# News this Week

Science  27 Mar 2009:
Vol. 324, Issue 5923, pp. 20
1. INFECTIOUS DISEASE

# Hitting Early, Epidemic Meningitis Ravages Nigeria and Niger

1. Leslie Roberts

Nigeria and Niger are reeling from one of the worst meningococcal meningitis epidemics in years. Already, the epidemic has sickened at least 25,000 people, more than 17,000 in Nigeria alone, and killed 1500. World Health Organization (WHO) experts caution that those numbers may be underestimates and warn that the worst is yet to come. F. Marc LaForce of the Meningitis Vaccine Project (MVP), a nonprofit effort to develop an affordable vaccine to prevent such epidemics, worries that “this may be a repeat of 1996–97,” when the largest epidemic ever to hit Nigeria caused more than 100,000 cases and 11,000 deaths.

WHO, Médecins Sans Frontières (MSF), and others have rushed in teams to help state and local health officials deal with the outbreak. Several million doses of the scarce and outmoded emergency vaccine, which has limited effectiveness, have been released from the global stockpile and have begun arriving in both countries. Antibiotics have been sent as well to supplement country supplies. But meningitis experts fear these efforts may be too little, too late to curb the epidemic, which started unusually early this season, now in its 14th week.

The grim task now is triage. There is simply not enough of the existing, 1960s-era vaccine to protect everybody at risk—50 million in Nigeria alone. That leaves the International Coordinating Group (ICG) on Vaccine Provision for Epidemic Meningitis Control, a collaborative effort of WHO, MSF, UNICEF, and the International Federation of Red Cross and Red Crescent Societies, with the unenviable task of deciding which countries and states get how much.

Caused by the bacterium Neisseria meningitidis, meningitis is an infection of the thin membranes that line the brain and spinal cord. It is a frequent scourge of the countries of the African meningitis belt, which stretches from Ethiopia to Senegal. Almost every year, waves of meningococcal meningitis arrive with the harmattan, the hot, dry wind that signals the start of the dry season in December or January, and then dissipate with the first rains, usually in May. Left untreated, meningitis kills roughly half of its victims; even with prompt treatment, up to 10% die and up to 25% are left with deafness or other disabilities.

Although epidemic meningitis comes like clockwork to Africa—for reasons that remain largely a mystery—no one can predict exactly where it will hit or how severe the outbreak will be. Nigeria and Niger have been largely spared in recent years—the disease tends to “jump around,” says LaForce. Every 10 years or so, a perfect storm of environmental and population conditions combine to spawn massive outbreaks across the entire belt, like the one in 1996–97 that killed more than 25,000 in 10 countries and sickened 250,000.

Because of this unpredictable epidemiology and the shortage and limited efficacy of the existing polysaccharide vaccine—immunity lasts just 3 years—WHO recommends that it be used in mass campaigns to control epidemics, not to prevent them. ICG releases the vaccine, effective against the main epidemic strain, serogroup A, only when a country can demonstrate that an epidemic has begun and the strain has been confirmed by lab analysis—a tall order in some remote areas. (This year, as usual, the predominant strain is serogroup A, but some W135 is circulating.)

WHO estimates that if a country can launch a mass vaccination campaign within 3 to 4 weeks of the epidemic's onset, roughly 70% of cases can be prevented. But the application request can be onerous, concedes epidemiologist William Perea, who coordinates WHO's epidemic readiness and interventions in Geneva, and often the vaccine arrives too late to do much good. In Nigeria, the first batch of 1.5 million doses of vaccine arrived in early March, in week 8 of the season; several million more doses are on the way. By week 5, six local government areas had already passed the epidemic threshold, and that number skyrocketed to 28 in week 8 and has kept climbing. Says Perea, “It is too soon to say whether it is having an effect on the epidemic curve,” which usually peaks 14 or 15 weeks into the season. Niger was better prepared this year, as it had 2 million doses of vaccine prepositioned and also applied earlier to the ICG.

Similarly, antibiotics can save lives, and overall supplies seem sufficient in both countries. But “they are not close enough to the patient,” says Stéphane Hugonnet, a WHO epidemiologist working with the hardest hit states in northern Nigeria. “The end result is either the drug is given quite late or another drug is given. Overall, case management is quite poor.”

Right now the biggest struggle is to get the vaccine where it can do the most good, say Perea and Hugonnet: to densely populated areas where the epidemic is still on the rise or is expected to hit hard. If the epidemic is already waning, “it's a waste of resources,” says Perea. “Unfortunately, countries don't always follow our epidemiologic recommendations.” Nigeria, for instance, has been distributing the vaccine evenly among all states, “even if it is not needed.” It's a tough call, he says. “Can you imagine being a minister of health of one of the states trying to explain that the curve is going down and they don't need vaccination?”

The rising toll is especially frustrating to LaForce of MVP, a partnership of the nonprofit PATH and WHO, because their inexpensive long-lasting conjugate vaccine designed to prevent such epidemics is almost ready (Science, 27 June 2008, p. 1710). Plans are being readied to vaccinate 5 million people, roughly half the vulnerable population, in Burkina Faso later this year; by then sufficient vaccine should be ready for a phased 6-year roll out across the rest of the meningitis belt. Citing the financial crisis, last year the GAVI Alliance, which was expected to fund the entire $370 million introduction package, provided just$29 million for 2009–10, as well as $55 million for the emergency stockpile. GAVI's decision was “very surprising” and “very, very frustrating,” says Perea. “It is not clear what will happen in 2 years.” Meanwhile, Kader Konde, who directs WHO's Multi-Disease Surveillance Center in Burkina Faso, worries that there will not be enough of the emergency vaccine to get through this season. By week 11, ICG's emergency stockpile was down to 10 million doses. (Manufacturers held another 6 million.) Perea thinks they will squeak by. But if the stockpile drops too low and the epidemic doesn't wane, he says, “we are ready to consider the use of fractional doses. We are developing contingency plans.” 2. EPIDEMIOLOGY # Children's Study Exhibits Healthy Appetite 1. Jocelyn Kaiser Perhaps the most ambitious long-term health study ever planned by the National Institutes of Health (NIH) has been hit by a NASA-style price shock: Once estimated at$3 billion over 25 years, the actual cost could be twice that much. The problem became public last week at a Capitol Hill hearing on the NIH budget. Acting NIH Director Raynard Kington said he has launched a high-level review of the plan to track the health of 100,000 children from before birth to age 21 and that the study will likely be scaled back.

The National Children's Study (NCS) grew out of a 2000 congressional directive to NIH to determine how environmental influences, from chemical contaminants to video games, shape the development of children and affect diseases such as autism and obesity. Researchers plan to recruit a diverse group of pregnant mothers at 105 sites around the United States by knocking on randomly selected doors (Science, 10 December 2004, p. 1883). Congress provided $192 million in funding this year to set up the sites and launch a pilot study. Kington says he became concerned in early January, after Duane Alexander, director of the National Institute of Child Health and Human Development, which runs the NCS, told Kington's office of his staff's latest cost projections. They ranged from a low of$3.4 billion—well over a previous $2.7 billion price tag—to a high of$6 billion, depending on how many of the 28 hypotheses explored in the pilot phase are retained in the full study. Kington says he realized that “there was a fundamental problem in estimating the true costs.”

Kington says he has now added “greatly heightened oversight.” That includes asking Claude Lenfant, who retired as director of the National Heart, Lung, and Blood Institute 6 years ago, to return to NIH as his adviser on the study. “Obviously, [Lenfant] has incredible experience” overseeing large studies such as the Framingham Heart Study and the Women's Health Initiative, Kington notes. NIH will also take a longer pause than originally planned after the 1-year pilot, which began in January at two of seven sites, to revise the protocol and reassess the costs. The final protocol will be sent for review to a National Research Council panel that reviewed the study plan last year and, as it happens, urged a longer delay (Science, 30 May 2008, p. 1147).

When trimming begins, Kington says he hopes the 100,000 sample size will be “the last thing” considered for cuts. But the size, number of hypotheses, and the protocols are all on the table. Pediatrician Philip Landrigan of Mount Sinai Medical Center in New York City, who helped conceive the NCS, hopes not to lose components such as in-home detailed assessments of each child's development, which are expensive. “We're just waiting to see how this works out,” says Landrigan, whose team has knocked on more than 1000 doors in Queens and found that many women seem interested.

The budget problems come as no surprise to former NIH Director Elias Zerhouni, who wanted to zero out funding for the NCS. Zerhouni says he had “severe reservations” about the potential cost and felt NIH should complete the pilot before any decisions were made about proceeding with the full study. Instead, “Congress interfered” by providing the money to move ahead anyway. “It was political management,” Zerhouni says, and “I don't think people should be shocked” at the result.

3. NEUROSCIENCE

# Sleeping to Reset Overstimulated Synapses

1. Greg Miller

The purpose of sleep is one of the toughest puzzles in biology. Some scientists think animals slumber primarily to save energy. Others have proposed that sleep has special relevance for learning and memory. A newer hypothesis borrows from both ideas, suggesting that sleep dials down synapses that have been cranked up by a day's worth of neural activity. Because stronger synapses use more energy and take up more space, the thinking goes, this synaptic cooldown helps conserve both energy and precious real estate in the brain. It also ensures that synapses don't max out and lose the ability to grow stronger if they're called upon to encode some new experience into memory the next day.

In this week's issue, two studies with fruit flies provide what some researchers say is the most compelling evidence to date for this provocative hypothesis. One finds that levels of several synaptic proteins increase during wakefulness and decline during sleep; the other finds a similar rise and fall in synapse number. “Together, these findings very clearly demonstrate that one major function of sleep is to reduce, on a structural level, synaptic connectivity in the brain,” says Jan Born, a neuroscientist who studies sleep at the University of Lübeck in Germany and was not involved with either study.

The so-called synaptic homeostasis hypothesis was first proposed about 5 years ago by neuroscientists Giulio Tononi and Chiara Cirelli at the University of Wisconsin, Madison. The idea had intuitive appeal and elegant simplicity but sparse experimental evidence. Since then, support has come from studies with rodents and people—and now, flies.

On page 109, Cirelli, Tononi, and postdoc Giorgio Gilestro report that depriving flies of sleep, either by periodically shaking the vials they call home or by forcing individual male flies to cohabitate with an unwelcome stranger (a male from another fly strain), resulted in higher levels of several synaptic proteins throughout the brain. Levels of these proteins, which included components of the transmitting and receiving sides of the synapse as well as proteins involved in neurotransmitter release, declined after flies had a chance to sleep. This pattern held up even when flies slept at odd hours, confirming that the proteins fluctuate with the sleep-wake cycle, not the time of day.

The second paper, on page 105, describes changes in synapse number during sleep. But the experiments weren't conceived as a direct test of the synaptic homeostasis hypothesis, says senior author Paul Shaw of Washington University in St. Louis, Missouri. Instead, the goal was to investigate how daytime activities influence subsequent sleep. Shaw's lab had previously found that flies sleep longer after social stimulation—either a fruit fly party in a vial or “courtship conditioning,” in which a male fly learns the futility of trying to mate with another male doused with female pheromones (Science, 22 September 2006, p. 1775).

The main goal of the new study, led by Shaw's graduate student Jeffrey Donlea, was to investigate how these daytime experiences affect the sleep of mutant flies. The researchers found that disrupting any one of three genes, including period, an integral component of the circadian clock, prevented flies from sleeping longer after a socially stimulating day. Restoring the genes in just 16 so-called ventral lateral neurons—out of some 200,000 neurons in the fly brain—was enough to restore increased sleep after social enrichment.

These findings provide an intriguing link between two major regulators of sleep, Cirelli says. The circadian clock tells animals when to sleep, she explains, but the duration of sleep depends on how long they've been awake and what they've done during that time. The new findings suggest that some of the same cells and genes involved in regulating the circadian clock may also be involved in sensing sleep need.

In the same paper, Donlea and colleagues also report findings that seem to support the synaptic homeostasis hypothesis: They found that the same social experiences that increase the need for sleep also increase the number of synapses between lateral ventral neurons and their partners in the brainstem. After sleep, synapse numbers had declined.

Together, the two papers provide compelling evidence for synaptic downscaling during sleep, says Robert Stickgold, a neuroscientist at Harvard University who was initially skeptical of Tononi and Cirelli's hypothesis. Even so, Stickgold thinks it's unlikely that downscaling happens only during sleep or that synaptic strengthening is limited to waking hours. Human and rodent studies have suggested, for example, that sleep may be important for consolidating newly formed memories (Science, 9 March 2007, p. 1360), a process that's widely assumed to depend on strengthening synapses.

And in a 12 February Neuron paper, neuroscientist Marcos Frank and colleagues at the University of Pennsylvania reported that synaptic communication between neurons in the visual cortex of cats can grow stronger during sleep. Such findings “raise the question of whether downscaling is all that sleep can do to synapses,” Frank says.

The apparently contradictory findings may just mean that the sleeping brain is multitasking, says Born. He suggests that an overall decrease in synaptic strength could help conserve space and energy in the brain, while at the same time synapses in specific neural circuits could be strengthened to reinforce newly encoded memories.

4. ASTRONOMY

1. Dennis Normile

TAKAHAGI, JAPAN—Two giant radio antennas on a hill above this small town may be an unlikely symbol of civic pride. But they are a reminder that the hardscrabble rural area 140 kilometers north of Tokyo was once at the telecommunications vanguard. The dishes are all that remains of Japan's first satellite receiving station. It went online 23 November 1963, just in time to carry live news reports of John F. Kennedy's assassination the previous day. When the telecom company shifted to optical fiber cables in 2007 and shuttered the station, local people sought a way to preserve their modest connection with history. As a result, the dishes are being reborn as radio telescopes for nearby Ibaraki University, to link into the formidable very long baseline interferometry (VLBI) array run by the National Astronomical Observatory of Japan (NAOJ) and as tools for stand-alone observations.

The antennas here are not the first telecom dishes to get a second, scientific lease on life, nor will they be the last. The next hand-me-down antenna due to come online is in Peru, where the Instituto Geofisico del Peru (IGP) in Lima is converting a 32-meter telecom antenna at Huancayo, in the country's central highlands. It's the latest example of the enthusiasm for radio-astronomical recycling. As optical fiber cables supplant more dishes around the world, more universities and observatories might take advantage of a low-cost opportunity to commence or expand observations.

The refurbished instruments are limited in the frequencies they can observe, and that causes some controversy. Makoto Miyoshi, a radio astronomer at NAOJ, thinks Japan's labor power and financial resources should be dedicated to cutting-edge science. “I feel that there are too many radio telescopes in Japan,” he says. Hideyuki Kobayashi, another NAOJ radio astronomer, admits that 30-meter-class antennas are “banal.” But he notes that competition for limited observing time on more powerful instruments is intense. For a small university, an antenna can attract students, involve the community, and yield important results if research is carefully targeted. And for a developing country with few observational instruments, like Peru, an old radio antenna provides entry into astrophysical research and future regional VLBI projects, says Jose Ishitsuka, an astronomer heading the IGP project.

Radio astronomers are scavengers par excellence. Almost from the inception of NASA's Deep Space Network in the late 1950s, many of its antennas used for satellite tracking and communications have been available on occasion for radio astronomy. Over the years, NASA donated a number of older antennas to observatories. In Japan, three universities took over government antennas that previously used VLBI techniques to track crustal deformations in the earthquake-prone country.

Outmoded telecom antennas are the latest boon. In 1995, the University of Tasmania, Hobart, in Australia, acquired a 30-meter telecom dish in Ceduna, a town on Australia's southern coast about 850 kilometers west of Adelaide, and converted it into a radio telescope. In Japan in 2001, KDDI, an international phone service provider, donated a 32-meter antenna at its earth station in western Yamaguchi Prefecture to NAOJ, with management granted to Yamaguchi University. Then several years ago, KDDI started shutting down Ibaraki Earth Station and offered the two dishes to NAOJ and Ibaraki University. “We recognized [the antennas] would have a big impact on radio astronomy in Japan,” says Ibaraki radio astronomer Munetake Momose.

The gifts require some renovation. For starters, the frequencies often need to be retuned. Ibaraki University must address another challenge: Although the dishes move, they were designed to point at geostationary satellites. The Ibaraki team must install a star-tracking system, data recorders, and other electronics. If all goes smoothly, they will begin observations in the spring of 2010—at a bargain price. Refitting the Ibaraki antennas will cost about $1.2 million. Building two new 32-meter antennas would have run roughly$44 million, says NAOJ's Kobayashi. Conversion “is a nice business, isn't it?” he asks.

The deal gets sweeter after factoring in the scientific rewards. The Ceduna radio telescope extended the east-west spread, or baseline, of the five-station Australian Long Baseline Array, resulting in higher quality images of active galactic nuclei, pulsars and masers, says Simon Ellingsen, a radio astronomer at University of Tasmania. As a standalone telescope, it has carved a niche by making extended observations of radio sources that vary greatly over hours or months. “The monitoring is yielding many new insights and puzzles in relation to radio variability,” says Ellingsen. Among other things, the observations are helping sort out whether the sources are truly variable or if radio emissions are modulated by the interstellar medium near Earth.

In Japan, the Takahagi antennas will join seven others used to occasionally bolster the dedicated four-antenna VLBI Exploration of Radio Astrometry network. Training a denser array on a celestial object produces “a very clear image,” says Kobayashi. The Yamaguchi telescope is also concentrating on long-term observations; it has detected curious variability in radio emissions from Cepheus A, a well-known star-forming region, says Kenta Fujisawa, who heads Yamaguchi's radio-astronomy efforts.

Yamaguchi University has also used its antenna to build community relations. Each year, Fujisawa gives 10 or so public lectures at which attendees can remotely operate the dish for real-time observations. Yamaguchi Prefecture “has astronomy as a part of its culture now,” he says—not to mention a stellar commitment to recycling.

5. NEWSMAKER INTERVIEW

# Nancy Pelosi: Foursquare for Science

1. Jeffrey Mervis

As speaker of the House, Representative Nancy Pelosi (D-CA) provokes strong reactions. Republicans like to energize the party faithful by pinning her name to Democratic policies they oppose. But as far as most U.S. scientists are concerned, Pelosi can do no wrong as the leader of congressional Democrats.

Last week, at three events held within an 8-hour span on a single day in Washington, D.C., the community paid tribute to Pelosi's successful advocacy of bigger research budgets and, more broadly, the importance of supporting innovation in a time of economic turmoil. In turn, Pelosi told scientists they need to work even harder to sustain the gains made in the recent stimulus package, the 2009 spending bill, and the president's budget request for 2010 (Science, 6 March, p. 1274).

The host groups—the Task Force on the Future of American Innovation, the Coalition for National Science Funding (CNSF), and Research! America—delivered the same message at all three gatherings: Thank you for all that you've done for science, and keep up the good work. “We talked about the importance of steady and uninterrupted increases that at least keep up with inflation,” said Robert Berdahl, president of the Association of American Universities in Washington, D.C., who attended the task force event. “We wanted to thank the speaker … and to say that we wanted to be able to keep thanking her.”

Pelosi—who became the first woman speaker after Democrats captured the House of Representatives in November 2006—returned the favor, praising the scientific societies, university presidents, and industry leaders for their lobbying and reminding them that their work is far from over. “None of what we were able to do would have been possible without the mobilization of the outside scientific community,” she told the CNSF gathering. A few hours later, as she accepted the founder's award from Research!America, she told the assembled biomedical bigwigs that “we need your help again to make President Obama's executive order on stem cell research the law of the land.” The public is behind you, she assured both groups. “Every place I go, no matter what the audience, every time I say science, science, science, science—and I say it everywhere—the room bursts out in applause.”

Donning her mantle as party leader, she used the events to take a swipe at the Bush Administration. “For a long time, science had not been in the forefront. It was faith or science, take your pick. Now we're saying that science is the answer to our prayers.”

In the course of her “science day,” Pelosi agreed to field a few questions from Science. Here are her answers.

Q: Are you worried that pressure to reduce the budget deficit will ultimately force Congress to trim the president's 2010 request for science?

N.P.: If we make these investments in science, we will be able to remain leaders of innovation and stay number one in global competitiveness. For example, we will be able to improve health care. And that's the biggest way to reduce the cost of many entitlement programs. It will also help us become energy independent. So these investments will actually help us lower the deficit.

Q: Do you favor making foreign students with newly minted Ph.D.s from U.S. universities eligible for green cards?

N.P.: Yes, I'm for that—we want to staple a green card to those diplomas. And I think we have a chance to do it as part of a comprehensive immigration reform bill. But not on its own.

Q: You've talked about the importance of international benchmarking. Do we need a system of national standards in math and science, rather than the current patchwork system across all 50 states?

N.P.: We need to take a look at that. I have a great deal of confidence in two people—Congressman George Miller [D-CA], who's chairman of the education committee, and Bart Gordon [D-TN], who's chairman of the science committee. One of the reasons we were able to move some of our initiatives on science education so quickly was because George, who also has jurisdiction over higher education, said to Bart, “You just take the ball and run with it.” So between the two of them, I have confidence that they will be able to come up with something useful.

Q: Why has it been so hard to attract and retain minorities in math and science?

N.P.: One of the things we did in the [stimulus] package was to recognize that many of our historically black colleges and Hispanic-serving institutions have not been receiving the grants and whatever else they need because they don't have the facilities. So we tried to make them eligible for more funds, to build the facilities that will attract the scientists who will apply for the grants. And their success will attract students, which will lead to excellence. We've also talked to NIH and other agencies about the importance of getting scientists to address the health disparities in our country. But it's a real challenge.

Q: Will this Congress approve a permanent R&D tax credit for industry?

N.P.: Yes, I hope so. But we want it permanent, and we want it modernized.

6. SCIENCE EDUCATION

# New Texas Standards Question Evolution, Fossil Record

1. Yudhijit Bhattacharjee

New science standards for Texas schools strike a major blow to the teaching of evolution, say scientists and educators who last week tried unsuccessfully to block the adoption of last-minute amendments aimed at providing an opening for the teaching of creationism. The standards incorporate talking points from the intelligent design literature, including doubt that the fossil record provides convincing evidence of evolution. Supporters of the new standards, who prevailed on 27 March by a vote of 13 to 2, say the next step will be to press publishers to modify biology textbooks.

“I think the new standards are wonderful,” says Don McLeroy, chair of the Texas Board of Education and a dentist who claims that “dogmatism about evolution” has sapped “America's scientific soul.” McLeroy believes that biology texts, to meet the new standards, should include “an evaluation of the sudden appearance of fossils” and “an explanation of stasis or how certain organisms stay the same over time.” He also wants the textbooks to declare there is no “scientific explanation for the origin of life” and that “unguided natural processes cannot account for the complexity of the cell.”

McLeroy is anticipating the state's adoption in 2 years of new biology textbooks. Because Texas is the second-largest textbook market in the United States, publishers have a strong incentive to be certified by the board as “conforming 100% to the state's standards,” says Dan Quinn of the Texas Freedom Network in Austin, which has campaigned to keep creationism out of the science classroom. Quinn cited the example of a high school textbook on health education that was stripped of anatomical line drawings and references to sexuality and contraceptives before it was submitted for board approval in 2004.

Quinn and his colleagues thought they had won a major victory earlier in the 3-day meeting when the board voted to strike from the existing standards the requirement that teachers present the “strengths and weaknesses” of evolutionary theory. But the next day, conservatives won support for a similar phrase that calls on teachers to “analyze, evaluate, and critique scientific explanations in all fields of science by using empirical evidence, logical reasoning, and experimental and observational testing, including examining all sides of scientific evidence of those scientific explanations so as to encourage critical thinking by the student.”

The new language covers two hot-button topics. Teachers will now be required to have their students “analyze and evaluate scientific explanations concerning the complexity of the cell” and “analyze and evaluate the evidence regarding formation of simple organic molecules and their organization into long complex molecules having information such as the DNA molecule for self-replicating life.” Students will also be expected to “analyze and evaluate a variety of fossil types such as transitional fossils, proposed transitional fossils, significant fossil deposits with regard to their appearance, completeness, and alignments with scientific explanations in light of this fossil data.”

The creationists were “dogged,” says Eugenie Scott of the National Center for Science Education in Oakland, California. “It was like you put the stake in the heart of the vampire and it comes back.” Moderates on the board may have failed to recognize the final amendments as intelligent design talking points, she added, because they were focused on the “strengths and weaknesses” clause.

7. SCIENCEINSIDER

# From the Science Policy Blog

In Bonn, Germany, international negotiators to the U.N. climate change treaty began work this week on a successor to the Kyoto Accords, an effort they hope to finish by December in Copenhagen. “My team and I came here determined to make up for lost time,” top U.S. negotiator Todd Stern told delegates. The United States also hopes to hold bilateral talks with the 15 or so biggest emitters around the world. Meanwhile, stateside, a key draft of climate legislation was released this week in the House of Representatives by Edward Markey (D-MA) and Henry Waxman (D-CA).

British scientists and biomedical institutions have rallied to oppose portions of a new European Union animal-experimentation law. Animal-rights advocates have pushed the E.U. law, which would create new ethical reviews and tougher minimum housing and care requirements. British scientists told ScienceInsider that they fear the new regime will create a mountain of paperwork.

The U.S. National Institutes of Health (NIH) announced that $60 million of the$10 billion it has received as part of the stimulus package for spending to boost the economy will be set aside for a competition on autism research. In 2008, NIH spent $118 million on the disease, so that's a big increase. Most of the rest of the stimulus funds will be spent on proposals already in the hopper, but National Institute of Mental Health Director Thomas Insel says he hopes that the autism funding can be distributed in the next 18 months if proposals are good. Elsewhere … The blog offered regular updates on the Texas vote on science standards related to the teaching of evolution (left). It chronicled difficulties among the Irish science community to justify current funding in hard economic times and a new database of Japanese research. And it noted the frustration of some environmentalists that the Obama Administration, despite its green reputation, didn't endorse Earth Hour, an international effort to turn off the lights from 8:30 p.m. to 9:30 p.m. on 28 March. For the full postings and more, go to Science Insider. 8. CELL BIOLOGY # Overcoming Opposition, Brazil Banks on Stem Cells 1. Marcelo Leite* 1. Marcelo Leite is a writer in São Paulo, Brazil. SÃO PAULO, BRAZIL—Despite vocal opposition from religious groups, the Brazilian government has launched a major initiative in pluripotent stem cell research. In the past 3 weeks, eight university labs in four states started receiving the first payments of a 3-year,$9.3 million grant intended to reshape them into Cell Technology Centers.

The largest chunk, $2 million, will establish a National Laboratory for Human Embryonic Cells (LaNCE), split between the Federal University of Rio de Janeiro (UFRJ) and the University of São Paulo (USP). Run by Brazilian stem cell powerhouses Stevens Rehen in Rio and Lygia Pereira in São Paulo, the lab will create a national stem cell bank to supply lines of existing and newly derived human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells to Brazilian researchers by early 2010. In a predominantly Catholic country, the new stem cell initiative has not come easily. In 2005, Brazil's Congress passed the Biosafety Act, which allows the extraction of stem cells from surplus or nonviable human embryos stored for 3 years or more at in vitro fertilization clinics. But Catholic groups immediately challenged the legislation, claiming that embryos should have a constitutional right to life. A coalition of scientific groups, including the Brazilian Society for the Advancement of Science, and patients' advocacy organizations fought back. In May 2008, the Supreme Federal Court upheld the act. Leading the stem cell cause was Mayana Zatz, who works on muscular dystrophies at USP. Together with patients' groups, she helped fill the Supreme Federal Court galleries with people in wheelchairs and their relatives. Eduardo Campos, then the minister of science and technology, also got involved. The Department of Science and Technology within the Ministry of Health has identified stem cell research as one of its priorities. Since 2005, the ministry has spent$24.7 million—about one-tenth of its biomedical research budget—on stem cell research, funding some 40 labs. In October of last year, it selected eight labs to become Cell Technology Centers. LaNCE is the only center devoted exclusively to pluripotent stem cells, both hES and iPS.

So far, the government's investment has paid off with several key advances. In March 2008, Rehen's group succeeded in scaling up the culture of hES cells in bioreactors, spinning jars in which cells are grown attached to tiny beads while being continuously bathed in cell growth medium. Currently, most hES cells are cultured in tissue plates, a process that must be repeated many times over.

“Large-scale culture of hES cells is necessary for any country that has a hES cell bank,” says Jeanne Loring of the Center for Regenerative Medicine at the Scripps Research Institute in San Diego, California. “This is the first South American group to my knowledge that has achieved this, and given the short time frame in which hESC research has been supported in Brazil, this is an achievement that Stevens should be proud of.”

“It was kind of obvious to try bioreactors in scaling up the production of stem cells,” says Rehen, who adds that “our system was 100% developed in Brazil, although adapting already available techniques.” The system, which was developed in collaboration with UFRJ chemical engineer Leda Castilho, has already boosted production more than 70-fold at half the cost of plate cultures.

Seven months after Rehen's feat, in October 2008, Pereira in São Paulo derived the first hES cell line in Brazil, branded BR-1, from surplus embryos. Since then, her lab has differentiated these cells into muscle, neuronal, and pancreatic tissues.

Rehen's lab followed that last January with the first derivation in Brazil of iPS cells. Like hES cells, iPS cells have the potential to differentiate into all body tissues but can be made without the controversial step of producing and subsequently destroying embryos. Rehen used a modification of the protocol developed by Shinya Yamanaka at the University of Kyoto in Japan, who induced differentiated cells into a pluripotent state by inserting four genes.

With the $2 million in funding for LaNCE, Pereira will keep deriving hES cell lines from surplus embryos in her São Paulo lab, while Rehen will mass-produce them in Rio. They are also committed to training Brazilian investigators on hES cell techniques free of charge. By the beginning of 2010, they hope to have the capacity to produce 30 million pluripotent cells a month, certified free of chromosomal abnormalities and mycoplasm contamination. LaNCE plans to double the production after 450 square meters of refitted lab space become available. “If this works, it will be fantastic,” says stem cell researcher Zatz. “We do need specialized core facilities like those available in the U.S. and Europe, providing research goods for labs all over the country. But we also need steady long-term financing. Three years is not nearly enough.” Reaction from outside the country has been enthusiastic. “I truly applaud the Brazilian government for their investment in stem cell technology,” says Marie Csete, chief scientific officer at the California Institute for Regenerative Medicine in San Francisco. She and Loring would like to see the group derive iPS cell lines from the many ethnically diverse populations in Brazil to test whether drugs work the same way in different groups. In addition, she says, “iPS cells from patients in Brazil can be used to establish ‘disease in a dish’ models that will be available to screen drugs from the novel drug libraries in [their] country.” 9. SCIENCE CAREERS # Support for Tenure-Track Jobs in Biomedical Sciences 1. Beryl Lieff Benderly* 1. Beryl Lieff Benderly is a columnist for ScienceCareers.org. Many universities have cut back on hiring during the recession, making faculty openings scarcer than usual. To offset the chill, the U.S. National Institutes of Health (NIH) has announced a plan that it hopes will create up to 117 new tenure-track positions for young scientists starting this fall. “We heard about spectacular postdocs having trouble finding positions because there were so many searches being canceled,” says Jeremy Berg, director of the National Institute of General Medical Sciences, one of 14 centers and institutes receiving applications. The awards will provide lab start-up packages for 2 years, funded out of NIH's$10.4 billion share of the stimulus bill.

The P30 mechanism used for the competitive grant program—labeled “Biomedical Research Core Centers to Enhance Research Resources”—is, Berg admits, “unfortunately a bit obscure.” But it's in place. Devising a new mechanism, he says, would have taken too long to permit two full years of support within the recovery act's time frame—the money must be spent by the end of fiscal 2010. Confusion about the program proved to be so great that on 27 March—3 days after the announcement was issued—NIH took it down, promising to post a new notice soon. “It's just [a matter of] clarifying the language,” Berg says.

But those increases do not begin to cover what NASA's science program needs just to keep pace with the demands of researchers. The agency's science honcho, Edward Weiler, says he needs $900 million more every year just to keep up with current earth science projects. “There is no greater thing than starting a new, sexy science mission,” he says. “We all love it. The thing that prevents me is I've also got new, sexy missions started 5 years ago that are costing more than they were supposed to.” ## Back to the future Complaints about overruns in the science program extend back to at least 1980. Back then, however, NASA's entire budget equaled that of its science budget today. And today, there's a much longer line of telescopes, planetary robots, and Earth-monitoring satellites waiting to be designed, built, and launched. ## Online Extra Read an interview with Ed Weiler on his plans for managing NASA's huge science program. That queue, ironically, is due in part to the success enjoyed by scientists in plotting their future. Since the 1960s, astronomers have created a consensus decadal plan for the next generation of telescopes. Earlier this decade, the other three disciplines that depend heavily on NASA dollars—earth sciences, solar system exploration, and solar studies—followed suit. Providing the space agency with a clear set of missions and their costs has helped scientists make their case with members of Congress and NASA bureaucrats. “I'm a slave to the decadals,” says Weiler. But that community process relies on accurate cost estimates. And when the costs soar, the process breaks down. The most infamous example is the James Webb Space Telescope, which astronomers pegged at$1 billion, not including operations and launch, in a 2001 report. The true cost likely will top $4 billion by its launch in 2013, forcing NASA to slow down work on a slew of other astronomy and astrophysics missions. Weiler headed the space program from 1998 to 2004 before becoming director of Goddard Space Flight Center in nearby Greenbelt, Maryland. Last April, he was called back downtown to run the program after S. Alan Stern quit in a funding dispute with then-Administrator Michael Griffin, who left NASA in January. Stern made cutting costs his mantra, and he played hardball with project managers and contractors. But Stern also failed to win advocates for his cause and departed after only 12 months on the job. “When I walked into this office, there were a lot of promises made out there, and communities were pretty happy,” Weiler said in a recent interview at NASA headquarters. But within days, he says, a team of independent cost reviewers gave him the bad news. “Over a 10-year period there were$6 billion of promises made [in planetary sciences] that could not be met. And so I was put in the position of being the bad guy.”

In the past, human space flight often tapped science to pay for its own shortfalls. This time around, however, the problem is within the science program—too many missions costing too much money. For example, technical difficulties led to a $400 million cost overrun on the Mars Science Laboratory (MSL), which forced Weiler to postpone its launch by 2 years. The decision pushed back other planned Mars flights. Mars wasn't the only trouble spot. Few missions in either the solar studies or the earth sciences program were on budget and schedule. The Solar Dynamic Observatory (SDO), a Goddard effort to investigate the sun's magnetic field, is close to 2 years behind schedule and its initial estimated budget has tripled. The Glory spacecraft being prepared to study aerosols and black carbon in Earth's atmosphere was more than 50% over its original$266 million price tag, and its 2008 launch has been postponed until at least the middle of 2009.

Such problems have triggered a round of finger-pointing. In 2007, nearly 100 earth scientists warned that the global monitoring system for understanding climate change was “at risk of collapse” because of NASA's failure to promptly move ahead with its projects. Last month, solar scientists complained that nearly all of their proposed decadal missions have been delayed or deferred.

Weiler, in turn, blames the science community for its unrealistically low initial projections. “Scientists cannot do cost estimation,” he says. He notes that their numbers typically come from NASA centers, which assume that a low estimate will make the project more politically viable. “I won't call it lying or cheating,” says Weiler. “It's optimism.”

Such criticism doesn't sit well with those who took part in the decadal studies, most of which were completed during Weiler's first stint as science chief. They defend their efforts and resent what they see as his Monday-morning quarterbacking. “We got independent cost estimates as well as numbers from NASA—and added 10% to 20% as a fudge factor,” says Louis Lanzerotti, a physicist at the New Jersey Institute of Technology in Newark and a member of the 2003 decadal panel for solar studies. “We had tremendous cost awareness.” Lanzerotti says his team worked hard “to make sure our report was credible.”

Joseph Alexander, a former director and current officer of the Space Studies Board at the National Academies, which oversaw the reports, says estimates have gotten better since the infamous James Webb episode. But he believes that even the solar decadal—the last of the four to be completed—“still didn't have a rigorous process.” The next round of decadal studies will feature a much more rigorous cost analysis, he says, aided by engineers and managers with extensive experience in putting spacecraft into orbit. At the same time, none of the missions chosen for the previous decadal study will be grandfathered into the new study. “Anything not in the works gets thrown back in the hopper to be recompeted,” he warns.

## No quick fix

Even as the decadal panels try harder, so too must NASA, according to independent reports presented at the 5 March congressional hearing. The Aerospace Corporation, a nonprofit organization in El Segundo, California, found that only five of 40 NASA missions—mostly to do science—came in on time and on schedule, and that more than a quarter were at least 40% costlier than anticipated. Spacecraft grew an average of 40% heavier by final design. (Weight is a critical factor in boosting the cost of a mission.) And when one project goes over budget, “the resulting domino effect impacts all missions that follow,” noted Aerospace Corporation Vice President of Civil and Commercial Operations Gary Pulliam at the hearing.

The Government Accountability Office (GAO) reported similar results. The congressional watchdog found that costs for 18 projects, the bulk of them science missions, grew by an average of 13% within 3 years—one rose by 50%—and were delayed by nearly a year. The study faulted NASA for moving a program into development before it has a stable design and for assuming that new projects will save money by drawing on the technology of previous missions. “Time and costs were consistently underestimated,” says GAO's Cristina Chaplain.

Acting NASA chief Chris Scolese confessed to the House panel that the agency's ability to pinpoint cost and schedule issues have been “less than desired in the past” and described early estimates as “at best, educated guesses.” But extending the lifetime of successful missions is also a factor, he said, because it shrinks the pot of money available for new efforts. In the agency's defense, Scolese said NASA had no control over overruns and delays on half of the 10 projects cited in another GAO report. SDO, for example, has had to compete with commercial and military customers for an Atlas launcher. NASA officials say there was no way to predict the sudden paucity of launchers.

The root of the problem, say several scientists who declined to be quoted for fear of retribution, is an iron triangle among NASA centers, lawmakers, and contractors. “There is a lot of fat at the centers,” says one researcher with years of experience on NASA science missions. Adds another: “Industry, academia, and the centers all know that NASA headquarters folds on the issue of cost overruns.”

Weiler disputes that assessment. “If you think we don't get mean with contractors, go talk to some of the CEOs who've gotten an earful from me,” he says. And he did kill more than a half-dozen projects in their early phases during his previous tenure as science chief. But the big savings would come from canceling missions under construction, a step that requires taking on that iron triangle. Goddard's SDO, for example, has won consistent backing from Senator Barbara Mikulski (D-MD) despite the cost increases, and the large and influential California delegation protects efforts such as MSL based at NASA's Jet Propulsion Laboratory in Pasadena. The desire to preserve high-tech jobs is especially strong during economic downturns.

Weiler suggests that such increases come with the territory. “Can we forget that Hubble overran 300%?” he asks. “It's the greatest success in NASA history, but I could give you a list of prominent people in the community who wanted Hubble killed during its development. I won't, because it turns out many of them made a career off the Hubble data.”

Many space scientists agree with Weiler that most of NASA's greatest science accomplishments suffered cost overruns and that such increases are unavoidable for unique missions. But will a new NASA chief try to shake up the current system in search of a better approach? That's what scientists planning to choose what projects matter most to them for the coming decade are anxious to find out.