boosted spending on science and technology throughout the 1990s, most of the money has gone into competitive grants. The country's two 5-year science plans, for example, contained “no mention of scientific and scholarly communication,” says Syun Tutiya, a professor of information sciences and director of the library at Chiba University, east of Tokyo, who helped organize the 9 January symposium. The problem has been exacerbated by a steady decline in the value of the yen against the dollar and most European currencies, making foreign periodicals ever more expensive. As a result, the number of titles received by the national libraries has dropped by half since peaking at 40,000 in 1989. But Japan's libraries also face a host of institutional challenges. Many journals are ordered not by the library but by individual professors, using research funds. And those subscriptions may be canceled at any time. The result can be both multiple subscriptions and sudden gaps in a library's collection. In addition, many individual departments have their own libraries, which typically are not accessible by outsiders. All these factors, says Tutiya, means “we really don't know the extent of our journals crisis.” Even so, there is consensus that the biggest challenge is rising subscription prices. Individual universities traditionally have purchased material through subscription agents and have had little or no direct contact with publishers. However, last year a consortium of national university libraries negotiated discounts and package deals with Europe-based Reed Elsevier and several other major academic publishers. Although nondisclosure clauses prevent Tutiya from providing details, he acknowledges that “it is a discount.” Library officials hope to extend the consortium approach to online journal access. An advisory panel to the Ministry of Education, Culture, Sports, Science, and Technology is finalizing recommendations likely to lead to funding later this year for site licenses that provide online access to journals. The idea is to negotiate agreements with journal publishers involving faculty, staff, and students at some 70 national universities, says Jun Adachi, a member of the working group drafting the recommendations and an information scientist at the National Institute for Informatics (NII), which hosted last week's symposium. Meeting participants also heard from Alison Buckholtz, associate enterprise director for the Scholarly Publishing and Academic Resources Coalition (SPARC), a library advocacy group based in Washington, D.C. “There has been a lot of interest in our ideas for online journals and alternatives to commercial journal publications,” says Buckholtz. NII is expected to play a major role in advocating similar reforms, because Japan's national university libraries are not allowed to spend money to join an advocacy organization such as SPARC. Tutiya sees last week's meeting as the first step in getting libraries to develop a strategy for coping with the changes sweeping through academic publishing. Such a plan, he and others say, would be an essential ingredient in convincing government officials that Japanese academic libraries need help. 12. TAIWAN # Frank Shu Named University Head 1. Dennis Normile* 1. With reporting by Robert Irion. Frank Shu, an astronomer at the University of California, Berkeley, is coming home—for the first time. Next month Shu becomes president of Taiwan's National Tsinghua University, Hsinchu, adding to the list of prominent ethnic Chinese scientists from abroad who hope to build Taiwan into a scientific and technological powerhouse. “His coming to Taiwan is quite a coup for the academic community here,” says K. Y. (Fred) Lo, director of Academia Sinica's Institute of Astronomy and Astrophysics in Taipei. Shu, 59, was born in the southern China city of Kunming but as a child moved to the United States with his family. Trained at the Massachusetts Institute of Technology and Harvard University, he joined the Berkeley faculty in 1973 and in 1998 was named one of a handful of University Professors. Although Shu has never lived in Taiwan, he will be following in the footsteps of his father, Shien-siu, who led the university in the early 1970s and later helped create Hsinchu Science Park, Taiwan's “Silicon Valley.” He is also emulating Lee Yuan-tseh, a Taiwan native son and 1986 chemistry Nobelist who left Berkeley in 1994 to become head of Academia Sinica, and dozens of prominent scientists whom Lee has recruited. Astronomers praise Shu's theoretical work on the structure of spiral galaxies and, more recently, on star formation. “He has played a leading role in making star formation a major field,” says Anneila Sargent, a radio astronomer at the California Institute of Technology in Pasadena and current president of the American Astronomical Society, which Shu headed in 1995. Shu says he decided to take the job “because I realized I can make a bigger difference in Taiwan than by remaining in the United States.” But he admits he faces some significant challenges in raising the quality of Taiwan's universities. In addition to tapping private sources to supplement government funding, Shu also hopes to change a culture in which resources are shared equally to one in which academic stars receive the support they need to shine. “There is a growing understanding [among government officials] that science at the forefront is an elitist affair,” he says. 13. CENTRAL ASIA # Caspian Ecology Teeters On the Brink 1. Richard Stone As nations around the world's largest lake bicker over oil rights, the wildlife of the Caspian Sea is in a state of siege from which it may never recover ASTRAKHAN, RUSSIALev Khuraskin stepped gingerly across the shoal, avoiding the dead seagulls and cormorants rotting in the sand and their squawking, orphaned chicks. The rail-thin biologist, his face leathered from decades on the sun-drenched Caspian Sea, crept up to a seal lolling near the water and straddled it, pressing his hand against the back of its neck to subdue it as a colleague skittered over to draw blood. Fit seals don't like being messed with, but this emaciated and listless male submitted calmly. “It's very ill,” says the team's leader, Vladimir Blinov of VECTOR, Russia's State Research Center of Virology and Biotechnology. The seal that lay dying on Malyi Zhemchuzhnyi Island is one of the latest casualties in the Caspian Sea's unfolding ecological drama. Sturgeon, prized for their caviar, are hovering near enough to oblivion that three of the five nations around the Caspian's shores—Azerbaijan, Kazakhstan, and Russia—agreed last June to an unprecedented 6-month ban on fishing the species. Too little, too late, some fear. “The question is whether the species can be saved at all,” says Lisa Speer of the Natural Resources Defense Council (NRDC), a nonprofit based in New York City. Adding to the mounting horror of ecologists, Mnemiopsis leidyi, a comb jelly notorious for having devastated anchovy populations in the Black Sea, invaded the Caspian a few years ago. New findings suggest that this voracious free-floater has done a similar number on the Caspian's kilka, or sprat, by “driving numerous species of zooplankton toward extinction,” says ecologist Henri Dumont of Ghent University in Belgium. Mnemiopsis is more bad news for the seals, which feed on kilka and are already reeling from epidemics of canine distemper virus in 1997 and 2000 that killed thousands. If the Caspian's wildlife only had natural invaders to deal with, that would be bad enough, but this lake—the largest in the world—is a pressure cooker of political and commercial forces. Ranged around its shores are the growing economy of Russia in the north and fundamentalist Iran in the south, with Muslim ex-Soviet republics in between. Both Russia and the United States are vying for influence in the region, a process accelerated by the war in nearby Afghanistan. Complicating the picture are the Caspian's vast oil reserves. The Soviets largely ignored this resource, but the newly independent republics are keen to exploit it. Production in the Caspian is expected to ramp up fivefold to 5 million barrels a day by 2020. “For the time being, there's no proof that oil exploration or extraction will pose a major hazard to the Caspian environment—if it's done properly,” says Arkadiusz Labon, a Toronto-based fisheries consultant who coordinated a major fish stock survey in the Caspian last year. However, he and others note, a major spill—always a possibility in this geologically unstable region (see sidebar)—could spell disaster. ## Oil in troubled waters Two millennia ago the Caspian was a sacred place for Zoroastrians, who would meditate at temples near jets of flaming gases that vented from the naphtha-rich sands of the Apsheron Peninsula, a nub of land jutting into the Caspian in present-day Azerbaijan. Later generations of Persians, still awestruck by the pillars of fire, recognized a commodity and by the late 1500s were scooping petroleum from shallow wells. True development of the oil fields began in 1875 when Ludvig and Robert Nobel, brothers of renowned Swedish industrialist Alfred, bought up land near Baku. Boring deeper wells, they and their crew learned how to work Apsheron's fickle semifluid sands. Oil production increased by 50 times over the next decade, reaching 1 million tons a year. When after a brief independence Azerbaijan was absorbed into the Soviet Union, the Nobels were out and central planning was in. Although the Soviets discovered three giant oil fields in the Caspian basin, they left them mostly untapped. They found it easier and less costly to extract oil from their vast petroleum reserves in western Siberia and even went as far as banning offshore drilling in the north Caspian to protect the sturgeon's feeding grounds and spawning migration routes. Following the collapse of the Soviet Union, oil investments from the West poured into the Caspian, turning the region into a “Wild East.” But although oil exploration has not yet had a major impact on local ecology, the same cannot be said for fishers out to make a fast buck by harvesting the Caspian's other precious resource: caviar. ## Of fish and jellyfish With their long snouts and ridged, scaleless bodies, the young sturgeon swimming circles in a glass tank at the Caspian Fisheries Research Institute here in Astrakhan look more like baby dinosaurs than fish. But having long outlived the dinosaurs since debuting in the fossil record 200 million years ago, the venerable sturgeon is facing its toughest test yet. The Caspian is home to the world's biggest population of sturgeon. The sea's four major varieties—stellate sturgeon, or sevruga (Acipenser stellatus), Russian sturgeon (A. guldenstadti), Persian sturgeon (A. persicus), and beluga (Huso huso)—supply about 90% of the total caviar harvested worldwide. It's a lucrative commodity: As Science went to press, one firm, Tsar Nicoulai Caviar, was advertising sevruga caviar at$1448 per kilogram. Beluga roe, meanwhile, was fetching more than $2500 per kilogram. Russia alone says it hauled in$40 million last year from caviar exports, although some observers claim that the figure for legal exports was closer to $100 million. The sturgeon's enemies are legion, but poachers may be taking the heaviest toll. Last year they fueled a shadow caviar market estimated at$400 million, according to Russia's Interior Ministry. Rampant poaching since the Soviet meltdown has sent sturgeon stocks crashing, with beluga numbers less than 10% of what they were 2 decades ago, the government estimates. Last year Russia began working with Interpol to try to crack down on smuggling, but most observers say it will take years, if not decades, to stamp it out. Other factors in the decline include dams on the Volga River that cut off access to spawning areas, and perhaps pollutants that accumulate in fat and may render eggs infertile. “The whole ecology of the rivers has changed,” says biologist Ellen Pikitch of the Wildlife Conservation Society in New York City.

Recognizing the seriousness of the situation, the secretariat of the Convention on International Trade in Endangered Species (CITES) got three Caspian nations to agree to a 6-month moratorium on fishing sturgeon last June. Some experts contend that the ban, which ended on 1 January, did little good for the sturgeon, because it took hold after the main fishing season in the spring.

A recent census of Caspian fish corroborates that view. Last summer, the Caspian Environment Programme (CEP), a World Bank and European Union initiative, undertook a rare comprehensive survey of Caspian fish stocks. Over 6 weeks last August and September, the CEP team used sonar to chart and characterize fish populations everywhere but in the coastal waters of Turkmenistan, which did not allow access. Sonar is an imperfect technique, particularly for bottom-feeding fish like sturgeon, so the team captured and released fish as well.

Although the researchers are still analyzing their data, the emerging picture is dire indeed. “We found very few mature sturgeon,” says Labon. “That's a sure sign of dramatic overfishing.” As expected, the team found ample young sturgeon, indicating that hatcheries in the Volga delta and Iran have averted total calamity. But the hulking fish are late breeders, taking years to reach sexual maturity. That means poachers and other fishers will be netting more and more juveniles in an increasingly frustrating search for caviar.

Labon argues that a 10-year fishing ban—without loopholes such as a permissible “scientific” catch—is essential to rescue the sturgeon from extinction. However, a total moratorium could backfire by driving the entire caviar trade underground, argues NRDC's Speer. Her organization, for one, is campaigning for a ban on trade of beluga only, the most endangered species. It will make that pitch when the CITES standing committee on sturgeon meets in March to review this year's proposed catch quotas. NRDC will also lobby the next conference of CITES parties in November to elevate beluga to the most endangered Appendix One list, which would ban beluga export from any signatory nation.

The sturgeon is not the only Caspian fish under siege; some other species are facing a more insidious, if spineless, threat. First sighted off the Iranian coast in 1998, the comb jelly Mnemiopsis within months had managed to swarm across much of the rest of the Caspian. The delicate, luminescent creature, looking more like a miniature starship than an animal, appears to have stowed away in the ballast water of ships in the Black Sea, reaching the Caspian via the Volga-Don Canal.

Based on the jelly's voracious habits in the Black Sea, researchers expected it to gulp its way through the bottom of the Caspian's food chain, grazing on zooplankton that are the staple of kilka and many other fish. Over the past couple of years, says Labon, professional fishers along the Caspian have been asking, “Where have all the kilka gone?” In Iranian waters, Ghent's Dumont adds, “they don't catch anything but jellies now.” The CEP fish survey spotted this decline. According to Labon, the survey found that kilka and herring populations “are severely depressed” compared to 2 years ago. His team is still crunching numbers to determine precisely how much these fish have declined.

A kilka crash is bad news for the fishing industry in Iran, where there's a big market for the sprats. But for the beleaguered seals that feed on kilka, it could be a crushing blow.

## Hunting a killer

It has been a tough few years for the Caspian's seals. Two years ago, a mystery epidemic killed several thousand of them, including many young ones. A CEP seal ecotoxicology team, led by Susan Wilson of the Tara Seal Research Centre in Northern Ireland, and the VECTOR group—working independently—unmasked canine distemper virus as the likely villain (Science, 22 September 2000, p. 2017). When seals began dying in droves again last spring, both teams headed out to different parts of the Caspian to find out why.

Their preliminary, unpublished findings suggest that canine distemper is not the seals' only foe. After sampling dead or dying seals washed up on the Apsheron Peninsula, Wilson's team found that—unlike what they had observed in 2000—the victims were mostly adults. Analyzing tissue back in the lab along with samples from Iran and Turkmenistan, Wilson and her team so far have found no sign of canine distemper or any other virus.

Wilson's team believes that pollution may be a contributor to last year's die-off. The researchers are now testing their samples for levels of the pesticide DDT and other long-lived pollutants. Such chemicals are also the prime suspect in the seals' plummeting birthrate, says Wilson. But she and her colleagues are pursuing other lines of inquiry, including bacterial infections and poor nutrition.

The VECTOR team's findings add more intrigue. Blinov's group says it detected a flu strain last spring, similar to one that jumped from birds into people in Hong Kong in 1997, in some of the dead seals they had sampled in 2000, as well as a nearly identical strain in a single sick seal in Russia's Lake Baikal. “If avian viruses could overcome host barriers and infect humans in Hong Kong and cause pandemic outbreaks in seals,” says Blinov, “we thought, 'What might occur tomorrow?'” Tests for virus in seals sampled last year on Malyi Zhemchuzhnyi Island are still under way, but they have come up negative so far.

That jibes with the CEP ecotox findings, but it fails to penetrate the mystery of where canine distemper is lurking, or whether the avian influenza that VECTOR spotted was a red herring or a continuing threat to the seals. Wilson speculates that canine distemper, at least, could reemerge in a couple of years. She notes that the evidence is looking more solid that distemper was behind a mass die-off in 1997 and may periodically afflict Caspian seals.

If canine distemper does resurface next year, the seals could be in for a double whammy. Both the CEP and VECTOR teams have reported that many ill or dead seals were underweight and some were emaciated, which may point to a food shortage. Wilson carried out a limited survey of seal feces collected on Apsheron last year and found that kilka appeared to make up only a tiny proportion of their diet, suggesting that the seals had to make do with less-nutritious prey. “We need to extend these diet studies,” Wilson says. But it does seem to bear the tentacle-marks of Mnemiopsis.

Dumont and other experts argue that steps must be taken quickly to rein in Mnemiopsis. After Mnemiopsis levels in the Caspian last fall exceeded those ever reached in the Black Sea, a scientific advisory committee called on littoral nations to approve plans to unleash a predator this spring to control the invader. Their choice was Beroe ovata, a heftier comb jelly that dines almost exclusively on Mnemiopsis. Beroe slipped into the Black Sea in 1997 and quickly brought the villain to heel. There, Mnemiopsis populations had plunged so low by last year that it was hard to find specimens for analysis. Beroe, says Dumont, “is almost too good to be true.”

Azerbaijan and Iran are pressing hard for Beroe to be introduced, but it's unclear whether the other Caspian governments will climb aboard. Signs look unfavorable for agreement on something as contentious as biological pest control—no matter how benign Beroe would appear—when tensions are already running high over oil rights.

## Political hardball

Like 49ers staking claims in California, the five littoral nations have asserted overlapping territorial claims in the Caspian itself. Last summer, Iranian gunships chased an Azeri research vessel out of waters claimed by both countries. A meeting planned for last October at which the countries had agreed to demarcate borders was abandoned after the 11 September terror attacks, although the leaders of Azerbaijan and Turkmenistan are scheduled to visit Moscow later this month in part to revive the negotiations.

The Caspian nations are playing hardball because their oil is considered a major prize by Western powers. The newly independent states could act as a counterweight to OPEC, because the Caspian oilfields would greatly augment the few reserves—including Siberia and the North Sea—not controlled by the Middle East-dominated cartel. Caspian oil “can offset [OPEC's] efforts to keep prices high and their use of high prices for political dictates,” says Brenda Shaffer, research director of Harvard University's Caspian Studies Program.

Apart from Russia, the three countries with the largest Caspian reserves—Azerbaijan, Kazakhstan, and Turkmenistan—have welcomed alliances with the West, which they think will help them convert their black gold into cash and limit Russian influence in their affairs. Beyond oil and gas, the region is important to the United States, which “needs to develop friends like Azerbaijan and Kazakhstan in the Muslim world, due to their clear separation of religion and state,” says Shaffer. Russia, meanwhile, has bolstered its sphere of influence by strengthening ties with Iran and forming alliances with other ex-Soviet littoral states.

Sound like a powder keg waiting to be lit? Quite so, says Terry Adams, a senior associate at Cambridge Energy Research Associates and founding president of the Azerbaijan International Operating Company oil consortium: “The seeds of future Caspian conflict were planted early.” And with an international effort to safeguard the Caspian's ecology nowhere in sight, the lake itself can only suffer in the process.

14. CENTRAL ASIA

# Pillars of Fire, Poison Gas--and Gobs of Oil, Too

1. Tim Burnhill*
1. Tim Burnhill is a freelance writer in Saffron Walden, U.K.

The Caspian's geopolitical stardom belies its humble origin 10 million years ago as a brackish, landlocked remnant of the long-gone Tethys Sea. Born in an era of violent tectonic activity, the Caspian remains a seismic hot spot today where oceanic crust creeping northward thrusts beneath continental crust underlying the Caspian's upper basin. The result is a hellish seascape, wracked by earthquakes and riddled with hydrocarbon seeps and mud volcanoes, that poses a huge challenge for oil extraction—and offers loads of scientific puzzles. “To say the geology is well understood is far from true,” says geologist Mike Simmons, managing director of CASP, a research institute in Cambridge, U.K., that has done extensive fieldwork in the Caspian.

One complex phenomenon that scientists are still trying to fathom is the Caspian's wildly varying sea levels. Levels had dropped so low about 5.5 million years ago that the lake shriveled to little more than a desert puddle in its southern basin. “It must have been a bizarre and unique environment,” says Simmons. Unstable sea levels continue to be a hallmark, rising more than 2 meters between 1978 and 1994 followed by a steady decline since. Fluctuations in evaporation rates and the flow of the Caspian's tributaries can only partly explain sea-level dynamics.

A peculiar topography presents its own set of challenges for both the sea's denizens and oil companies. The Caspian is only 10 meters deep on average in the stable northern basin, but it reaches more than 1 kilometer in depth in the southern basin. Thanks to “one of the most rapid subsidence rates known on the planet,” Simmons says, sediments reach a whopping 25 kilometers thick in parts of the southern basin. As new sediment piles up, water trapped in the clayey lakebed comes under crushing pressures. The clays flow like pressurized fluid, moving upward through fractures in the sediment. The mud escapes from cones—"mud volcanoes”—that can grow so tall that they form islands in the deep waters. Geologists take a keen interest in what mud volcanoes can reveal about the Caspian's underbelly, as the cones disgorge rock from many kilometers deep. “They provide us with precious data,” says Simmons.

The majority of the Caspian's 220 mud volcanoes burble meekly. But a few should not be messed with. Last October, for instance, a cone erupted violently south of Baku, sending muck, rocks, and flaming gases dozens of meters into the sky—the ancient Zoroastrians' pillars of fire. In 1959, one monster on the Markarov Bank reportedly shot flames and debris an astounding 10 kilometers into the air and gouged a half-kilometer-wide crater in the lakebed. “You cannot predict when they are going to erupt,” says geophysicist Mike Bilbo, British Petroleum's Caspian external affairs chief. Drill rigs can't sit too close to the mud volcanoes, which destabilize the lakebed around them—as the Soviets discovered after losing several rigs.

The North Caspian is no less daunting. The oil there is also under high pressure, and it's sour: It's mixed with poisonous hydrogen sulfide gas. “The technical problems are immense,” says Gregory Ulmishek of the U.S. Geological Survey in Denver. “But so is the prize,” he says: an estimated 23 billion barrels of oil yet to be discovered.

Oil firms and ecologists alike dread an accident in the newly discovered Kashagan field off Kazakhstan, which could release tons of hydrogen sulfide into the shallow northern waters. Such an ecological nightmare could overshadow the decades of leaks and spills from the South Caspian's Soviet-era wells, some of which are still pumping crude oil. At these operations, says Bilbo, “there are no work practices that are recognized in the West in terms of environmental controls.”

But often it doesn't take a human hand to unleash the Caspian's malignant forces. The region's natural hydrocarbon seeps “may have an important role in causing water and air pollution,” notes Casey Moore of the University of California, Santa Cruz. Natural seepage, he says, “may be erroneously attributed to human sources”—just one of many features of the unruly Caspian that elicit wonder and are impossible to tame.

15. INFECTIOUS DISEASE

# New Weapons in the Battle of the Bugs

1. Dan Ferber

CHICAGO—Postponed from its original late-September schedule following 11 September, a meeting* on infectious diseases sponsored by the American Society for Microbiology finally convened here last month. Two families of potential antibiotics had attendees talking, and one team presented a possible treatment for the deadly tropical Chagas disease.

## Giving Chagas the Kiss-Off

You may call it just a kiss, but a quick peck from a kissing bug can mean big trouble. The cockroach-sized insects spread the parasite that causes Chagas disease, also known as American trypanosomiasis. Left untreated, the infection lingers for decades, causing devastating heart and intestinal problems that kill 50,000 people a year. No effective drugs exist for the more than 16 million people, most of them poor people in Central and South America, who have chronic infections. But a new strategy, so far successful in lab dishes, aims to stop the parasite in its tracks.

The approach, presented by Julio Urbina of the Venezuelan Institute for Scientific Research in Caracas and his colleagues, blocks the parasite from making ergosterol, a fatty, cholesterol-like molecule that the parasite needs to keep its cell membranes working properly, among other key functions. “It's a very promising target,” says parasitologist Juan B. Rodriguez of the University of Buenos Aires, Argentina.

The kissing bug emerges at night from thatched roofs and cracks in the walls of adobe houses. It bites sleeping people and defecates on their skin, depositing the parasite. When people scratch the bite or touch their eyes or mouth, the parasite, a protozoan called Trypanosoma cruzi, enters its victim. Others are infected from their mothers at birth or when nursing, and still others receive transfusions of contaminated blood.

In the past decade, South American governments and the World Health Organization have funded a campaign to cut Chagas transmission by plastering walls, spraying insecticide, and pushing blood banks to screen for the parasite. The campaign has been remarkably effective, but new drugs for Chagas disease are still desperately needed for the millions who are already, or will become, infected. The two drugs used today to treat acute cases have severe side effects, and they can't touch parasites that have burrowed into the heart and intestine of chronically infected patients.

To find a new Chagas drug, Urbina's team focused on compounds likely to cripple key parasite enzymes. Like other researchers in developing countries working on diseases that afflict the world's poor, Urbina and colleagues tested hand-me-down drugs developed by pharmaceutical companies for other conditions. In earlier work, the Venezuelan team had tested several antifungal drugs that blocked ergosterol biosynthesis. One such drug appeared to rid mice of both the acute and chronic infection (Science, 16 August 1996, p. 969). That research continues, but the antifungal drugs have yet to prove themselves in clinical trials on Chagas patients.

This time the researchers turned to a fledgling anticholesterol drug developed by AstraZeneca in London. In both people and parasites, the compound, abbreviated BPQ, blocks an enzyme called squalene synthase. This in turn blocks cholesterol synthesis in humans and ergosterol synthesis in trypanosomes.

In laboratory cultures, Urbina reported, low doses of the compound killed a free-living form of the parasite, called the epimastigote. And it mowed down the most dangerous form of the parasite—the amastigote, which infects human heart and intestinal tissue—as it grew inside cultured monkey kidney cells. The drug spares host cells, probably because they replace missing cholesterol from their surroundings, but it kills the parasites, which can't replace their ergosterol, Urbina says.

“It's very interesting and good work, but it's very early on,” says Louis Kirchhoff of the University of Iowa, in Iowa City, who notes that the drug has yet to be tested in animals or humans. But for chronic Chagas disease, he adds, there are not a lot of alternatives.

## Antibiotic Contenders

As antibiotic-resistant superbugs spread worldwide, researchers have stepped up the hunt for new drugs to fight them. It's been difficult: In the last 3 decades, just one new class of antibiotic has made it to the clinic. At the meeting, researchers described two new contenders that kill drug-resistant superbugs, one in animal tests and one in lab cultures. If they hold up under further testing, the compounds could one day offer an edge in the ongoing arms race against the most dangerous of bacteria.

Almost all of today's antibiotics use one of three strategies. They block microbes from assembling a cell wall, manufacturing new proteins, or copying their DNA. As bacteria evolve ways to outwit these strategies, new targets are urgently needed.

One possible target is the bugs' DNA. Roland Bürli and his colleagues at GeneSoft Inc. in South San Francisco, California, have been trying to improve upon a well-studied class of synthetic compounds, some of which can kill bacteria by binding to their DNA. GeneSoft's team engineered compounds called heteroaromatic polycycles (HARP); these compounds nestle into DNA at specific sequences called promoters that flank genes and control their expression. Once there, the compounds stop the microbes from activating genes. They also bind sequences used by DNA replication enzymes, which interferes with bugs' ability to copy their genome.

To test the compounds' power, the team screened 200 versions against three nasty bugs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae. Four of the 200 compounds killed the bugs at relatively low doses. By binding to promoters, the four compounds prevented the bacteria from transcribing key genes, according to results from another GeneSoft team headed by James Ge.

One looming hurdle remains in the drugs' way: Human DNA could be disrupted by such compounds as well. To demonstrate that the compounds can be made specific to bacteria, Bürli's team tweaked them so they killed bacteria but not yeast, whose chromosomes resemble those of human cells.

The HARP compounds “have the potential to be a real drug,” says Jianshi Tao, director of molecular biology at Cubist Pharmaceuticals in Lexington, Massachusetts. But pharmacologist Steven Projan, who directs antibacterial research at Wyeth-Ayerst Research in Pearl River, New York, cautions that long-term animal studies are needed: “It's usually the case that things that interact with DNA are toxic.”

Another new class of antibiotic blocks an enzyme called peptide deformylase (PDF) that is essential to bacteria but not to mammals. The killing tactic is simple: Most newly made bacterial proteins are tagged with a one-carbon unit called a formyl group, which is clipped off later by PDF to activate the protein. Higher organisms don't use this sort of protective wrapping on their proteins, so a compound that blocks PDF should in theory stop bacterial growth but leave human and animal cells alone.

Early results in animal models suggest that it does. John Clements and colleagues at British Biotech Pharmaceuticals Ltd. in Oxford have designed and chemically synthesized PDF inhibitors based on knowledge of the enzyme's three-dimensional structure. The inhibitors block the enzyme by clinging to a metal atom in the active site of the enzyme. One of the lead compounds, called BB-83698, effectively treated pneumonia in mice, overpowering even the penicillin-resistant microbes most dangerous to humans.

Another type of PDF blocker clears Staphylococcus aureus infections from the bloodstream of mice, Zhengyu Yuan and colleagues at Versicor Inc. in Fremont, California, reported at the meeting. The compounds, called urea hydroxamates, also fit into the active site of the enzyme, Yuan says.

Although PDF is a “good target,” compounds that block it could run into problems, cautions Malcolm Page, head of discovery biology at Basilea Pharmaceutica Ltd. in Basel, Switzerland. Bacteria might evolve resistance easily, and at least some strains can get by even with minimal PDF, he says.

Hurdles aside, the two classes of antibiotics are “exciting new possible therapeutic agents,” says microbiologist Abigail Salyers of the University of Illinois, Urbana-Champaign. With drug resistance on the rise, she adds, “we really need to have as many backups as possible.”

• *Interscience Conference on Antimicrobial Agents and Chemotherapy, 16-19 December 2001.

16. SPACE BIOMEDICINE

# An Rx for Astronauts

1. Andrew Lawler

The new director of the National Space Biomedical Research Institute hopes to strengthen a NASA experiment in improving the health of U.S. astronauts during and after long flights

BOSTONKeeping astronauts healthy is no easy task. Bone and muscle loss, crippling nausea, disorientation, and low blood pressure are just some of the threats they face from long-duration flights. While researchers struggle to understand and counter these problems, tight budgets, limited experiment time in space, and the field's shaky scientific reputation make their job even tougher. But for Jeffrey Sutton, a 43-year-old neuroscientist at Massachusetts General Hospital in Boston, the challenge is worth abandoning a successful career in academia and braving Texas's sweltering summers.

Next month Sutton takes over as the first onsite director of the fledgling National Space Biomedical Research Institute (NSBRI) in Houston. NSBRI is a consortium of U.S. universities and medical centers funded by NASA to carry out research on human space exploration. Created in 1997, it has grown to a $25.5-million-a-year operation, with a dozen academic partners and a portfolio of 90 research projects. Sutton is an outsider in a field dominated by a small and aging cadre of researchers. He hopes to use his eclectic background in medicine, brain research, and theoretical physics to help the institute produce a range of space-related drugs and devices and attract a new generation of top-notch investigators. The appointment of the Canadian-born Sutton is seen as a coming of age for a field hobbled by the perception of parochialism and a dearth of excellent research. “He's young, well respected, and enthusiastic—and he's not part of the space mafia,” says Laurence Young, an astronautics professor at the Massachusetts Institute of Technology (MIT) who is stepping down as founding director. Sutton says the new job will give him the chance to meld medical research and advanced technology in a setting more dynamic and collaborative than most academic laboratories. But his welcome has been less than hospitable: Within weeks of his appointment in November, NASA surprised him by paring$3.4 million from his budget. That news came amid budget-related delays in the construction of the international space station and a leadership vacuum at NASA, where both the biological and physical sciences office and the life sciences division at NASA headquarters remain without a permanent head.

Sutton says NASA will remain the institute's primary funder, although he hopes to attract significant support from small, nimble companies and a defense establishment eager to capitalize on new applications that could revolutionize intensive care units and field hospitals on Earth. And he's betting that the organization's streamlined management structure will make it “a poster child” for an economy-minded Bush Administration.

Sutton jokes that his academic training “is the reverse of the American dream—from riches to rags.” He began with a medical degree from the University of Toronto in 1982, then moonlighted in the emergency room while studying for a master's degree in neuroscience and a Ph.D. in theoretical physics. He says the doctorate gave him a deeper understanding of the connections between physics and neuroscience, which he pursued at Harvard Medical School. He also worked with a brain-mapping group at Harvard's Mass General before founding the neural systems group.

His first contact with the space field came in 1999 at an NSBRI workshop on smart medical systems. Institute leaders offered him the job of team leader, and, although he remained based in Boston, he later took over the advanced technology team as well. After an unsuccessful nationwide search following Young's decision to step down, the institute's board set its sights on Sutton. They invited him to dine with astronauts and took his two sons, ages 7 and 9, to a major league baseball game. The institute's collaborative culture, he says, was a far cry from the “malignant narcissism” that dominates MIT and Harvard.

The institute follows the National Institutes of Health model of peer review. But rather than exploring basic biomedical questions, the projects are linked to real-world problems such as bone loss, infection, and muscle atrophy, as well as an improved response to medical emergencies. For example, one team is testing bloodless surgery techniques using high-intensity focused ultrasound, while another is developing a sensor that can measure skin-cell tissue pH without breaking the skin. A group has recently been formed to examine the neurobiological and psychosocial factors of space flight, breaking a NASA taboo against probing the mental health of astronauts.

To support these and other projects, Sutton hopes to quadruple the institute's budget over time. “We need more money,” he says, “but not necessarily from NASA.” So far, however, Sutton says the institute's efforts to create an industry forum have been a flop. “It's not even 'Do Not Resuscitate.' [The patient] has yet to be awake.” There are also problems with the current allocation system, he says, which is based on “a socialist model” of equitable portions to all. The institute, he adds, is tainted by “a false perception of cronyism, of good old boys feeding off NASA's trough.” He also hopes to give team leaders greater autonomy to set their research agendas.

Sutton's job has been made more difficult by cuts in the space station budget that, at least for the time being, will limit the number of astronauts on board and the time available to conduct experiments. With only 10 to 20 hours of crew time a week, says Young, “the science will be disappointingly small.” And other institute advisers say they worry that the new director may become ensnared in NASA's tangled politics.

But Sutton says that the institute itself presents an interesting experiment. “There are no others I know that are run this way, with industry, government, and academia working together, and with proposals passing strict peer review,” he says. Win or lose, his attempts to reshape the institute and the field of space biomedicine will be reviewed carefully by his peers.