# News this Week

Science  15 Dec 2006:
Vol. 314, Issue 5806, pp. 1666
1. U.S. RESEARCH SPENDING

# Scientists Feel the Pain as 2007 Budget Outlook Grows Dark

1. Jeffrey Mervis*
1. With reporting by Eli Kintisch and Erik Stokstad.

The Republican Congress adjourned last week without passing a 2007 budget for most federal agencies, choosing instead to extend a temporary spending measure until 15 February. And this week, the incoming Democratic leadership announced plans to apply current spending levels for the entire fiscal year, which ends 30 September, so that it can make a fresh start on the 2008 budget. Those decisions will put the squeeze on many research agencies and the scientists funded by them.

“There are no good options available to us to complete the unfinished work of the Republican Congress,” declared Representative David Obey (D-WI) and Senator Robert Byrd (D-WV), incoming chairs of the appropriations committees in the House and Senate, in an 11 December statement. “After discussions with our colleagues, we have decided to dispose of the Republican budget leftovers by passing a yearlong joint resolution. We will do our best to make whatever limited adjustments are possible … to address the nation's most important policy concerns.”

The yearlong resolution, if adopted once the new Congress convenes next month, would limit agency spending to the lowest of what either the House or Senate has already approved or what the agency received for the 2006 fiscal year. The biggest scientific loser would be the Administration's proposed American Competitiveness Initiative (ACI), which calls for a 10-year doubling of research at the Department of Energy's (DOE's) Office of Science, the National Science Foundation (NSF), and the in-house National Institute of Standards and Technology labs.

But some agencies are already feeling the effects of the delayed passage of their 2007 budgets. DOE's Brookhaven National Laboratory in New York, for example, may have to cancel the next run of its Relativistic Heavy Ion Collider if the lab doesn't receive its budget by 1 February. That's because a delay will push the next 20-week session into the summer months, when the cost of electricity is prohibitive. Some scientists in the Sea Grant program funded by the National Oceanic and Atmospheric Administration (NOAA) could miss the boat, as delays in the scheduled 1 February awarding of some 50 grants could prevent them from obtaining ship time or hiring the next crop of graduate students. And investigators with funding from the National Institutes of Health have been told to expect only 80% of what NIH initially committed for the next year of their multiyear grant.

“It was unfortunate that Congress couldn't get its work done,” says John Marburger, the president's science adviser. “It's especially disappointing that it left without an ACI appropriation,” he adds, noting that spending panels in the House and Senate separately came close to matching the president's request. “At least they passed the tax package [see sidebar, p. 1666], which was the most expensive part of ACI, although we would like to see it made permanent.”

Federal research officials say their watch-word is caution as they await final word on their 2007 budgets. “We're being very conservative with pay lines and the size of awards,” says Norka Ruiz Bravo, head of NIH's external research program. The Administration requested no increase for NIH in 2007, and a last-minute bump-up seems unlikely despite its widespread support in Congress (see sidebar). Whatever happens, NIH Director Elias Zerhouni has three priorities: “Maintain our ability to fund new investigators, support the first competing renewal of first-time grantees, and preserve the capacity of outstanding PIs [principal investigators] who have no other support.” But he admits that there's no magic formula for achieving those goals within a steady-state budget. “The pain is real,” he says.

NSF Director Arden Bement says that “the results would be dire” if Congress sticks to a yearlong spending resolution. The administration had requested an 8% boost, and Congress seemed inclined to go along—the House approved the full request, and a Senate spending panel came close. But without an increase, he warned, mandatory pay raises for staff and the rising cost of materials for new facilities would require cuts in existing programs.

At some agencies, those cuts are already being made. The 2007 NOAA budget passed by the House is, at $3.4 billion, half a billion dollars smaller than its 2006 budget. The$380 million Office of Oceanic and Atmospheric Research, for example, which handles much of the agency's extramural grants, will likely need to delay the next round of Sea Grant awards. Office chief Richard Spinrad says the delay is especially hard on young investigators with few grants from other agencies.

That's also the case at DOE's Jefferson accelerator lab in Virginia, which is limping along on a budget that was cut by 10% in 2006. That puts a squeeze on planning for an upgrade to its main machine, including experiments at lower energies that are often the lifeblood of young academic scientists vying for tenure. Even if the cuts are eventually restored, “it's going to be hard to do all the work necessary for the short-term experiments and to prepare for the upgrade,” says nuclear physicist Ronald Gilman.

2. U.S. RESEARCH SPENDING

# Congress Extends Tax Credits for Industry

1. Eli Kintisch

On its way out the door, Congress gave the U.S. business community a parting gift for the holidays: $16 billion in tax credits for money it spends on research and development. Legislators extended the current credit for 2 years and broadened the number of eligible firms. First enacted in 1981, the R&D tax credits cover corporate investment in everything from drugs to automobile parts. Last year, U.S. companies claimed$5.2 billion in credits. But companies couldn't count on the tax break: It's been extended 11 times and last expired on 31 December 2005.

Businesses and, this year, the White House have long lobbied for a permanent credit. But lobbyists say they are grateful for the extension, which is retroactive to 2006. “At least we got out of it with the best result we could,” says Washington, D.C.-based business lobbyist David Peyton.

Under the current rules, companies can claim a credit if research spending rose over previous years as a ratio of revenue. The new bill simply provides a credit for any increase in R&D alone, a change that Monica McGuire of the National Association of Manufacturers in Washington, D.C., hopes will double or triple the number of companies able to claim a credit, which will “make the U.S. more competitive.”

The congressional move has its critics, however, including Citizens for Tax Justice in Washington, D.C. The nonprofit says the system is already too “open-ended” and “heavily abused” by corporations for expenditures unrelated to innovation.

3. U.S. RESEARCH SPENDING

# Congress Endorses Bigger NIH Budget, Director's Fund

1. Jeffrey Mervis

The National Institutes of Health (NIH) received a big pat on the back last week from the outgoing Republican Congress. In the waning hours of its final session, the 109th Congress approved legislation that authorizes higher budgets for NIH and spells out how the agency should conduct its business. Although the bill doesn't actually provide any new money, agency officials and the biomedical community hope that it will help them make the case for a bigger NIH budget with the new, Democrat-controlled Congress.

“We've been under a lot of scrutiny in the past few years, about how we operate and what we did with the recent doubling [of NIH's budget],” says NIH Director Elias Zerhouni. “So I see this as a reaffirmation of what we have been doing.”

The 3-year reauthorization calls for NIH to receive budget increases of 6% and 8% in 2007 and 2008, respectively. It creates a common fund for novel ideas and trans-NIH projects—a mechanism that is already up and running as part of Zerhouni's Roadmap Initiative—and calls for its share to grow to 5% of NIH's total funding as the overall budget rises. (NIH is staring at a possible flat budget in 2007 after a cut last year.) The bill, which President George W. Bush is expected to sign shortly, also sets in motion a review of NIH's current structure of 27 institutes and centers, with a report to Congress in 18 months.

Although federal agencies get their money from annual appropriations, authorization bills give legislators a chance to address pressing problems as well as to fine-tune an agency's programs. A big problem for NIH in recent years has been its bungled oversight of interactions between intramural scientists and managers and industry, which led to several egregious examples of financial conflicts of interest (Science, 11 February 2005, p. 824). Legislators have also been curious about how well NIH had spent a 5-year doubling of its budget that ended in 2003—especially whether its administrative structure was up to snuff.

The bill (H.R. 6164) was a priority for Representative Joe Barton (R-TX), outgoing chair of the House Energy and Commerce Committee, which held several contentious hearings on those topics. Passed overwhelmingly by the House in September, the bill contained a 5%-a-year boost for NIH and would have required the common fund to get half of any NIH increase. Voting last week, the Senate removed the mandatory 50-50 split and upped the annual increases, changes that Barton accepted reluctantly in return for setting a minimum size for the common fund, now roughly 1.3% of NIH's $28 billion budget. Biomedical lobbyists say they much prefer the Senate version that prevailed. The House bill would have restricted the ability of appropriators to target spending, notes Jon Retzlaff of the Federation of American Societies for Experimental Biology in Bethesda, Maryland. “If they wanted to add$100 million for some research program, they would need to give NIH $200 million,” he says. In an era of tight budgets, say Retzlaff and others, such a split would siphon off money needed to preserve existing programs and awards to individual investigators. Zerhouni acknowledges that the reauthorization isn't a substitute for a budget increase. But he says it would be “cynical” to dismiss it entirely. “I'd rather have a bill that says we need more dollars than no bill at all. It's really a big vote of confidence for us.” 4. PLANETARY SCIENCE # A Dry View of Enceladus Puts a Damper on Chances for Life There 1. Richard A. Kerr With the discovery last year of a great plume of water rising from the south pole of Saturn's icy moon Enceladus, astrobiologists had a new potential home for life in the solar system. Liquid water is the scarcest requirement for life, and the plume's striking resemblance to the Old Faithful geyser back on Earth seemed to imply subsurface pools. But an alternative explanation for the Enceladus plume, proposed on page 1764, would create the Old Faithful look without a drop of liquid water and therefore with no possibility of life. The concept of an Earth-like geyser on Enceladus emerged from early observations by the Cassini spacecraft orbiting Saturn, reported in the 10 March issue of Science (p. 1422). Each second, about a bathtub's worth of water in the form of water vapor and tiny ice particles soared hundreds of kilometers above the airless moon from a relatively “warm” (145 kelvin) spot on the surface. Cassini team members concluded in one paper that liquid water as little as 7 meters beneath the surface could be boiling as it encountered lower pressures. That would generate vapor and frozen droplets that jet out from crevices in the moon's icy crust. There was one snag, says Susan Kieffer, a geological fluid dynamicist at the University of Illinois, Urbana-Champaign, who has studied the dynamics of Old Faithful. On reading an accompanying Cassini paper, Kieffer and her colleagues learned that the spacecraft's mass spectrometer had detected considerable amounts of carbon dioxide, methane, and nitrogen in the plume. That was odd, they thought, because nothing like those amounts of methane and nitrogen could possibly dissolve in the water. Although water couldn't hold the gases, water ice could, by trapping individual gas molecules within the “cages” of ice's own crystal structure. The existence of such clathrates on Enceladus had been hypothesized 20 years ago. Kieffer and her colleagues reasoned that if clathrates lurked beneath a several-kilometer-deep crust of water ice, and tectonic activity created fractures in the crust, the pressure release would drive explosive decomposition of the clathrate. The required gases would gush out, along with ice particles that would sublimate enough water vapor to reproduce the observed plume composition. Their rough calculations support that scenario. “It's a noble and proper attempt to account for the gases,” says planetary meteorologist Andrew Ingersoll of the California Institute of Technology in Pasadena, a member of the Cassini team. But “it's not as simple as” uncorking some clathrates, he says. There are many details in the physics, such as how much water vapor ice particles could yield, that he needs to understand before taking back a potential habitat for life. 5. INTERNATIONAL AFFAIRS # Iranians Fume Over a Closed SESAME 1. Yudhijit Bhattacharjee A scientific project that hopes to be a calming influence in the Middle East has instead increased tensions between two important countries in the region. At issue is the failure of 35 Iranian scientists to obtain Egyptian visas for a recent meeting in Alexandria of researchers hoping to work on the Synchrotron Light for Experimental Science and Applications in the Middle East (SESAME) project. Eight countries are now members of a consortium creating a home for a synchrotron, donated by Germany, at a site 32 kilometers outside Amman, Jordan (Science, 26 November 2004, p. 1465). The machine, a first for the region, is intended to serve starting in 2010 as both a platform for research and a model for peaceful cooperation. Eight countries—Jordan, Bahrain, Cyprus, Egypt, Israel, Pakistan, Palestine, and Turkey—are already members, and the Iranian parliament is expected to vote sometime next year on a proposal to formally join a project in which its scientists have participated since 2001. But that vote could be influenced by what happened after the Iranians applied for visas to attend the 5-day Alexandria meeting, held the last week of November. The scientists say they never heard from the Egyptian embassy in Tehran after submitting their visa applications at least 6 weeks beforehand. “If this is not hostile treatment, I don't know what is,” says Reza Mansouri, a physicist at Sharif University in Tehran and one of two Iranian representatives on the SESAME council. Iranian contingents have attended four previous user meetings held elsewhere in the region, but Mansouri fears that the latest incident will bolster opposition in parliament to any collaboration. Egyptian authorities deny snubbing the delegation. The Iranian scientists simply did not apply early enough, says Egypt's science minister, Hany Helal. “It is exactly the same when an Egyptian submits a request for a visa to [go to] the U.S. or a European country,” says Helal. The council, which met in Jordan last week (Mansouri stayed home in protest), seems willing to give Egypt the benefit of the doubt. “It appears that the Iranians were given incorrect advice by the Egyptian embassy,” says Herman Winnick, a physicist at the Stanford Linear Accelerator Center in Palo Alto, California, who helped initiate the project a decade ago and remains an adviser. “It's extremely unfortunate.” Winnick says he hopes the incident will not prevent Iran from becoming a member country. 6. SCIENTIFIC MISCONDUCT # Online Sleuths Challenge Cell Paper 1. Hao Xin When scientists at National Chung Hsing University in Taichung, Taiwan, published a microbiology paper in the 20 October issue of Cell, local media hailed the event, noting that it was the first report in the prestigious journal by an all-Taiwan group. One newspaper quoted the university president as saying that the “findings will rewrite textbooks.” That local pride, however, was premature: After anonymous online sleuths raised questions about image manipulation in the paper, a university investigating committee has recommended that Ban-Yang Chang, the corresponding author, retract the paper. In an e-mail to Science, Yu-Chan Chao, dean of the College of Life Sciences at the university, calls the episode an “unfortunate case.” But Chao went on to say that Chang's team had provided “repeatable data suggesting that their overall conclusions were correct and reproducible.” The Cell paper, which questioned prevailing views of how transcription of a gene's DNA begins in bacteria, was challenged publicly on 16 November when an anonymous posting appeared on an electronic bulletin board run by Chinese students in the United States. The posting alleged that starting with figure 2 of the paper, “several dozen western lanes appeared to be copied and pasted.” The board has been abuzz with discussions about the study since then. Another poster claimed to have used “difference blending,” a feature of the image software Adobe Photoshop, to compare the upper parts of lanes in the high-resolution version of panel C of figure 2 of the Cell paper and concluded that they were almost identical. A subsequent reply on the board attributed to Chang denied any wrongdoing. And in an e-mail to Science last week, before the university investigation, Chang denied that images in the paper had been manipulated and stated that the “conclusion we made for the Cell paper is true on the basis of our data.” The paper dealt with the role of a transcription factor called sigma factor, a subunit of the RNA polymerase (RNAP) complex that transcribes DNA into messenger RNA. Sigma factor “melts” double-stranded DNA, separating the two strands to provide access for the polymerase, but it was thought to need the help of the core part of the RNA polymerase complex to bind to DNA. Chang's team, however, claimed to find that a truncated version of sigma factor could bind and open up DNA, without help from the core RNAP. A commentary in the same issue of Cell noted that the study adds “a twist to our current understanding of transcription initiation.” After Chang's online rebuttal, bulletin-board posters said they would contact Michael Rossner, managing editor of the Journal of Cell Biology and an expert on detecting image manipulation. Rossner confirmed to Science by e-mail that he was familiar with the case and “agree[s] with the students that some of the images are indeed questionable.” Cell also received word of the allegations and started an investigation, confirmed Emilie Marcus, the journal's executive editor. (As Science went to press, Cell had not published a retraction, and Chang had not conf irmed that he was retracting the paper.) Last Friday, Chung Hsing University convened a committee, which consisted of two university vice presidents, the dean of the College of Life Sciences, and two top scientists from outside the university, to investigate the alleged manipulation. They advised Chang to retract the paper, Chao wrote. “The university will take this as a serious lesson for ethics education at all the colleges in the future,” he added. There may be more lessons to come. Bulletin-board posters have challenged figures in another paper by Chang's team that was published online 16 October by the Journal of Biological Chemistry. 7. SEISMOLOGY # Do Early Tremors Give Sneak Preview of Quake's Power? 1. Alexander Hellemans* 1. Alexander Hellemans is a writer in Paris, France. Seismologists can give residents of earthquake zones a few seconds' warning of a coming quake—enough time to shut down nuclear reactors and slow high-speed trains—by analyzing the first waves the quake produces. But key information has been missing. “We know in a few seconds where an earthquake occurs, but we cannot predict the magnitude,” says Paul Rydelek of the National Research Institute for Earth Science and Disaster Prevention in Tsukuba, Japan. Now, Italian researchers say the same waves can reveal how strong the tremor will be, allowing a more appropriate disaster response. Some experts are skeptical, but Marie-Paule Bouin of the Institute for the Physics of the Globe in Paris finds the data presented by the Italian team “convincing enough” to be looked at seriously. The first earthquake signals to arrive at a seismic station are the primary or p-waves, which are compression waves like sound in air. P-waves travel fast, about 6 kilometers per second, but they do not carry the destructive force of the secondary or s-waves: shear waves that cause the ground to oscillate. S-waves travel at 3.5 kilometers per second and, depending on the distance to the epicenter, can arrive several seconds later. Early Earthquake Warning (EEW) systems work by spreading seismic detectors over earthquake-prone regions and using fast digital processing to give a few seconds' warning of a coming quake (Science, 24 December 2004, p. 2178). By combining the signals received at several stations, an EEW can estimate the position of the epicenter, but judging the magnitude of the quake is trickier. Seismologists can get a rough estimate from the frequency of the early p-waves. But Aldo Zollo and his colleagues at the University of Naples and the National Institute of Geophysics and Volcanology in Rome think the amplitude, or strength, of the p-wave can give a better indication of the tremor's destructive power. The Italian researchers analyzed records from seismic stations sited less than 50 kilometers from the epicenters of 207 earthquakes that occurred between 1976 and 1999 in the Mediterranean area. The magnitudes of the quakes ranged from 4 to 7.4. The team compared the peak amplitude of the first 2 seconds of the p-waves to the amplitude of the s-wave in their sample and found that both quantities correlate closely enough with the quake's magnitude to be useful in EEW systems. To use that information to gauge the magnitude of an impending quake, forecasters would need to know the distance to the epicenter. In a real-life situation, that information might not arrive in time, but Zollo thinks future EEWs will be able to supply it. “As the wavefront propagates in the network, you measure the amplitudes and compare the results of each station with the quantities measured at the other stations in the network,” he says. In this way, the network will quickly zero in on the location of the epicenter and the magnitude of the event, in time to trigger alarms at sites farther away seconds before the destructive s-waves arrive. Predicting earthquakes is a notoriously tricky business, and other researchers have expressed some skepticism over Zollo's claims of better warnings. Because Zollo and his team did not study quakes with a magnitude greater than 7.5, their technique may not apply to the most destructive events, says François-Henri Cornet of the Institute for the Physics of the Globe. “The conditions of the propagation of seismic wavefronts change at these magnitudes,” he says. Earthquakes also don't always develop in a tidy, symmetrical way. “The seismic wavefronts are often anisotropic, or are projected strongly in one direction, which can introduce errors,” admits Zollo. Errors aside, some researchers don't think it is possible to predict the magnitude of an earthquake, which depends on the total rupture length, by looking at seismic waves produced during its initial moments. “Once an earthquake begins, it will proceed essentially as a series of dominoes being knocked over. Sometimes the domino chain will stop, and at other times it will continue to go for a long distance,” says William Ellsworth of the U.S. Geological Survey in Menlo Park, California. Whether the start of the chain holds clues to its ultimate length “is still an open question,” he says. Zollo argues that the initial amplitude peak of the p-wave does carry such clues. “The probability that a fracture grows to a larger size scales with the initial energy available. The stopping mechanisms become less efficient for earthquakes with an initially high energy,” he says. Rydelek, however, remains skeptical. “I would like to see the physics that links these first seconds to the rupture propagation over the whole fracture,” he says. “You can have twists and turns in the fault, and stress variability, and these really determine how big the earthquake gets, not the initial slip.” 8. ASTRONOMY # France to Launch First Exoplanet Hunter 1. Alexander Hellemans* 1. Alexander Hellemans is a writer in Paris, France. PARIS—The 200 or so planets discovered to date around other stars are all big balls of gas similar to Jupiter or Saturn. Earth-bound telescopes aren't sensitive enough to detect small, rocky planets like Earth that could harbor life. But all that should change at the end of this month when COROT, a space observatory built by France, is lofted into orbit. COROT will survey large areas of the sky, monitoring thousands of stars at a time for tiny telltale dips in brightness that reveal a planet passing in front of its star. “COROT will tell us about rocky planets in the very inner orbits. [It] will tell us that they exist. We are really looking forward to seeing its data,” says William Borucki of NASA Ames Research Center at Moffett Field, California. COROT, to be placed in a polar orbit by a Soyuz launcher, cost$46 million to build and is equipped with a 30-centimeter telescope and four charge-coupled device (CCD) array detectors. Two of the arrays are optimized to detect the tiny brightness changes of a transiting planet. Whereas Earth-based telescopes can measure changes in a star's luminosity of about 1%, good enough for them to detect Jupiter-size planets, COROT's detectors will be sensitive to changes of 0.01%. “Because of the absence of [Earth's] turbulent atmosphere, we can obtain a much higher photometric precision,” says Pierre Barge of the Astrophysics Laboratory of Marseille and leader of the COROT exoplanet working group. When looking at very small stars, COROT will be able to pick out the dimming of starlight by an Earth-sized planet, Barge says. “Around stars like our sun, COROT will be able to detect planets twice the size of the Earth.”

COROT will start out focusing on the galactic center, which is rich in stars, and will switch to point in the opposite direction before the sun comes into the telescope's field of view after a year of observation. Researchers will monitor about 60,000 stars, Barge says, and they hope to discover a few hundred warm, Jupiter-like planets and between 5 and 50 rocky ones.

COROT's other two CCD arrays have a faster sampling rate and are designed to spot seismic oscillations in stars. Many stars, our sun included, experience vibrations, which reveal themselves as tiny fluctuations in the luminosity of the star. “We use similar observation techniques to the one for looking for planets,” says Annie Baglin of the Observatory of Paris at Meudon, COROT's principal investigator. Stellar oscillations, which can each last from a few seconds to several hours, are now an important tool in stellar research. “From the oscillation frequencies of a star, we can learn about its geometry, its mass, and its internal structure,” says Meudon's Eric Michel, head of the COROT seismology group.

Although other orbiting observatories have studied stellar vibrations, COROT hopes to get better results with its larger telescope and with a novel method using the telescope's CCD arrays to keep the telescope steady. When making observations, researchers ensure that there are several bright stars with precisely known positions always in the telescope's f ield of view. “These stars become the anchors on which we hook the satellite,” says Baglin.

COROT will set the scene for the next space observatory that will look for rocky planets: NASA's Kepler mission, due to be launched in November 2008. It will be equipped with a 1-meter telescope and will observe the same area of sky unblinkingly for up to 6 years so that it can detect longer-period rocky planets farther from their stars, where conditions for life are better. “We will look at 100,000 stars like the sun, so we expect to find dozens of Earths in the inhabitable zone,” says Borucki, Kepler's principal investigator.

9. HUMAN EVOLUTION

# There's More Than One Way to Have Your Milk and Drink It, Too

1. Ann Gibbons

The adage that milk does a body good may be true for American celebrities wearing milk mustaches in ad campaigns: Many Americans and northern Europeans descend from cattle herders and carry an ancient mutation that allows them to tolerate milk at any age. But milk gives cramps and diarrhea to roughly half the world's adults, especially in Asia and West Africa. That's why lactose tolerance has been held up as a classic example of human evolution, in which some people inherited the trait to digest milk, and some didn't.

Now, an international team reports a revealing twist on this evolutionary story. In this week's issue of Nature Genetics, researchers describe three new genetic variants that arose independently in groups of Africans; each variant allows carriers to drink milk and eat dairy products as adults. The study shows that lactose tolerance evolved more than once in response to culture, says team leader Sarah Tishkoff of the University of Maryland, College Park.

It's also an elegant example of how evolution can find several solutions to the same problem, especially in the face of strong selection, says molecular anthropologist Kenneth Weiss of Pennsylvania State University in State College. “There is not just one way to tolerate milk but several ways,” he says. “It's very nice work because it shows that evolution isn't just about picking one gene and driving it.”

The textbook tale of lactose tolerance runs this way: All humans digest mother's milk as infants. But for most of human history, weaned children didn't drink milk. So they shut down the enzyme lactase, which breaks lactose into sugars. With the domestication of cattle 9000 years ago, it became advantageous to digest milk, and lactose tolerance evolved in people who raised cattle.

In 2002, researchers identified a genetic mutation that regulates the expression of lactase and allows Finns and other northern Europeans to drink milk as adults. But researchers were surprised that the mutation appeared at lower frequency in southern Europe and the Middle East, and it was missing in most African pastoralists.

Tishkoff organized a team to collect blood samples from 470 Tanzanians, Kenyans, and Sudanese from 43 ethnic groups. Her team sequenced the DNA of 110 individuals who also were tested for milk tolerance.

They found three new mutations in the same stretch of DNA as the European variant. The mutations turned up in varying frequencies in the Maasai and other Nilo-Saharan populations in Tanzania and Kenya, in Afro-Asiatic-speaking Kenyans, and in the Beja from Sudan; some people had all three mutations. People with any of the variants had higher blood sugar levels after drinking milk, a sign that lactose was being digested.

The researchers also found that the most common variant arose as recently as 3000 to 7000 years ago and spread rapidly. “This is extremely significant because it shows the speed with which a genetic mutation can be selected,” says zooarchaeologist Diane Gifford-Gonzalez of the University of California, Santa Cruz. Indeed, the data suggest that humans who could digest milk had a huge reproductive advantage. “This is the strongest signature of recent positive selection yet observed,” says Tishkoff.

The new data may also help explain why people tolerate milk to varying degrees. The ability to drink milk is “not a qualitative trait that you have or you don't,” says Weiss. Tishkoff thinks there are yet more variants, and her team is seeking them.

10. REGULATORY POLICY

# EPA Draws Fire Over Air-Review Revisions

In a controversial move, the U.S. Environmental Protection Agency (EPA) has changed the way it reviews its health standards for six of the most widespread and dangerous air pollutants. Agency officials say the decision, announced last week, is designed to speed the notoriously slow process of revising these standards. But critics charge that the real intent is to give political appointees more control—an allegation that a powerful senator has vowed to investigate.

EPA's National Ambient Air Quality Standards (NAAQS) have enormous consequences, influencing the regulation of vehicles, industry, and agriculture in many ways. Under the Clean Air Act, the standards must be based on scientific evidence to protect human health and the environment, without regard to cost. The pollutants—including ozone, lead, and soot—must be reviewed every 5 years.

Many observers believe the new review process has its roots in a political contretemps from a year ago, when Administrator Stephen Johnson ignored recommendations from staff scientists and the Clean Air Scientific Advisory Committee (CASAC) that a soot standard be tightened (Science, 6 January, p. 27). “It was a PR fiasco for the Administration,” claims Frank O'Donnell of the nonprofit Clean Air Watch in Washington, D.C., who thinks the Administration's goal with this revision is to prevent agency scientists from ever again making politically unpalatable recommendations. Just a week before the embarrassing episode, he notes, Johnson's deputy had asked for a “top-to-bottom review” of how EPA reviews the air standards.

Everyone agrees that the process is slow and cumbersome. EPA often misses the 5-year deadline, is sued by environmentalists, and ends up releasing incomplete or inadequate analyses. According to the new plan, a massive science review will be replaced with a slimmed-down “integrated science assessment,” which could be finished and reviewed more quickly. In general, this is seen as a good move.

Other major changes are less welcome. High-level policymakers will now be involved early on to help identify “policy-relevant science issues,” such as which dose-response model to use for turning observational data into an air standard. The current chair of CASAC—Rogene Henderson of the Lovelace Respiratory Research Institute in Albuquerque, New Mexico—thinks the purpose is to let upper-level management guide the analyses in ways that would make the recommended standards acceptable to the EPA administrator. In an earlier interview, George Gray, EPA's chief scientist, who helped design the new process, denied that the intent was political. “This is about efficiency,” he said.

In another change, CASAC will no longer review early drafts of policy assessments; it will see them only after they're released for public comment as proposed rules—along with industry and other groups. “This is a huge step backward,” says Philip Johnson of NESCAUM, a nonprofit association of air-quality agencies in Boston. He sees the changes as marginalizing CASAC and making it easier for the administrator to ignore its advice. But Henderson is more sanguine. “This won't interfere with duties of CASAC to be an honest broker of the science,” she says.

U.S. Senator Barbara Boxer (D-CA), the new chair of the Senate Committee on Environment and Public Works, called the new air review process “a dangerous turn” and pledged to make it “a top priority for over-sight in the 110th Congress.” The changes will apply immediately to the review of the ozone standard, for which a proposed decision is due in March, and the lead review, which is just beginning.

11. ARMS CONTROL

# Little Progress at Bioweapons Talks

1. Martin Enserink

At least nobody slammed the door shut. That's the good news, participants say, after a 3-week international conference to review the international treaty banning biological weapons. The meeting ended in Geneva, Switzerland, on Friday with a low-key consensus statement: The participants basically agreed to keep talking. But outside observers say the meeting failed in its real ambition: to beef up the 34-year-old Biological and Toxin Weapons Convention (BTWC). A protocol to start verifying compliance, which the United States firmly rejected 5 years ago, wasn't even on the table. And conflicts about technology transfer hampered progress on other fronts.

The BTWC, a treaty that bans development, production, and stockpiling of biological weapons, has always been a work in progress. Just four pages long, it provides no mechanisms to monitor compliance or investigate countries suspected of cheating. At so-called Review Conferences, held every 5 years, member states have long discussed ways to strengthen the convention. The need to do so became painfully clear in the early 1990s, when defectors revealed a vast Soviet program to weaponize smallpox and anthrax.

But negotiations launched in 1995 to create a verification protocol for the BTWC collapsed in 2001, in part because the United States feared that allowing international experts to inspect biotech facilities might give away defense or industry secrets (Science, 20 July 2001, p. 414). In the resulting disarray, the Fifth Review Conference in 2001 failed to agree on a final declaration.

Since then, countries have searched for other ways to strengthen the convention. They held three intersessional meetings about issues such as disease surveillance and codes of conduct for scientists. And they have floated a number of new ideas for shoring up the convention at the Sixth Review Conference. By Friday, however, it had become clear that few plans to strengthen the treaty had made it to the finish line. One obstacle was an action plan, introduced by Iran and adopted by the countries of the Non-Aligned Movement to reinforce an article of the BTWC that promotes the transfer of technology for peaceful purposes.

Such stipulations give developing countries an incentive to participate, says Jonathan Tucker, a Fulbright Scholar at the German Institute for International and Security Affairs in Berlin. But developing countries overreached, says Finnish delegate Kari Kahiluoto, who spoke on behalf of the European Union, by demanding support for public health programs, vaccines, and drugs—issues that don't belong in an arms-control deal, he says. The United States also balked at the prospect that easing export controls on dual-use biotechnology equipment could increase biological weapons proliferation, adds Tucker. Iran and others in turn shot down a U.S.-backed plan to ensure that countries enshrine the treaty in national laws and regulations.

The intersessional meetings will continue until the next Review Conference in 2011, and the list of topics has been expanded slightly. There's a plan to recruit more countries to the convention. And members will finance a new three-person support team in Geneva. But these are “very modest” improvements, says Alan Pearson of the Center for Arms Control and Non-Proliferation in Washington, D.C. Indeed, says Tucker, “It shows how dysfunctional this process has become that we're excited about such small steps.” But in negotiations like these, Kahiluoto says, “you can't even take a modest outcome for granted.”

12. OPTOGENETICS

# Shining New Light on Neural Circuits

1. Greg Miller

Emerging methods that combine genetics and optics have neuroscientists glowing about the possibilities.

When researchers from Yale University reported last year that they'd used a laser to activate neurons in fruit flies and in turn control the insects' behavior, even Jay Leno thought it was cool. In a skit, the Tonight Show host pretended to use a remote-controlled fly to harass President George W. Bush during a speech. “I thought it was actually quite funny,” says Gero Miesenböck, the neuroscientist who led the study. A video clip of Leno's skit elicited chuckles when Miesenböck played it during a presentation at October's meeting of the Society for Neuroscience in Atlanta, Georgia.

But the neuroscientists who packed the crowded lecture hall hadn't come for laughs. Miesenböck's talk was part of a symposium on “optogenetics,” an emerging field that combines tools from optics and genetics to visualize and stimulate the nervous system. Several of the new methods, such as the one Miesenböck developed for the fly experiments, use genetic manipulations to confer light sensitivity on specific groups of neurons, making it possible to control their activity with pulses of light. Many neuroscientists say such stimulation methods represent powerful new tools for investigating neural circuits. “I think it's really exciting,” says Liqun Luo, a neurobiologist at Stanford University in Palo Alto, California, who attended the symposium. “It's at the cutting edge.”

Currently, several new photostimulation methods are in various stages of development, and scientists are just beginning to use them to address questions about brain function. But down the road—way down the road—some researchers envision exciting clinical applications. One idea is to replace the metal electrodes used for deep-brain stimulation in patients with Parkinson's disease and other disorders with fiber-optic probes that carry light deep inside the brain to boost the activity of only those neurons that need it.

## Lighting up

Using light to manipulate the nervous system is not a new idea. In the past 20 years, researchers have done many experiments with neurotransmitters bound to molecules that change shape in response to light. Such “caged” neurotransmitters are inactive, but a pulse of laser light sets them free to activate their usual receptors. Glutamate, the brain's chief excitatory neurotransmitter, has become a particularly popular tool in caging experiments. Glutamate uncaged with lasers can stimulate synapses with precise temporal and spatial control; a team from Princeton University reported last year in Nature Methods that they had done this at up to 20,000 different locations in an excised slice of brain tissue. There are drawbacks, however. Because almost all neurons respond to glutamate, it's virtually impossible to target only neurons of a particular type. And the precise spatial control requires a stationary target—a nonstarter for researchers who want to study behavior in intact animals.

Miesenböck's fly experiments circumvent these problems. Together with graduate student Susana Lima, Miesenböck inserted a rat gene that encodes an ion channel into flies. Fly neurons normally don't make this cell membrane portal, which opens in response to ATP, the energy-storage molecule involved in cell metabolism. Using standard genetic engineering tools, Lima and Miesenböck created several fly strains that expressed the ATP-gated channel only in specific classes of neurons. Then they injected caged ATP into the flies. When liberated by a flash of light, the ATP opened the channels in the modified neurons and allowed sodium and calcium ions to rush in, thereby prompting the neurons to fire a burst of electrical impulses. Because only neurons made to express the channel could respond to light, precise aim wasn't necessary; a fly-sized spotlight did the trick.

In one strain of fruit flies, Lima and Miesenböck put the ATP-gated channel in just two neurons out of the roughly 100,000 in the fly's nervous system, the so-called giant fiber neurons that control the fly's escape reflex. A brief flash of light made these insects jump and frantically flap their wings. In another strain, the researchers restricted the channel to neurons that make the neurotransmitter dopamine. Stimulating these neurons with light made the flies more active and increased the time they spent exploring their enclosure, Lima and Miesenböck reported in the 8 April 2005 issue of Cell; it was this study that inspired Leno's skit.

These fly findings are consistent with the idea, suggested by many earlier studies, that dopamine helps animals predict rewards and punishments, Miesenböck says. One possibility, he explains, is that activating dopaminergic neurons increases exploratory behavior because flies interpret the dopamine burst as a signal that something good—or bad—is nearby. His team is now working on ways to target the ATP-gated channel to different subsets of the fly's 150 or so dopaminergic neurons so that their roles in exploratory and other types of behaviors can be investigated.

## Ball and chain

Richard Kramer of the University of California (UC), Berkeley, has been investigating ways to make neurons sensitive to light by modifying other ion channels. In 2004, Kramer, neuroscientist Ehud Isacoff, and chemist Dirk Trauner, both also at UC Berkeley, described modified potassium channels that open and close when exposed to different wavelengths of light. Their approach makes use of an unusual feature of a molecule called azobenzene. In visible light, an azobenzene molecule is relatively straight and measures about 17 angstroms from end to end. When illuminated by ultraviolet light (UV), however, it folds in the middle, shortening the distance between the two ends to about 10 angstroms.

To take advantage of this shape change, Kramer and colleagues incorporated azobenzene into a molecular ball and chain that attaches to the extracellular side of a common variety of potassium channel. First, they tweaked the potassium channel gene to create a favorable binding site and expressed the altered channels in transgenic mice. Then they bathed slices of brain tissue from these mice in a solution containing the ball and chain, which has three components. The ball is a quaternary ammonium ion that can fit snugly into the channel's pore and prevent the flow of potassium ions. Next comes an azobenzene molecule and then a compound called maleimide that links the azobenzene to the potassium channel. When azobenzene is in its long state, the chain is just long enough to allow the ammonium ball to plug the pore. But when a pulse of UV light converts azobenzene to its shorter, bent configuration, the ammonium plug is pulled from the pore and potassium can flow freely into the neurons.

Opening potassium channels typically inhibits neural firing, so in the 2004 work, UV light acted something like an off switch on neurons equipped with the azobenzene-modified channels. Kramer and company recently created a light-controlled on switch for neurons by further tweaking the potassium channel gene so that the protein admits sodium ions as well. When these modified channels are lit up with UV light, sodium rushes into neurons and excites them, the researchers reported in the November 2006 issue of the Journal of Neurophysiology.

The UC Berkeley group has also added an azobenzene photoswitch to glutamate receptors, ubiquitous ion channels in neurons that normally open in response to glutamate.

They described the receptors in the January 2006 issue of Nature Chemical Biology. Kramer, Isacoff, and Trauner will be part of a newly announced center for studying the optical control of biological function. Funded by the National Institutes of Health and run jointly by UC Berkeley and Lawrence Berkeley National Laboratory, the center is part of NIH's nanomedicine initiative.

## Help from algae

Across San Francisco Bay, Karl Deisseroth and colleagues at Stanford have developed yet another optogenetics approach, based on a light-sensitive ion channel found in a unicellular green alga. Called channelrhodopsin-2 (ChR2), the channel opens in response to light, allowing positively charged ions to pass through its pore. The photosynthetic algae use ChR2 to orient to light. Expressing the gene for ChR2 in neurons makes them fire when exposed to light, Deisseroth and colleagues first reported in the September 2005 issue of Nature Neuroscience.

With this approach, there's no need for extra steps such as adding caged ATP or azobenzene to neurons. “It's a very simple system because all you have to do is express this one protein, and now you can control the activity of the neurons with light,” says Edward Callaway, a neuroscientist at the Salk Institute for Biological Studies in San Diego, California. And unlike the ATP-gated channels and the azobenzene photoswitch, the ChR2 system can trigger neural firing within just a few milliseconds of being hit by a laser beam. That makes it possible to deliver light pulses that drive the neurons in precisely controlled patterns that mimic the normal chatter of neural activity, explains Gary Westbrook, a neuroscientist at Oregon Health & Science University in Portland. “I think the biggest advantage of channel-rhodopsin is the ability to stimulate with such high time resolution,” he says.

Westbrook's lab intends to express ChR2 in newborn neurons in the mouse hippocampus to study how these cells communicate with mature neurons as they integrate themselves into preexisting neural circuits (Science, 17 February, p. 938). “We don't know anything about the output of that population of cells,” Westbrook says.

Other labs are also using the ChR2 system. At the recent neuroscience meeting, Guoping Feng of Duke University in Durham, North Carolina, presented preliminary work he's done in collaboration with Deisseroth and George Augustine at Duke. Feng and colleagues have created two strains of transgenic mice, one that expresses ChR2 in the output cells in a specific layer of the cerebral cortex and another that expresses the light-sensitive channel in mitral cells in the olfactory bulb. These efforts have convinced Feng that the method “works really well in vivo.” Ultimately, he hopes to use the ChR2 system to investigate neural circuits involved in addiction and compulsive behavior. “Many neurological diseases are diseases of specific subtypes of neurons,” he says. “This will give us a way to target specific neurons to understand their function in the circuitry of the brain.”

At the neuroscience meeting, Deisseroth presented preliminary work that further illustrates the potential. He used a virus to put ChR2 into neurons in a slice of mouse hippocampus, genetically tagged the same neurons with a fluorescent dye so that they were visible under a microscope, and used a fluorescent indicator of calcium flux to monitor their activity. The ability to simultaneously see, stimulate, and record the activity of neurons with light is a powerful combination for investigating the connectivity of neural circuits, he and others say.

## Clinical vision?

The new optogenetics techniques should provide more sophisticated options for exploring the neural underpinnings of behavior, Miesenböck says. Although neuroscientists have long used metal electrodes to manipulate neural activity, it's nearly impossible to use electrodes to stimulate a distributed population of neurons simultaneously, he explains. “The dopamine experiment in the fly would have been impossible with electrodes because you have about 150 cells arranged in different clusters,” Miesenböck says.

Not that there are no obstacles. The main one at present, several researchers say, is the ability to deliver the required genes to specific classes of neurons. “All these methods rely on the ability to direct gene expression to a particular cell type,” says Callaway. “I think 5 or 10 years ago, we all thought that was going to be really easy, but it hasn't proven so easy to do.” Another hurdle is getting light to deep-lying parts of the nervous system; so far, the techniques have only been used in slices of brain tissue and areas close to the surface of the brain in live animals.

This last obstacle may not be insurmountable, however. Deisseroth's lab has been experimenting with using flexible optical fibers to stimulate ChR2-bearing neurons deep in the brains of awake, behaving mice. Off-the-shelf fiber optics are sufficient for stimulation alone, Deisseroth says, but more elaborate experiments that combine stimulation with recording and imaging—such as the ones he described in brain slices—may also be possible in live animals before long. And at the neuroscience meeting, Stanford applied physicist Mark Schnitzer showed off a microendoscope small enough to fit on the head of a freely moving mouse. The thumbnail-sized device weighs less than 4 grams, and its fiber-optic probes can reach any structure in the mouse brain. So far, Schnitzer's group has been using the device for imaging cells labeled with fluorescent dyes, but he says there's no reason it couldn't also be used to stimulate light-sensitive neurons.

Far in the future, it's conceivable that fiber-optic light stimulation could replace deep brain stimulation via electrodes, a method currently under investigation for Parkinson's disease, depression, epilepsy, and other disorders. “An electrode stimulates all the cell types” that happen to be near its tip, Deisseroth says. “It's generally understood that that will contribute to side effects and reduce the efficacy.” A better solution, he says, would be to target the stimulation to certain classes of cells. But Deisseroth cautions that “a lot of things have to fall into place for this to happen,” not the least of which is resolving the serious safety concerns about gene therapy in humans.

Another potential clinical application is restoring sight in people with retinal degeneration. In the 6 April 2006 issue of Neuron, researchers led by a team at Wayne State University in Detroit, Michigan, reported encouraging results from an experiment in which they used a virus to deliver the ChR2 gene to retinal ganglion cells in mice whose retinas lack photoreceptor cells. Retinal ganglion cells are normally insensitive to light. But adding ChR2 made them respond to light and made the animals' visual cortices responsive to visual stimuli. (Kramer's team has been experimenting with ways to add a photoswitch to these cell's natural ion channels by chemical means alone rather than introducing foreign genes.)

There's no reason the future clinical applications of photostimulation methods would have to be limited to the nervous system, Kramer adds. He can imagine doctors one day using fiber-optic probes to examine the heart and other organs—using light to perturb a few specific cells that had been temporarily made light-sensitive by genetic or other means and recording a physiological response. Kramer is quick to add that any such clinical payoffs are a long way off: “It's so far out there who knows if it will ever happen,” he says. But when it comes to basic neuroscience research, he and others are confident that the new optogenetics methods have a bright future.

13. VITALY GINZBURG PROFILE

# After a Lifetime in Russian Science, Concern for the Future

1. Bryon MacWilliams*
1. Bryon MacWilliams is a writer in Moscow.

In his 90th year, Vitaly Ginzburg sees promise in Russian science but says, “I don't like very much what is happening now in our country”

MOSCOW—If anyone ever wanted proof that intellectual capacity is not limited by physical space, it can be found in the office of Vitaly L. Ginzburg, the Nobel laureate. The room is long and narrow—smaller than the wardrobe closet of a New Russian. It is so narrow, in fact, that plaster has been knocked out of a wall in two places by the desk chair, which cannot be pushed back far enough to sit down or get up comfortably. And Ginzburg, who celebrated his 90th birthday in October, is a tall man.

Creature comforts have always been an extravagance at the P. N. Lebedev Physical Institute of the Russian Academy of Sciences, where Ginzburg carried out much of his prizewinning theoretical studies of superconductivity. Formulas still are worked out for all to see on a wide green chalkboard that hangs in a central corridor.

These days, Ginzburg's office is unused. Yellow Post-it notes hang, dusty, from cabinet doors. Cracks in the windows are covered with packing tape. Debris from the ceiling is scattered over stacks of papers and books on the windowsill. A calendar says 2003—the year Ginzburg was awarded the Nobel Prize in physics with two others, Alexei A. Abrikosov and Anthony J. Leggett, for their contributions concerning two phenomena in quantum physics: superconductivity and superfluidity. In the 1950s, Ginzburg helped develop a theory on the behavior of superconductors—metals, alloys, ceramic compounds—in a magnetic field, laying the groundwork for further studies on so-called Type 2 superconductors, which pass electricity without resistance at higher, more practical temperatures. They are used, for example, in magnetic resonance imagining and particle acceleration. Not long after receiving the prize, Ginzburg was diagnosed with Waldenstrom macroglobulinemia, an extremely rare cancer of the blood that is treatable but incurable. He lived and worked for nearly 2 years in a hospital bed.

Late last summer, he was told that he had recovered enough to go home. “If my secretary tries to say that I'm doing well, don't believe her,” says Ginzburg, a good-humored man who, nevertheless, characterizes himself as “rather grave.”

Ginzburg sleeps and works in his airy study in a spacious Moscow apartment that is teeming with houseplants. The time he once spent undergoing treatment he now spends writing in light-blue flannel pajamas at a large wooden desk, above which hang two photographs: one of his wife, Nina, and the other of the two of them out on the town. He calls the office regularly. “He doesn't want to lose contact with the outside world,” says his secretary, Svetlana Volkova, who types the essays and letters that he writes, longhand, at all hours. The words are often scrawled in pencil in large letters, because he has yet to learn how to use a computer. He delights in the freedom enjoyed by theoretical physicists; he says they “possess a singular possibility to engage in a very wide spectrum of problems, since it is easy to move from one to the other on paper.”

Ginzburg is concerned with the worsening state of democracy in Russia, the creeping influence of religion in education, and the effects of what he calls “pseudosciences,” such as astrology. He is also concerned with euthanasia; he thinks the terminally ill should be allowed to die if they choose. He tries to keep up with research in physics, particularly superconductivity at warmer temperatures. “I also think a lot about my own fate,” he says. “I am grateful that they succeeded in giving me the prize before I died.”

Ginzburg focuses much of his energy commenting on the future of the Russian Academy of Sciences, the 282-year-old institution that, in exchange for government pledges to spend more money on salaries and laboratory equipment, recently ceded much of its autonomy to the state (Science, 10 November, p. 917). He may be the most prominent of a group of critics who claim that the Kremlin has been empowered to sell off the academy's assets—an “idiotic” plan, he thinks. “Undoubtedly, science in Russia has fallen behind. Essentially, some 20 years have been lost,” he says. “We cannot catch up to America, or even England. But, overall, it is possible to do good work here. A large number of highly qualified people remain.” The government should increase financing for the sciences, he says, but without favoring applied over fundamental research, or converting the institution into what is effectively a governmental department.

Although Ginzburg has been immobilized by illness, his assistants are keen to point out that his moral barometer is robust. “Please understand that I am a democrat at heart, and, of course, I don't very much like what is happening now in our country. … But I am not a political activist. I don't say all that I feel, as they would likely jail me,” he says, laughing. Still, he cannot be said to be biting his tongue.

He characterizes as a “return to the time of Stalin” the arrests since the late 1990s of scientists by the Federal Security Service. The charges, which Ginzburg and many other scientists consider to be flimsy, are that they sold state secrets. He rails against attacks on atheists, such as himself, by those who wish to bring church teachings into public schools and universities. He also denounces major newspapers, such as Izvestia, for publishing horoscopes, which he calls “pure hokum.”

Often he is asked what he has done with the roughly $350,000 in Nobel Prize money, an enormous sum in a country where experienced researchers are being promised 30,000 rubles ($1150) a month by 2008. He says that he has put the money away for the college educations of his two great-grandchildren, a twin boy and girl living in Princeton, New Jersey.

He sold his country house to help pay for medical treatment and likens his fate to that of two great Soviet physicists, Igor Y. Tamm and Lev D. Landau, both Nobel laureates with whom he worked. (Like Tamm, Ginzburg was recruited to help design the first Soviet nuclear bombs, but by a stroke of luck, he says in his Nobel autobiography, his low security rating kept him in Moscow, away from the Arzamas-16 military site.) Although he is proud to have followed in the footsteps of Tamm and Landau as a physicist, he says he is reluctant to be following “their path [to the grave].” He recounts their deaths in an essay on the Web site of a magazine for which he is editor, Uspekhi Fiziki, or Advances in Physics, which has been in existence since 1918.

Tamm, who suffered from amyotrophic lateral sclerosis, or Lou Gehrig's disease, used to say that he was attached to a respirator like “a bug on a pin” in a specimen case. Landau died over the course of 6 years after sustaining painful injuries in a car accident. Ginzburg, saying he has a low tolerance for pain, recently laid bare his wishes in an essay titled, “On the Right to Die.” “From the very beginning of my illness, I have dreamed about death, but, of course, a painless death,” he writes.

He published the piece online in a relatively obscure publication, he says, to avoid being accused of encouraging euthanasia, a crime in Russia. “I have done all that I can. Within several months at the end of successful treatment, I most likely will have written, in my [90] years, a mere handful of articles and letters. It is absurd to suffer such long months for that. It brings me to recall the joke that goes, ‘Why do you exercise?’ The answer: ‘To die healthy!’”

Civil society, he says, is not sufficiently developed in Russia to enact a right-to-die law anytime soon. So he continues to write the essays and letters for which he has concluded that life is not worth living.

Increasingly, he has been publishing interviews and essays in the magazine Zdravy Smysl, or Common Sense—something that he says is missing from public discourse in his country. “What else can I do?” he says. “For now, living is in the cards.”

14. NUCLEAR PHYSICS

# Japan Gets Head Start in Race to Build Exotic Isotope Accelerators

1. Dennis Normille,

A new facility begins to explore the structure of the nucleus as Europe awaits two machines and the United States revises its plans

WAKO, JAPAN, AND ROSEMONT, ILLINOIS—Sometime this month, a warning siren will clear personnel out of the bowels of a massive concrete building in Wako, a city just east of Tokyo. Then, the world's most powerful cyclotron will propel a stream of uranium ions at a carbon target. The resulting smashup will produce radioactive nuclei that have never existed outside a supernova. Such fleeting exotic bits of matter should help unify a fragmented theory of the nucleus, reveal the origins of the heavier elements, and provide clues to why the universe contains so much more matter than antimatter.

Data from the $380 million Radioactive Isotope Beam Factory (RIBF) at the Institute of Physical and Chemical Research (RIKEN) in Wako “will allow us to form a new framework for nuclear physics,” says Hiroyoshi Sakurai, chief nuclear physicist at RIKEN's Nishina Center for Accelerator-Based Science, which built and will operate the machine. Richard Casten, a nuclear physicist at Yale University, agrees that knowledge sifted from the atomic shards “will be transformational in our understanding of nuclei.” But Japanese physicists aren't the only ones staking a claim to this fertile turf. RIBF is the first in a new generation of exotic isotope accelerators. Researchers in Germany and France hope to have machines ready to power up in 2010 and 2011, respectively. Meanwhile, a U.S. National Research Council (NRC) report released last week makes the case for building the most powerful machine of all. U.S. researchers hope the report will jump-start a project, once known as the Rare Isotope Accelerator (RIA), that stalled last year after the U.S. Department of Energy (DOE) ordered researchers to cut in half the projected$1 billion cost. “This report helps get the project unstuck by more clearly defining the science that can be done with it and the international situation,” says Michael Turner, a cosmologist at the University of Chicago and chief scientist at DOE's Argonne National Laboratory in Illinois, one of two institutions vying for the machine.

Accounting for more than 99.9% of an atom's mass and less than a billionth of its volume, the nucleus is a knot of protons and neutrons. Nature provides 260 stable nuclei, and researchers have glimpsed 10 times that number of unstable ones. But machines that produce even more would provide new insights into the structure of the nucleus.

For example, since the 1940s, physicists have known that nuclei with certain “magic” numbers of protons or neutrons appear to be more stable than might otherwise be expected. However, recent findings suggest that the known magic numbers—2, 8, 20, 28, 50, 82, and 126—may not apply to nuclei with an extreme excess or deficiency of neutrons, says Takaharu Otsuka, a theoretical physicist at the University of Tokyo. An exotic isotope accelerator could search for new magic numbers for highly unstable nuclei and help physicists develop a more comprehensive theory of the nucleus.

Experiments at RIBF will also allow researchers to “take on the challenge” of elucidating stellar processes, says Yasushige Yano, head of the Nishina Center. Scientists believe that half elements heavier than iron are created somewhere within supernovae by a phenomenon known as the R-process, in which nuclei become bloated with neutrons. The resulting neutron-rich nuclei then decay into the familiar stable elements. But physicists don't know precisely how, or even where, the R-process takes place. Studying fleeting neutron-laden nuclei in the lab should help remedy that situation, says Otsuka.

An exotic isotope accelerator might even help explain why the universe is rich in matter and essentially devoid of antimatter. Physicists believe that the imbalance emerged in the infant universe thanks in part to a slight asymmetry between matter and antimatter known as charge-parity (CP) violation, which has been observed only in two types of exotic particles called mesons. According to the standard model of particle physics, such asymmetry could be reflected in the properties of certain exotic nuclei, such as the distribution of electric charge within them. So those nuclei might reveal other sources of CP violation to probe one of the larger mysteries in the cosmos.

To pursue such goals, RIBF links an existing linear accelerator, or linac, and cyclotron with two new conventional cyclotrons and a superconducting ring cyclotron that together will accelerate even the heaviest nuclei up to 70% of light speed. The heavy nuclei will blast through a target of lighter ones and be ripped apart, like a car crashing into a steel post—a process called in-flight fragmentation. The exotic nuclei will be sorted into secondary beams and analyzed or smashed into still other nuclei.

But some of the science may have to wait for more funding. Although the beamline is ready, RIKEN lacks money for instrumentation and experiments. Some projects will start next year, but more complete instrumentation won't be in place until 2008, says Sakurai.

Still, that timetable gives RIKEN a big head start on the competition. Researchers at France's heavy-ion lab, GANIL in Caen, are working on SPIRAL2, a linac that will also produce exotic isotopes by in-flight fragmentation. SPIRAL2 will also smash light nuclei into heavy ones in a solid target to chip the target nuclei apart—a technique known as isotope separation online (ISOL). Meanwhile, researchers at Germany's GSI heavy-ion research center in Darmstadt await a green light to build the sprawling international Facility for Antiproton and Ion Research (FAIR), a synchrotron lab that will produce exotic isotopes, among other things. FAIR will create the nuclei by in-flight fragmentation and will accelerate them to far higher energies. GSI officials are hammering out an agreement with international partners, and construction could start next year.

Researchers in the United States hope that the NRC report will help them get back in the game. In 1999, nuclear physicists proposed using a high-energy, high-throughput linac to create RIA, a dream machine that would have excelled in every technique. In 2003, RIA tied for third on a list of 28 projects DOE hoped to complete within 20 years, and researchers anticipated construction starting as early as 2008. Argonne and Michigan State University in East Lansing were vying to host the machine.

But in February, DOE put the pricey project on hold and asked for something cheaper (Science, 24 February, p. 1082). DOE and the National Science Foundation (NSF) had already requested an NRC review of the science that RIA could do, and the Argonne and Michigan State teams suggested building a shorter linac with half the energy (but twice the beam current) and eliminating experimental stations. Last week, the review committee presented its analysis of the more modest proposal to members of NSF and DOE's Nuclear Science Advisory Committee (NSAC) at a meeting outside Chicago.

Even the smaller-scale machine would be worth building, the committee concluded. “There is a persuasive case for the science that can be done with this machine,” says committee co-chair John Ahearne, a physicist with the scientific society Sigma Xi in Research Triangle Park, North Carolina. That conclusion takes into account the foreseeable competitors, says co-chair Stuart Freedman, an experimental physicist at the University of California, Berkeley, who noted that “without a facility like this, this part of the [U.S. nuclear physics] community likely would not survive.”

The report cheered rare-isotope researchers. “It's very positive, very encouraging,” says Konrad Gelbke, director of the NSF-funded National Superconducting Cyclotron Laboratory at Michigan State. Donald Geesaman, a physicist at Argonne, says the report provides “validation of the importance of the science from a broader community” than just exotic-isotope researchers. Researchers now hope construction can begin in 2011 for a start-up in 2016.

Physicists still have a long way to go to transform their idea into a machine, however. First up is a design for the vaguely defined facility. Unlike RIA, the new machine won't do it all. Argonne researchers favor the ISOL approach, whereas Michigan State physicists favor in-flight fragmentation. Both groups would also pursue a novel scheme called reacceleration, catching isotopes in a tank of gas and then feeding them into a second accelerator. This spring, an NSAC subcommittee will weigh in on the matter.

Then there's the question of finding \$500 million to pay for the machine. Last year, DOE submitted to Congress a 5-year plan “that involves growth in the bottom line of the Office of Science, and this [facility] is part of the plan,” says Dennis Kovar, director of the DOE nuclear physics program. Whether the new Congress will go along, however, remains to be seen.