News this Week

Science  24 Sep 2004:
Vol. 305, Issue 5692, pp. 1882
1. SPACE SCIENCE

Rising Cost of Shuttle and Hubble Could Break NASA Budget

1. Andrew Lawler

Science may have to pay a steep price for putting the space shuttle back in business. Last week, NASA science chief Al Diaz ordered his managers to find at least $400 million in cuts to space and earth science efforts so that the space shuttle could resume flying in 2005, according to NASA officials. Billions of dollars in unexpected shuttle costs also threaten aeronautics and the nascent exploration effort. The crunch comes only 7 months after President George W. Bush proposed an ambitious new trajectory for the space agency that officials said would not strain NASA's budget. Finishing the space station and closing down the shuttle program early in the next decade would free up money for lunar and martian robotic and human missions, they explained. Under that plan, spending on science would grow from$4 billion in 2004 to $5.6 billion in 2009, while shuttle spending would drop from$4 billion to $3 billion. But the expected cost of fixing the shuttle fleet, grounded since the loss of Columbia over Texas on 1 February 2003, has soared to at least$2.2 billion. At the same time, NASA is also scrambling to find a similar amount for a robotic mission to the ailing Hubble Space Telescope. Worst of all, neither the White House nor Congress seems willing or able to rescue the agency.

The White House rebuffed a recent plea by NASA Administrator Sean O'Keefe for additional funding to cope with the agency's fiscal crisis, Administration sources say. And the president's 2005 request has received a rocky reception from a Congress faced with a massive budget deficit and the war in Iraq. “There isn't the money to mount an aggressive exploration program,” says Malcolm Peterson, former NASA comptroller. “And if there isn't budgetary relief, I don't know where else you go [for funding] except science.”

To fly the shuttle safely again, NASA will need as much as $760 million for next year alone, says Steven Isakowitz, NASA's current comptroller. Privately, agency managers expect the figure to rise to$1 billion for the 2005 fiscal year that begins next week and remain at that level for the next few years. To cope, NASA managers are being told that science must pony up approximately half of that shortfall, with the rest coming from aeronautics and exploration. Diaz, who assumed the job in August as part of an agency reorganization, declined to be interviewed. Agency spokesperson Donald Savage said Diaz was “uncomfortable” discussing budget matters.

The agency already wants $866 million more to start the exploration program in the coming year. That effort includes work on a lunar orbiter, a sophisticated nuclear electric system for interplanetary trips, and a large launcher to replace the shuttle. The Senate funding panel that oversees NASA this week approved$15.6 billion for the agency in 2005, only $200 million more than this year's figure and far short of the Administration's request of$16.2 billion. Still, that tops the House level of $15.2 billion, and some senators were hoping to add another$800 million when the bill reached the Senate floor this week.

“There is no doubt whatsoever that whatever we choose, we'll have to make difficult decisions,” says Isakowitz. “And that includes science, aeronautics, and exploration” programs. Anything short of the president's request, he says, would have a “negative” impact on science.

But even if Congress obliges, NASA will remain in a deep budget hole. O'Keefe was clear at an 8 September Senate hearing that science and exploration for now must take a back seat to human space flight. “Agenda number one is return to flight and complete the station,” he said.

Many lawmakers are impatient with the ballooning shuttle costs. Senator Sam Brownback (R-KS), who chairs the Senate panel that oversees NASA's programs, insists that the answer is to phase out the shuttle as soon as possible. He told Science that “the Administration has just got to walk away from the shuttle more quickly.” Proposals to do that include using cheaper, expendable launchers or reducing the number of solar panels and reorienting the station's current position in orbit. Those options would not sit well with NASA's international partners, however, and O'Keefe told the Senate committee that “I don't see a really significant diminution of the flight rate.”

The second huge and unplanned price tag facing NASA is for robotic servicing of Hubble. O'Keefe has rejected sending astronauts to conduct the mission. A recent study by the Aerospace Corp. for NASA put the cost of a “Cadillac” mission to replace dying batteries and critical instruments at $2.2 billion. That figure is far higher than an earlier estimate by NASA's Goddard Space Flight Center in Greenbelt, Maryland, which put the price tag at$1.3 billion. Other NASA officials say privately that at least $2.4 billion is needed. Even with ensured funding, however, a complex robotic mission is a race against time. The Aerospace Corp. study predicts that the Cadillac effort would take 5.4 years, and NASA engineers fear that Hubble could shut down as early as 2009. Goddard managers believe they could launch such a mission by December 2007, but an internal NASA study found that date too optimistic by 2 years. A shuttle mission could be ready in 2.5 years, says Michael Moore, a Hubble program executive. But that, NASA insists, would cost$200 million more than the Cadillac robotic mission.

Cheaper options include a simpler effort to deorbit the giant telescope safely, which NASA estimates would cost as little as $400 million. Some researchers and engineers want NASA to build a “Hubble-lite” that would incorporate the new instruments already waiting to fly. Despite their claim that the new mission would cost less than$1 billion, NASA is not seriously considering this option.

Given the tough budget environment, Administration and congressional sources say some programs inevitably will face the ax in 2005. One likely target is the multibillion-dollar Prometheus program to build a new nuclear electric power system (Science, 30 January, p. 614). The scrapping of the Prometheus program would be a big blow to planetary scientists, who are depending on that system to power the Jupiter Icy Moons Orbiter in the next decade. “I don't think we're facing cancellation,” says Craig Steidle, chief of NASA's new exploration effort. But he acknowledges that reductions could force changes to Prometheus. There are no plans to cut work in the biological and physical sciences, says Steidle, who also oversees those programs.

Scientists inside and outside the agency will be watching closely to see whether O'Keefe can convince Bush and Congress to provide relief or whether research must be sacrificed for the shuttle and Hubble. “It's all very difficult and confusing,” says one NASA manager. “How the heck is the agency going to fix this?”

2. NATIONAL SCIENCE FOUNDATION

President Reverses Course, Taps Bement as Director

1. Jeffrey Mervis

According to court documents, Dekich asked for Rosenberger's help in 1998 in identifying the subtype of avian influenza afflicting his company's chicken flocks. After receiving the sample, Rosenberger asked one of his lab employees to ship it to a U.S. Department of Agriculture lab in Ames, Iowa, labeling it as an isolate obtained from Delaware. The federal lab identified the virus as subtype H9N2—a strain not known to be fatal to humans. After doing work on its sample, MBL shipped two batches of the vaccine to the Saudi company for $850,000, falsely labeling them as a vaccine for Newcastle disease. The microbiologist's offense “was serious in that it knowingly introduced a pathogen into the country that could endanger commercial flocks,” says George Dilworth, assistant U.S. attorney for Maine. “Anybody in a similar position should know they risk serious repercussions if they engage in such conduct.” Rosenberger's prosecution is yet another warning that researchers must pay closer attention to regulations governing the handling of microbial samples, says Janet Shoemaker, director of public affairs at the American Society for Microbiology. “There is good reason for the government to be concerned about such violations from the public health point of view,” she says. The University of Delaware says it wasn't aware of the case before Rosenberger pleaded guilty but that it has since begun an audit of laboratory procedures. Rosenberger is currently on leave and is due to retire in January after 23 years at the university. 5. DOE LABS Firing Draws Protest at Los Alamos 1. David Malakoff, 2. Charles Seife A senior scientist fired this week by Los Alamos National Laboratory (LANL) as part of a response to long-standing safety and security problems says he will contest his dismissal. The scientist is one of a dozen workers punished in what Director G. Peter Nanos called a move to restore public “trust and confidence” in the lab and “exercise control over our own destiny.” “We will challenge the [firing] … and try to get it reversed or reduced,” says David Cremers, an award-winning laser researcher and 24-year lab veteran who was involved in a laser accident earlier this year that injured an intern. The incident was one of several safety and security lapses that in July prompted Nanos to suspend 23 employees and shut down all work at the 12,000- employee lab in New Mexico (Science, 23 July, p. 462). The controversial decision, which has cost LANL millions of dollars per day, came just as the University of California was gearing up to defend its contract to manage the lab for the U.S. government. Last week, in an e-mail to lab staff, Nanos announced that he was firing four workers, punishing seven others, and awaiting one resignation. One worker was still under investigation, he wrote, and 10 others had been cleared of any wrongdoing. Lab officials would not identify the punished workers but told reporters that three were involved in a July incident in which officials concluded that computer disks holding classified data were missing from a safe in the lab's Weapons Physics Directorate. Politicians briefed on the case say it now appears that the missing disks never existed and were the product of sloppy record-keeping. Science has learned the names of those involved in the laser accident, however. In addition to firing Cremers, LANL is negotiating the resignation of chemist Thomas J. Meyer, the lab's associate director for strategic research and a member of the National Academy of Sciences. Meyer declined comment. According to a lab investigation report, the 14 July accident occurred as Cremers was demonstrating to a female undergraduate student a dual-laser technique for vaporizing and analyzing soil samples. With the intern out of the room, Cremers fired one laser to suspend soil particles in a target chamber. Then, with the laser on a nonlasing setting, he invited her back into the room to view the particles. The laser burned a nearly half-millimeter hole in the intern's retina as she bent over the target, damaging her vision. The report concluded that the researchers were not wearing the required eye protection and had ignored other safety rules. “I will have responses to some of the committee's findings,” Cremers says. Both sides seem to agree that there is no obvious explanation for how the laser fired. Nanos, meanwhile, says the punishments mark a new era, and officials say the entire lab should be back to work by next month. “We are not the old Los Alamos anymore,” he said at a 17 September all-hands meeting. But one LANL researcher says the turmoil has put morale “near rock bottom. Some of us are looking for the exits.” 6. EUROPEAN PATENTS Stem Cell Claims Face Legal Hurdles 1. Gretchen Vogel Researchers hoping to sew up rights to discoveries involving human embryonic stem (ES) cells in Europe are facing an uphill battle. In recent months, the European Patent Office (EPO) has rejected two applications involving human ES cells and limited a third, arguing each time that the patents would violate the European Patent Convention, which prohibits the industrial or commercial use of human embryos. The decisions are subject to appeal, but the initial rulings signal a wide gap between policies at EPO, which issues patents valid in its 28 member countries, and those of the U.S. Patent and Trademark Office (USPTO), which has granted dozens of patents involving cells derived from human embryos. The recent cases include one of the fundamental patents in the field, filed by James Thomson of the University of Wisconsin, Madison, and granted in 1998 by USPTO. It covers the techniques used to derive primate ES cells—including those from humans. On 13 July, EPO rejected the application; the patent's owner, the Wisconsin Alumni Research Foundation (WARF), filed an appeal earlier this month. The first clue to the office's reluctance came in 2002, when an EPO review panel ruled on a controversial patent involving genetic markers used to identify stem cells. The panel decided that any claims involving human ES cells violated the European Patent Convention (Science, 2 August 2002, p. 754). At the hearing, the patent holders, the University of Edinburgh, U.K., and Stem Cell Sciences of Melbourne, Australia, agreed to strike all references to human ES cells, but they have since decided to appeal. George Schlich, a patent attorney handling the case, says that although the remaining claims are useful, the owners thought it was worth asking EPO to reconsider. “It's a big enough point to merit being considered at a higher level,” he says. “Lots of people would have been disappointed if it were left there.” In the meantime, before the appeal is heard, EPO patent examiners are taking the review panel's decision as a precedent. Citing the Edinburgh decision, examiners have rejected the WARF patent as well as an application from David J. Anderson of the California Institute of Technology (Caltech) describing a method to isolate neural stem cells from embryonic tissue. The university appealed the decision in March. A third application from Oliver Brüstle of the University of Bonn on a method to differentiate neural cells from mammalian ES cells is still under review, but examiners at hearings in August expressed doubts about claims involving human ES cells. “It appears the Edinburgh decision is being applied uniformly by the examiners,” says Julian Crump of the law firm Mintz Levin in London, who represents Caltech in the Anderson case. Siobhán Yeats, director of examination in biotechnology for EPO, says that although the recent decisions are consistent, final policy “is still in flux” and will be decided by the EPO boards of appeal. She said a decision on the Edinburgh appeal is unlikely before late next year. The recent decisions probably will not slow the pace of basic research, Crump says, but they will have a chilling effect on any European biotech companies that might have considered investing in embryo-related cell technologies. Biotech companies in general depend strongly on patent protection for their initial worth, he notes, adding, “so to be asked to put it all on ice for a year or two or three, it's extremely difficult.” Determined applicants could still turn to individual countries to guard their intellectual property. Several EPO member countries, including the U.K. and Germany, have more lenient policies. The British patent office has specifically said that methods involving already existing embryo cells are patentable, and the German patent office granted Brüstle a patent in 1999. 7. SETTLEMENT OF THE PACIFIC Heaven or Hellhole? Islands' Destinies Were Shaped by Geography 1. Erik Stokstad When Polynesians spread across the Pacific, some flourished in what became island paradises. Others deforested the islands they colonized and, as on Easter Island, sank into warfare and cannibalism. Archaeologists have long wondered what went wrong. Now a unique, Pacific-wide analysis teases out the environmental factors that stacked the deck against some colonists. “It's a nice step forward,” says archaeologist Patrick Kirch of the University of California (UC), Berkeley. “They are hitting on some key factors.” Archaeologists had studied many of those factors—including rainfall, size of landmass, and degree of isolation—for a few islands, says ecologist Peter Vitousek of Stanford University. But none had taken such a broad, quantitative look. “It's an original and valuable approach,” he says. The work, by archaeologist Barry Rolett of the University of Hawaii, Honolulu, and geographer Jared Diamond of UC Los Angeles, began after Diamond asked Rolett why the Marquesas, unlike Easter Island, had kept their forests. Rolett has worked in French Polynesia for 20 years, examining Polynesians' environmental impact, with a focus on the Marquesas, 1200 kilometers east of Tahiti. But Diamond's question inspired him to cast a wider net. To answer it, the pair examined 69 islands across the Pacific. Rolett combed through the journals of early explorers such as James Cook to estimate how well forested the islands were at the time of European contact. For each island, they also quantified a range of environmental variables that might make forests fragile or resilient. After crunching the numbers, the two discovered what mattered most: Warmer, wetter islands were more likely to have resisted deforestation, as were big islands, islands whose high, rugged terrain made it hard to grow crops, and those dusted regularly with soil- enriching volcanic ash. The model, described this week in Nature, suggests that the troubles of Easter Island's colonists weren't entirely their fault. “They were in one of the most challenging situations, on one of the most environmentally fragile islands,” Rolett says. (The only islands more fragile were deforested and abandoned before European contact.) Easter Island's isolation was also a factor, the researchers concluded, by making it less likely that domesticated plants could have survived the voyage. None of the most important food trees, such as breadfruit, made it to Easter Island, for example, forcing the colonists to rely on less sustainable slash-and-burn agriculture to grow bananas, sweet potatoes, and sugar cane. In addition, fires used to clear land could easily spread from fields to forests on a small, dry island like Easter. In contrast, the equally small and dry Marquesas had retained their forests better than the model predicted because the Polynesians there cultivated breadfruit trees, Rolett says. (An island saying goes: “Plant a breadfruit tree when a child is born and no one will ever starve.”) With forests providing the main source of food, Marquesas islanders had no need to turn to slash-and-burn agriculture to sustain a growing population. Even today, the Marquesas retain more than half of their precontact forest cover. 8. RUSSIAN SCIENCE Academicians React Angrily to Draft Reform Plan 1. Andrey Allakhverdov, 2. Vladimir Pokrovsky* 1. Andrey Allakhverdov and Vladimir Pokrovsky are writers in Moscow. MOSCOW—After obtaining a leaked document last week, members of the Russian Academy of Sciences (RAS) erupted in an angry discussion about what many viewed as a government plan to slash the research establishment. At a meeting of the RAS presidium here on 14 September, president Yuri Osipov chaired a session on plans—in the works for more than a decade—to trim Russia's network of science institutions. Some argued that the new proposal would eliminate all but 200 of Russia's scientific institutions, including most of RAS's 454 affiliates. Osipov at first suggested that the group avoid discussing the unofficial document. But RAS vice president Nikolay Plate criticized the reform effort, saying it was designed to take the academy's property. However, a spokesperson said RAS has no plan to send comments on the document to the ministry of science and education. Andrey Svinarenko, Russia's deputy minister of science and education, confirmed that the paper reflected a presentation he made to the ministry's council. But he argued that it was a reasonable plan, noting that the number of research organizations in Russia has doubled since the 1990s to at least 5000. Svinarenko said that many of these are small, with three to 15 staff members, making them ineffective and costly to maintain. The draft plan would set a new standard: To receive government research funds, an organization would have to devote at least 35% of its output or services to research or technology development. Any that fail would have to find private money and integrate with universities, be sold, or close down. Former science minister Vladimir Fortov, now chief of an RAS division, says the reform agenda reflects “an old idea” held by some officials that “there is too much science in Russia.” He claims that some “want to eliminate most of our scientific institutions,” with a goal of spending money on innovation centers. “The goal is good,” Fortov says, but should not be pursued at the expense of basic science. “Innovations must be funded by those who are interested in them, not the government.” The best reform would be to support those who continue to do basic research, despite poor funding, low salaries, and lack of equipment. Svinarenko insists that reform would not damage RAS. But he argues that the government needs to create a nucleus of modern and well-equipped organizations—and that it must concentrate its resources. 9. VACCINES Rotavirus Vaccines' Second Chance 1. Leslie Roberts Two new vaccines against a major cause of deadly childhood diarrhea are nearing the market. Will the entire effort crash and burn as spectacularly as it did 5 years ago? In 1998, the world was poised to launch a major assault on one of humanity's deadliest childhood scourges. After years of development work, Wyeth-Lederle Vaccines and Pediatrics introduced into the United States a long-awaited vaccine to prevent the most common cause of severe, dehydrating diarrhea: rotavirus infection. It quickly became part of the routine immunization package. Within the first 9 months, more than 600,000 infants received drops of the live vaccine, and the company was eyeing potential U.S. sales of more than$300 million a year. Public health agencies around the world were equally ebullient: If they could get the vaccine into the poorest countries, where roughly 85% of deaths from rotavirus gastroenteritis occur, they could save perhaps a half-million lives a year.

Then came a devastating setback. In summer 1999, the U.S. Centers for Disease Control and Prevention (CDC) reported a rare but alarming association between the vaccine and a potentially fatal bowel obstruction, called intussusception. Wyeth immediately pulled the vaccine, RotaShield, from the market, amid consensus that the risk, then pegged at 1 in 2500 children immunized, was far too great in the United States, where diarrheal deaths are exceedingly rare.

The move dashed hopes of using the vaccine in developing countries—even though, with 1 in 200 children there dying of rotavirus diarrhea each year, the benefits would have greatly overwhelmed the risks. “A rare event in the United States meant the world would not get the benefit,” said Roger Glass, a longtime rotavirus researcher and head of the viral gastroenteritis section at CDC, at a recent meeting in Mexico City.* “It challenged our vision of equity.”

Now the global medical and scientific community has a second chance to get it right. Two new rotavirus vaccines are in the final stages of clinical trials, and evidence so far suggests they are safe and effective. The manufacturers, GlaxoSmithKline Biologicals (GSK) in Belgium and Merck & Co. in Whitehouse Station, New Jersey, are bullish; GSK plans to introduce the vaccine first in Mexico in 2005. The Global Alliance for Vaccines and Immunizations (GAVI)—created to strengthen immunization in developing countries—is throwing its money and clout behind the vaccines, and various public health agencies are subsidizing clinical trials. This private-public venture is being heralded as a model for how to accelerate the introduction of other, badly needed vaccines to the poorest countries of the world.

Yet, despite all this heart, muscle, and money, success is far from ensured. First, both companies want to recoup their substantial investments—$500 million for GSK and perhaps$800 million to $1 billion for Merck. How can they do that and offer the vaccine at an affordable price in poor countries? The RotaShield debacle has also left a legacy of doubt and uncertainty that will require additional testing, and time, to dispel. Complicating matters, the disease itself—rotavirus gastroenteritis—is hardly a household word, and health ministers may not be willing to spend scarce dollars to fight something they have never heard of. Then there are nagging doubts about whether a live oral vaccine based on one attenuated strain (the GSK product), or several (Merck's), can protect against the bewildering array of rotavirus serotypes, or varieties, some of which have just recently been detected. Both manufacturers insist they can. Finally, although the vaccines have done well in trials in Europe and Latin America, their effectiveness where they are needed most—in the poor-est parts of Asia and Africa—has yet to be demonstrated. The world may have a second chance, but the stakes are high, and a second failure would be a crushing blow. Ubiquitous and deadly Highly contagious, rotavirus hits hard and fast. Within 18 to 24 hours of exposure, children develop fever, violent vomiting, and diarrhea that, if left untreated, can quickly lead to death. In severe cases, the only recourse is intravenous fluids. The virus is also ubiquitous; all children everywhere are infected in the first few years of life. But its toll varies enormously. In the United States, rotavirus gastroenteritis causes an estimated 70,000 or more hospitalizations a year, a half-million doctor and clinic visits, and 20 to 40 deaths. In poor countries, however, where children may be undernourished, suffer from multiple gastrointestinal infections, and lack ready access to a hospital, the virus is far more deadly. Exactly how dangerous is tricky to pin down, though, as physicians rarely test for it. Until recently, the estimate was that rotavirus infection causes about 22% of all severe cases of diarrhea, accounting for about 440,000 of the 1.56 million deaths from diarrhea each year. But new surveillance data from an international effort to gauge the disease burden suggest that's a gross underestimate. As CDC epidemiologist Umesh Parashar reported at the Mexico City meeting, rotavirus was detected in 60% of stool samples from children hospitalized with severe diarrhea in Vietnam; 41% in China; 56% in Myanmar; and 29% in Hong Kong. Based on those and other data, Parashar and colleagues now estimate that rotavirus accounts for 39% of all cases of severe diarrhea, which translates into 608,000 deaths worldwide each year, mostly in children under age 1 or 2. After studying the disease for decades, Glass had expected few surprises from the surveillance data, but “the results blew us away,” he says. In the United States as well, asserts Paul Offit, chief of infectious diseases at Children's Hospital of Philadelphia, Pennsylvania, and one of the developers of the Merck vaccine, prevalence is vastly underestimated. “It's the second most common reason kids come to the hospital in the winter in Philadelphia,” he says. “The disease is a big deal in the United States.” Abrupt demise, long recovery Because very few children die of rotavirus gastroenteritis in the United States, some people were skeptical that RotaShield would be profitable. Yet despite the steep cost ($38 for each of three doses), the vaccine had a huge—and brief—success.

Its downfall began on 16 July 1999, when CDC reported 15 cases of intussusception—a rare defect that makes the bowel fold like a telescope—associated with the vaccine. If recognized early, the obstruction can be surgically treated, but it can be fatal. The risk, originally pegged at 1 in 2500 children immunized, or 1600 excess cases of intussusception a year, was deemed unacceptable in the United States, where only 1 in 100,000 children die of rotavirus infection. CDC withdrew its recommendation, and Wyeth pulled the vaccine in October 1999.

The decision sparked an outcry among international health experts, who felt deprived of a potent weapon. Albert Z. Kapikian, one of the developers of RotaShield at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), argued for a permissive recommendation that would enable U.S. physicians to use the vaccine at their discretion. That would have sent a powerful message to developing nations, he says, and perhaps spurred its adoption there. “But it fell on deaf ears,” says Kapikian. When the World Health Organization (WHO) held a pivotal meeting in 2000 to assess whether and how developing countries might introduce RotaShield, health ministers gave it thumbs-down. “They said they didn't want their population to be seen as second-class citizens. If it was not good enough for U.S. kids, it was not good enough for their infants either,” recalls Kapikian.

RotaShield's demise prompted some soul-searching at Merck and GSK, both of which had already invested millions in their rotavirus vaccines. In the end—with some encouragement from WHO, CDC, and other public health agencies—both decided to proceed, gambling that their vaccines would be safe and profitable and taking very different paths both scientifically and commercially.

Both efforts got a boost in 2002 when GAVI declared rotavirus vaccines one of two priorities and gave the new Rotavirus Vaccine Program (RVP) in Seattle, Washington, $30 million over several years to speed their introduction to the poorest countries of the world. Tore Godal, GAVI's executive secretary, argues that the world can no longer accept the status quo, when a lifesaving vaccine is introduced first in the United States but doesn't make it into developing countries for 20 years or more: “We've really got to reduce that gap.” For GSK and Merck, the first order of business has been to show that their vaccines do not trigger intussusception—a task that turned out to be hugely complicated. No one knows why RotaShield caused intussusception, although the link is real, concedes Lone Simonsen, an epidemiologist at NIAID. The oral live vaccine was made by combining three human rotavirus serotypes and one rhesus serotype. In retrospect, some suspect that the simian virus was the problem. Whatever the cause, since the vaccine was withdrawn, several studies have suggested that its risk was far lower, around 1 in 10,000. In Mexico, Simonsen reported unpublished data suggesting the risk would be as low as 1 in 40,000 if the vaccine were administered in the first 2 months of life, before intussusception from natural causes begins to rise. But that good news presents a quandary: Trying to prove the absence of a very small risk has forced the companies to conduct some of the most massive and expensive clinical trials ever undertaken. Merck's phase III trial involves 68,000 subjects and counting, mostly in the United States and Finland, with smaller numbers in nine other countries; GSK's phase III trial has enrolled more than 63,000 in 11 Latin American countries and Finland. Both are being watched closely by independent safety panels that would halt the trials if they saw an increased risk of intussusception. To John Wecker, who runs RVP from the Program for Appropriate Technology in Health (PATH) in Seattle, the ongoing trials bode well: “The companies are moving forward. I assume they have judged the risks acceptable.” Offit is encouraged that neither of the new vaccines seems to cause the mild side effects associated with RotaShield, such as fever and vomiting, much less intussusception. “It is unlikely they will,” he adds, because the new vaccines are “so biologically different” from RotaShield. (Merck's is a human-bovine reassortant, and GSK's is a monovalent human vaccine.) Even so, he adds, “we won't be convinced until we give it to several million kids.” Both Merck's Penny Heaton and GSK's Beatrice de Vos agree they can't rule out a risk conclusively until the vaccines are approved and tracked in large postmarketing studies. And should the two new vaccines be found to pose a small risk, most experts would still recommend their widespread adoption in developing countries. “It is imperative that we rethink the risk-benefit equation,” said Offit at the meeting. But will they work? Data so far indicate that both the GSK and Merck vaccines offer strong protection against severe disease in the United States, Europe, and Latin America. But it is unclear whether those results hold in other parts of the world. There are two issues. One is cross-protection. Ideally, a vaccine should protect against the well-known and emerging strains of rotavirus. Glass is particularly concerned about serotype G9, which ongoing surveillance efforts show is becoming increasingly important across Asia, and G8, gaining prevalence across Africa. “We didn't even know G9 existed when these two vaccines were designed,” he says. Both companies express confidence that their products will be broadly effective, although they are banking on very different scientific strategies. GSK went with a monovalent human vaccine, explains de Vos, director of clinical development, because it mimics the natural immune response that follows initial rotavirus infection. Infants are repeatedly exposed to a variety of strains of rotavirus, but only the first one or two episodes develop into life-threatening disease. GSK's vaccine, Rotarix, is based on an attenuated version of the prevalent G1 serotype. At the meeting, de Vos reported that Rotarix has shown significant protection against G1 and non-G1 types, including G9. “There is clear cross-protection,” agrees Glass, who has seen GSK's preliminary data. “But its efficacy against a full range of strains, especially G2, remains to be demonstrated.” The same is true for Merck's human-bovine vaccine, RotaTeq, which contains the five serotypes that account for some 75% of the global burden: G1, G2, G3, G4, and P1. Again, says Glass, there is good evidence that RotaTeq protects against these serotypes, but no evidence that it protects against G9. The second and perhaps overriding concern is that there are simply no data to show that either vaccine works in the poorest countries of Asia and Africa, where one child dies each minute from rotavirus infection. “We need to make testing in Africa and Asia a global priority,” says Glass. But even then, he cautions, “we won't have these studies for several years.” Experience with other live oral vaccines in poor countries provides reason for concern, says Glass. “We know when we put a live oral vaccine into the mouths of babes in poor countries, it is not processed the same way as in kids in Finland. We saw that with oral polio vaccine and cholera vaccine,” both of which require many more doses in, say, India or Africa, to induce the same immune response. And some earlier candidate rotavirus vaccines “were unsuccessful in African kids and less successful in Latin American kids.” This is where Wecker's RVP and other global health agencies are struggling to make a difference. Even before RVP was created with GAVI funding, a consortium of agencies, including CDC, the U.S. National Institutes of Health, WHO, the U.S. Agency for International Development, and the Children's Vaccine Fund, had been helping implement efficacy trials for Africa and Asia. “They won't do it on their own,” says Godal of GAVI. In 2005, with support from RVP and others, GSK will conduct two trials in South Africa and Bangladesh. Merck is also exploring developing country trials with RVP, GAVI, the Pan American Health Organization (PAHO), and others agencies. Paying customers first Sometime next year, results from the large clinical trials should be released. Then comes the tough challenge of getting the vaccines approved and, eventually, to the countries that need them most. Both GSK and Merck plan to recoup their investments by charging more for the vaccine in wealthy countries while negotiating a guaranteed supply and lower price for government purchase in poorer countries. Just how low is key, says Jon Andrus of PAHO, who notes that Latin American countries now struggle to pay$3.86 a dose for a combination childhood vaccine.

GSK has decided not to gamble on the U.S. market—at least for now. Instead, it is taking the unusual route of launching the vaccine first in Mexico—which has approved the vaccine even before clinical trials are complete—and then across Latin America. “We are doing the reverse of what's been done in the past,” said Jean Stephenne, president and general manager of GSK Biologicals, at a press conference in Mexico. “We are going where the need is greatest. … In Latin America we can save thousands of lives; in the United States we won't.”

GSK is also starting in a middle-income country with a substantial private market to support a two-tiered price for the vaccine. So far, Stephenne is mum on the price, saying only that it will be “not unreachable” and will be based on country income.

This new model is not problem-free, however. For one, Mexico's decision to license GSK's drug based on preliminary data has raised eyebrows among vaccine experts. “It sets a bad precedent,” says one. Although GSK hopes Mexico's example will speed approval across Latin America, Wecker questions whether Mexico's decision will carry the same weight as a formal blessing from the U.S. Food and Drug Administration (FDA).

Stephenne isn't ruling out the U.S. market, but, he concedes, liability is a key factor. “If by unluck there is one case of intussusception, we will have to prove it is not linked to the vaccine—that is a risk we didn't want to take.” In 2005, GSK will apply for approval in Europe, he said. And then, after discussions with FDA, the company will decide whether to apply in the United States, perhaps in 2010.

Merck, by contrast, is taking a more traditional route, testing extensively in the United States and Europe and seeking approval there in the second half of 2005. As Heaton explained, because the risk of intussusception was unknown, the company wanted to test the vaccine first in countries with high standards of medical care, should a problem arise. An added benefit, she says, is that FDA approval speeds acceptance globally. Heaton and others at Merck say the company is committed to introducing the vaccine into developing countries as soon as possible.

Both companies are counting on partnerships with GAVI and other public health agencies to pull it off. PAHO, for instance, will play a key role in introducing the vaccines into Latin American countries that can't afford to pay the same price as private patients in Mexico. Once all the safety data are in, an independent advisory board to PAHO will evaluate both vaccines. If the organization recommends that countries include rotavirus vaccine as part of routine immunization, it will then negotiate a uniform and affordable price for public health programs across the continent, says Andrus.

Similarly, once the vaccines have been approved, in perhaps 5 to 7 years, then WHO could make a global recommendation in favor of rotavirus vaccines. GAVI would then support the vaccine's introduction “in all the poorest countries where it makes epidemiological sense,” says Godal. GAVI is already working with both GSK and Merck to set a price for the 75 poorest countries of the world. What's an acceptable price? “All I can say is $10 for a set of immunizations is too much,” says Godal. “No price is affordable in Africa,” adds Wecker. If the companies and donors can find a way to make this new model work for rotavirus vaccines, which have the benefit of being relatively well understood and tested, then perhaps it can also speed the delivery of vaccines against tuberculosis, malaria, and AIDS. If the model doesn't pan out for rotavirus, however, poor countries may be waiting a long time before those newer vaccines arrive. • *6th International Rotavirus Symposium, 7–9 July 2004. 10. PALEONTOLOGY China Clamps Down on Mining to Preserve Cambrian Site 1. Dennis Normile, 2. Xiong Lei* 1. Xiong Lei writes for China Features in Beijing. Strip-mining for phosphate imperils Chengjiang, a vast and remarkably rich site of early Cambrian fossils The Chengjiang region of China's southwestern Yunnan Province has been a boon for scientists trying to understand the Cambrian explosion of life forms of some 500 million years ago. One key finding, a 3- centimeter-long fish, pushed back the first appearance of vertebrates by an astounding 55 million years. Another prized trophy, an invertebrate named Yunnanozoon, may be the oldest example of a chordate, the group that gave rise to vertebrates, although other scientists argue that Yunnanozoon could be part of an even more primitive group. Unfortunately for scientists, however, the discovery of this vast bed of well-preserved, soft-bodied fossils coincided with the discovery of valuable phosphate laced throughout the site. The resulting strip-mining has been a boon for the economy of one of China's poorest provinces. And it has created tension between two groups wanting to dig for different resources in the same area. Scientists scored a decisive victory recently when the Yunnan provincial government ordered the last of a number of major strip-mining operations around the Mount Maotian fossil site to cease operations by 1 October. Unfortunately, the closures come too late to prevent the Mount Maotian site from being left as an island of preservation amid a sea of environmental destruction—an important criterion when seeking the type of designation from international preservation organizations that China covets to attract tourists. And it does nothing to control mining around other fossil sites within the vast Chengjiang formation in other jurisdictions. “It makes my heart bleed,” says Hou Xianguang, a paleontologist at Yunnan University in Kunming, who is credited with finding the first Chengjiang fossils at Mount Maotian in 1984. Hou and his colleagues hope that protection will be extended to other sites, allowing scientists to continue to pursue hot topics such as the origin of vertebrates and the evolutionary relationships of marine animals. The Cambrian explosion began some 540 million years ago, when a multitude of new life forms bearing the body plans of most modern animals first arose. Some 10 million years later, what is now the Chengjiang formation was the bed of a vast shallow sea, and the bodies of these diverse new marine creatures were entombed in the sediment. Subsequent geologic movements pushed the formation above sea level and formed an arid, sparsely vegetated region of rolling hills while also forming pockets of phosphate ore. Ironically, these two treasures were discovered at about the same time. “When I was there in 1984 they had just begun surveying the potential [phosphate] reserves,” Hou recalls, and digging for both fossils and phosphate has accelerated ever since. The Chengjiang formation stretches over some 10,000 square kilometers. Hou says three groups are currently working three sites separated by up to 50 kilometers, and several more fossil-laden sites are yet to be explored. The fossils turning up are “fantastically interesting and important,” says Simon Conway Morris, a paleontologist at Cambridge University in the United Kingdom. And the Chengjiang formation is older than any other Cambrian-era fossil site yet discovered, giving insights into the earliest appearances of these new life forms. “In terms of the scientific problems of the Cambrian explosion, [the Chengjiang fossils] are extraordinarily interesting,” Conway Morris says. In 1999, Conway Morris and colleague Shu Degan of Northwest University in Xi'an reported the oldest vertebrate yet found, a 3-cm fish some 530 million years old. And Conway Morris believes more exciting finds are on the way. “People are really just scratching the surface at the moment,” he says. Mining operations have grown at a similar pace, and phosphate mining and processing provide roughly two-thirds of the annual tax revenues of Chengjiang County, which includes the Mount Maotian site. Dozens of enterprises have licenses to strip-mine specific tracts. And although the Chengjiang formation is vast and the mining is limited to certain regions, scientists worry that companies are encroaching on known fossil beds and disrupting others yet to be found. The problem is acute in the Mount Maotian area, where Chen Junyuan, a paleontologist who heads the Chengjiang work station of the Nanjing Institute of Geology and Paleontology (NIGP), says, “the digging is now just tens of meters away” from the spot where the first Chengjiang fossils were found. Officials of the De'an Phosphate Chemical Co., the mining operator, declined interview requests. Government officials have made some progress in protecting the Chengjiang fossils. An 18-square-kilometer tract around the Mount Maotian site and NIGP's nearby field station was one of the first 11 National Geological Parks designated by the Ministry of Land and Resources in 2001. But protection only extends to the park border. Li Minglu, an official in charge of environmental protection at the Ministry of Land and Resources, says the ministry can't intervene unless the mining crosses into the park itself. That stance doesn't satisfy Hou. “What sort of a park is it if it is surrounded and nibbled at by mining explosions, garbage, and smoking factories?” he asks. He would like to see mining controlled and kept away from known fossil sites. NIGP's Chen says the local government was at first reluctant to do anything about the mining because of its importance to the local economy. But local authorities had a change of heart when they decided to promote tourism by raising international recognition of the importance of Mount Maotian. One part of the plan to protect it would be a listing as a United Nations Educational, Scientific, and Cultural Organization (UNESCO) World Heritage Site. Chen Jiayou, manager of the county's Administration of the Chengjiang Fossils, says the province, Yuxi City, and the county are cooperating and have already spent about$2.5 million preparing their bid.

The next step is to gain the support of national officials, because applications to UNESCO must come from national governments. Meanwhile, Chen says they recognize that success will ultimately depend not only on the significance and protection of the site itself but also on having a well- preserved natural buffer zone around it. That would require an end to strip-mining.

Guo Yongming, an official working with the mining administration section of Yuxi City, says some of the operators had valid licenses to mine that were issued before the importance of the fossils was recognized. Before any mines could be closed, Guo says, “we had to agree on compensation.” Some 25 mines were closed over the last several years, including two in the vicinity of Mount Maotian. The government has spent \$7.5 million on legal expenses and compensation for mine operators with valid licenses. The one remaining mine in the Mount Maotian area had been scheduled to cease operations by the end of October, but the provincial government has moved up the date to 1 October.

Hou welcomes the move but wishes it had come sooner. Recognizing that time was running out, the mine operators have been trying to maximize output. “The mining has been very aggressive over the last 3 years,” Hou says.

Meanwhile, mining activities continue as usual in other parts of the region, including near the Haikou area where Hou's team and a group from Northwest University are currently digging. Hou doubts that the local Kunming city government will move to control the mining anytime soon. “They are not trying to boost tourism,” he says. Even so, he hopes local officials will eventually curtail mining operations before the shovels come too close to his precious fossils.

11. BIOENGINEERING

Biology and the Inkjets

1. Joe Alper*
1. Joe Alper is a writer in Louisville, Colorado.

Tissue engineers and other biologists experiment with cheap inkjet printers

Don't throw away that out-of-date inkjet printer. Older model inkjets, although lacking in the newest bells and whistles, are finding second lives as inexpensive robots that can dependably dispense minuscule amounts of growth factors and other proteins and even whole cells, in any pattern, gradient, or grid that can be drawn. Whether it's enabling a few thousand crystallization experiments, depositing gradients of attractants and repellants to study how growing nerve cells respond, or creating a grid of mammalian cells for high-throughput screening, that printer gathering dust could be just the tool for the creative biologist.

Inkjets can print repeatedly over a given area, offering the ability to create three-dimensional constructs simply and reproducibly. Older versions from the mid-1990s, which tend to have wider nozzles than newer ones, are particularly good at spitting out molecules and cells. For example, tissue engineers interested in studying cell interactions or creating artificial skin, blood vessels, and whole organs, are using inkjets to deposit precisely ordered layers of different cell types, complete with growth factors and extracellular matrices. In a prototype experiment published recently in the January 2005 issue of Biomaterials, bioengineer Thomas Boland of Clemson University in South Carolina and his colleagues have used a modified Hewlett-Packard (HP) inkjet to apply viable mammalian cells to a variety of “papers,” including collagen gel. The Clemson team has also printed sheets of skin cells that could be used in skin grafting.

Although inkjet technology has already found widespread use in a variety of nonpublishing applications, such as microelectronics manufacturing, its potential in cell and molecular biology research is only now coming into focus. “This is a very cool use of inexpensive technology,” says Jeffrey Esko, a molecular biologist at the University of California, San Diego.

Esko, who in the mid-1970s invented the widely adopted replica-plating technique for making copies of mammalian cells growing in petri dishes, says that inkjet printing could have an equally huge impact on biology. “Using any one of a number of cell lines, you could screen an entire genome for mutations on a single piece of paper or study how different growth signals affect the possible differentiation pathways of stem cells,” he explains. “Inkjet printing really opens up the possibility of doing some amazingly complex experiments that have been out of our reach until now.”

Inkjet technology has entered the biology lab because of its ability to generate, under surprisingly benign conditions, tiny droplets of reproducible size and deposit them at a spot with positional accuracy of 100 micrometers or better. Each printer comes with its own software program, known as a printer driver, that translates computer-generated graphical information into a specific pattern of droplets.

Depending on the brand, inkjets use one of two technologies. HP printers heat the material in the ink cartridges to create a meniscus, which pinches off to form a droplet. Although many biologists initially assumed that the heat needed to generate the droplet would damage proteins and cells, Boland found that the internal temperature of a droplet rises a mere 10°C. “Proteins and cells come through just fine,” he says. Epson and Canon printers use acoustic energy, rather than heat, to generate the meniscus. An advantage of this approach is that it is possible to create much smaller drops—of a picoliter or less—by proper tuning of the acoustic frequency.

To study how muscle cells respond to multiple cues, Ryoichi Matsuda and colleagues at the University of Tokyo have employed a Canon inkjet to create arrays of various growth factors. In one recent study, the researchers deposited 16 different combinations of two growth factors onto a polystyrene sheet and documented the growth of muscle cells placed at each site. Although the data, published last year in Zoological Research, revealed no surprises, the experiment did demonstrate how easy it is to design and analyze a cell's response to multiple, simultaneous signals, Esko says.

To lay down mammalian cells, along with growth factors and immobilizing matrices, in layers, a step toward what Boland calls “organ printing,” he and his colleagues are using a basic HP printer modified so that the printing substrate can pass straight through the printer without curling around a roller. They also rewrote the printer driver to adjust for the fact that the viscosity of biological materials, which affects droplet size, is not uniform. “We want to try printing multiple cell types in a three-dimensional matrix to see if we can mimic the structure of a tissue and to see if the cells will grow in the right orientation to one another,” Boland explains. His group is attempting to deposit nerve and muscle cells next to one another to see if they form functional neuromuscular junctions.

Other investigators are making more significant modifications to their printer. Raul Cachau, a chemist at the National Cancer Institute in Frederick, Maryland, and Eduardo Howard of Argentina's Instituto de Fisica de Liquidos y Sistemas Biologicos have tuned the acoustic energy generator on an Epson printer to create picoliter-size droplets for crystallographic studies. “When you have a few micrograms of some novel compound, it's hard to determine the optimal conditions for growing crystals,” he says. “But with the inkjet printer you can conduct hundreds of experiments … with minuscule amounts of compound.”

Cachau's goal is to develop the technology so that labs, particularly those in less developed countries, can build their own instrument for a few hundred dollars. Of course, as anyone who owns an inkjet printer can attest, the printer is cheap. It's the ink that's expensive.

12. CLIMATE CHANGE

A Bit of Icy Antarctica Is Sliding Toward the Sea

1. Richard A. Kerr

The latest gauging of West Antarctic glaciers confirms that when the ocean eats at one end of a glacier, it can draw far-distant ice toward the sea, with potentially dangerous consequences

As the global climate warms up, glaciologists' big worry is polar ice, especially the ice sheet of West Antarctica, the muscular arm that juts from the huge mound of ice in East Antarctica. They aren't concerned about warmer air per se; even the thinner West Antarctic Ice Sheet (WAIS) would hold out against its effects for millennia. But researchers have long wondered whether warming could somehow get at the WAIS indirectly, destabilize it, and send its ice into the sea to melt, raising sea level up to a disastrous 5 meters in a few centuries. With the publication online (www.sciencemag.org/cgi/content/abstract/1099650) of the latest survey of glaciers flowing into West Antarctica's Amundsen Sea, most glaciologists now allow that there probably is a way for warming to accelerate the movement of at least some of the WAIS ice toward the sea.

Glaciologist Robert Thomas of NASA contractor EG&G at the Wallops Island facility in Virginia and colleagues confirm that the half-dozen glaciers flowing into the Amundsen Sea have been getting thinner and thinner the past 15 years, and that one of them—the Pine Island Glacier—has been flowing faster and faster for more than 100 kilometers inland. “It's not necessarily a sign of [WAIS] collapse,” says glaciologist Richard Alley of Pennsylvania State University, University Park, “but it could lead to a collapse.”

However, no one can say whether the recent glacial acceleration will continue, whether it could reach more distant ice if it does continue, or whether other, more voluminous parts of the WAIS could suffer similar effects. “We're not running for the hills,” says Alley, but “this is the wake-up call for the scientific community to get serious about it all.”

Since the start of the 1990s, glaciologists have been closely monitoring the flow of ice from the Pine Island Glacier and nearby glaciers using motion-sensing radar, ice- penetrating radar, and laser and radar altimeters mounted on satellites and aircraft. By the end of the decade, the ice in at least some glacial channels nearing the sea seemed to be thinning and accelerating.

To learn more, Thomas and his colleagues, in cooperation with Centro de Estudios Científicos in Valdivia, Chile, rode an instrument-laden Chilean Navy P-3 aircraft 2700 kilometers to the remote Amundsen Sea coast. The onboard ice-penetrating radar found that the ice is far thicker than thought, on average 400 meters deeper than previously estimated near the coast. Combined with satellite radar velocity estimates from the late 1990s, those greater thicknesses implied that the glaciers are hauling away about 253 cubic kilometers of ice per year. That's about 90 cubic kilometers more than accumulates each year from snowfall.

By analyzing recent satellite radar data, Thomas and colleagues confirm that ice withdrawals have been accelerating, at least through the Pine Island Glacier, the largest of the group. They calculate that it sped up by 3.5% between April 2001 and early 2003, making for a 25% increase since the mid-1970s. And the drawdown is not limited to areas near the coast. The P-3 data show a thinning, presumably induced by the faster flow, that extends along the main trunk of the Pine Island Glacier and averages about 1.2 meters per year between 100 and 300 kilometers inland.

These latest results from West Antarctica confirm an unsettling view of glacier behavior. For 30 years, glaciologists have debated whether one part of a glacier can “feel” what's happening in a distant part of the same glacier. At the coastal end of the Pine Island Glacier, for example, warmer water seems to be melting the underside of the glacier's floating ice shelf (Science, 24 July 1998, pp. 499 and 549), pushing landward the point at which the advancing glacier floats off the sea floor.

If an ice shelf pinned against an embayment's shore and floor helps slow a glacier's flow—as was hypothesized in the 1970s—and if changes at the coast could make themselves felt far up the glacier, then the Pine Island Glacier's so-called grounding line retreat would accelerate glacier flow well upstream. The researchers think that's what they're seeing. “I'm convinced the glacier feels what is happening a long way away,” says Thomas. Similar accelerations struck after two other floating ice tongues recently broke up in West Antarctica and Greenland (Science, 30 August 2002, p. 1494).

“It's a very impressive piece of work,” says Alley. “Too many different lines of evidence are agreeing now” for them to be wrong about the thinning or the speedup of the past 10 to 15 years. “Ice shelves may well play a role in the dynamics of glaciers,” agrees geoscientist Michael Oppenheimer of Princeton University in New Jersey. But the next problem is that “we don't know why things are melting away at Pine Island Glacier.” Oceanographers can't say whether the ocean warming that seems responsible is part of a cycle that will reverse itself or a long-term trend driven by greenhouse warming. And they can't say whether the WAIS's two largest ice shelves—the Texas-size Ronne and Ross ice shelves—could be melted as well.

Even if glaciologists knew what the ocean was going to do, their models for predicting glacier behavior are still so rudimentary that they can't say whether more distant, slower moving ice feeding the main ice streams will respond too. So plenty of uncertainties remain, notes Oppenheimer, but he adds, “I'm starting to get worried.”

13. AAS HIGH ENERGY ASTROPHYSICS DIVISION MEETING

Reconstructing a Star's Demise, Bit by Exploded Bit

1. Robert Irion

NEW ORLEANS, LOUISIANA—The energetic universe jazzed 440 scientists here from 7 to 11 September at the American Astronomical Society's High Energy Astrophysics Division meeting.

The death of a giant star is both glorious and messy. A supernova sprays freshly forged elements into space in an inside-out radioactive jumble, while shock waves reverberate through the expanding storm of matter. The entire hot cloud glows in radio waves, optical light, and x-rays. Now, the most exquisite x-ray view yet of a supernova's remains has fired up astrophysicists who yearn to retrace the explosion—a process still shrouded in mystery.

The debris forms a well-known object just 10,000 light-years away called Cassiopeia A, first spotted in the late 17th century. As the youngest and brightest supernova remnant, “Cas A” is a natural target for x-ray satellites. Earlier this year, NASA's Chandra X-ray Observatory stared at Cas A for 11.5 days. The detailed maps thrilled astrophysicists at the meeting. “We won't have another image with this resolution for some time,” says Una Hwang of NASA's Goddard Space Flight Center (GSFC) in Greenbelt, Maryland.

Chandra's sharp vision exposed the outermost blobs of expelled matter, still racing at nearly 10,000 kilometers per second. On opposite sides of the remnant, the silicon-rich blobs form two prominent jets, one of which was barely seen in previous images. Such double-sided jets—junior versions of the ones thought to blast outward from gamma ray bursts—may arise more commonly than expected in ordinary supernovas, Hwang says.

In some supernova models, outflows of matter escape into nearby cavities of mostly empty space. But faint knots at the tip of one jet in Cas A are so hot that they clearly are blasting through denser material around the original star, says astrophysicist J. Martin Laming of the Naval Research Laboratory in Washington, D.C. “This really clinches the observation of a reverse shock wave [from the pressure of the surrounding medium] heating the jets,” he notes. That more violent physical picture will lead to a firmer calculation of how much energy the star channeled along those directions.

Chandra's image of a bright dot within Cas A—presumably a neutron star formed when the star's core collapsed—shows that the object is darting away from the remnant's center at 330 kilometers per second. Although the speed isn't unusual, the direction is strange. “We'd expect the kick to be aligned with the jets, but it's perpendicular to them,” Hwang says. “It's a bit of a puzzle.” This and other aspects of the explosion's dynamics will open “a window on neutron star birth,” comments astrophysicist David Helfand of Columbia University in New York City.

Fully re-creating the star's immolation from the Chandra data—and images at other wavelengths—will take years. But it's a worthy goal, researchers say, because the elements of our world came from such explosions long ago. “This is a tremendously exciting data set,” says astrophysicist Michael Stage of the Massachusetts Institute of Technology (MIT) in Cambridge, noting that x-ray spectral patterns reveal the elemental mixture of each burning knot of gas. “For the first time, we have enough x-ray counts to get really good spectra in regions where substantially different physics is going on.”

14. AAS HIGH ENERGY ASTROPHYSICS DIVISION MEETING

X-ray Flares Size Up a Neutron Star

1. Robert Irion

NEW ORLEANS, LOUISIANA—The energetic universe jazzed 440 scientists here from 7 to 11 September at the American Astronomical Society's High Energy Astrophysics Division meeting.

The densest stuff in the universe—matter just shy of vanishing into a black hole—inhabits the weird interiors of neutron stars. Created at the hearts of supernovas, these objects crush more than a sun's worth of mass into balls just 20 kilometers wide or so. But that “or so” vexes scientists. Knowing the exact size of a neutron star is critical to determining whether its core consists merely of neutrons crammed together or something more exotic, such as hypothesized “strange quark matter.”

New results announced at the meeting narrow the possible diameters for one neutron star halfway across the Milky Way: 19 to 30 kilometers, with a most likely value of 23 kilometers. That range doesn't yet allow theorists to eliminate any models for ultradense matter, but it shows that earlier, disputed measurements were probably on track. “There are uncertainties, but this one piece of information is terribly useful,” says astrophysicist Madappa Prakash of Stony Brook University in New York.

To derive their estimate, graduate student Adam Villarreal of the University of Arizona, Tucson, and NASA GSFC astrophysicist Tod Strohmayer examined light from a neutron star that sucks gas from a companion. Hydrogen and helium pile into a thickening blanket on the spinning star. Every few hours, the layer's pressure and temperature soar high enough to ignite a fierce thermonuclear burst.

NASA's Rossi X-ray Timing Explorer satellite detected 38 such bursts from the binary during sporadic observations over 7 years. When Villarreal and Strohmayer combined all burst records into a single statistical analysis, they concluded that x-rays from the flares flicker 45 times every second. The neutron star must spin at that rate, they deduced—a surprise, because other neutron stars in similar binaries spin at least four times as fast.

The slow spin vindicates a 2002 study of the strength of gravity on the same body, says astrophysicist Deepto Chakrabarty of MIT. That research—which led to a wider range of plausible masses and sizes—came under fire, because skeptics claimed a rapid spin would skew the results. With the slower rotation pointing to a reliable gravity figure, Strohmayer and Villarreal factored the spin rate into a model of how the star radiates in x-rays. The best fit was a diameter of 23 kilometers and a mass about 1.75 times as massive as our sun, they reported—a slightly heftier mass than that measured for most other neutron stars.

Theorists praise the technique, but they caution that interpreting the results is fraught with potential errors. “This inference stems from much of the [burst] activity taking place exactly on the surface, but it could happen at various levels of depth,” says Prakash. His colleague at Stony Brook, astrophysicist James Lattimer, adds that observers must identify the unmistakable fingerprints of a broader suite of elements in the x-ray flares to tighten gravity calculations.

“We need to know the radius within a kilometer to exclude models [of neutron star matter],” Lattimer says. For now, a strange stew of squeezed quarks—which would produce a smaller neutron star, in most cases—remains viable.

15. AAS HIGH ENERGY ASTROPHYSICS DIVISION MEETING

A Positron Map of the Sky

1. Robert Irion

NEW ORLEANS, LOUISIANA—The energetic universe jazzed 440 scientists here from 7 to 11 September at the American Astronomical Society's High Energy Astrophysics Division meeting.

Astronomers have produced a startling new sky survey, based not on matter that shines but on antimatter that annihilates. The sources of the particles aren't yet known, but a European-led team reported that the antimatter clusters around the home of the Milky Way's most ancient stars.

For 30 years, astronomers have known that our galaxy creates a steady flow of positrons, the antimatter counterparts of electrons. When a positron and an electron collide in space, they destroy each other and spit out two gamma rays. The European Space Agency's INTEGRAL satellite, launched in October 2002, records those sparks far more sensitively than previous missions had done (Science, 19 December 2003, p. 2051).

The satellite's first all-sky map of the emission, released at the meeting, shows a bright patch of gamma rays overlying the galaxy's central bulge of old stars. None of the energy that was detected streams from the flat disk, where younger stars like our sun reside. “Young stars appear ruled out,” says astrophysicist Georg Weidenspointner of the Centre d'Etude Spatiale des Rayonnements in Toulouse, France. “We did not expect [the central concentration] to this extent.”

That leaves two classes of sources, Weidenspointner says. Old stars in binary tangos with white dwarfs, neutron stars, or black holes can flare up in various explosions including type 1a supernovas—the same objects used to trace the accelerating growth of the universe. Such supernovas spawn huge amounts of unstable nickel-56, which emits positrons during its decay chain. That's an ongoing bounty, says NASA GSFC astrophysicist Bonnard Teegarden: “You get one of these every few hundred years, producing a bunch of positrons, and it takes them 100,000 years to 1,000,000 years to annihilate.”

Eager theorists are pursuing a more speculative source: lightweight particles of dark matter that may decay within a cocoon around the galaxy's core. As INTEGRAL watches the sky, it might be able to distinguish between a diffuse antimatter glow from widespread dark matter and more pointlike sources from old stars. However, a new study led by astrophysicist John Beacom of Ohio State University in Columbus argues that dark matter is a long shot. The patterns of extra radiation expected from such events don't match the energies seen by earlier gamma ray satellites, Beacom's team claims (arxiv.org/abs/astro-ph/0409403).

INTEGRAL's detections will increase sixfold as the mission goes on, so the fuzzy positron map will only get sharper. As astrophysicist Dieter Hartmann of Clemson University in South Carolina says, “They are really well on their way to conducting positron astrophysics.”

16. AAS HIGH ENERGY ASTROPHYSICS DIVISION MEETING

Snapshots From the Meeting

1. Robert Irion

NEW ORLEANS, LOUISIANA—The energetic universe jazzed 440 scientists here from 7 to 11 September at the American Astronomical Society's High Energy Astrophysics Division meeting.

Orbits of doom. Astronomers may have caught their first glimpse of a blob of matter spiraling toward a giant black hole. X-rays from the core of a galaxy cycled in a repetitive pattern nearly four times during a daylong view by Europe's XMM-Newton satellite. A team led by Kazushi Iwasawa of the University of Cambridge, U.K., concluded that a hot spot within an accretion disk—a flattened torus of gas that envelops the black hole—orbited at one-fifth the speed of light, at about the same distance from the hole as Earth's distance from the sun. Colleagues were tantalized, but some warned that the signals aren't statistically compelling.

Cold search. Neutrino sensors embedded in the Antarctic ice have not yet traced any of the zippy particles to a specific source. Analysis of 3369 neutrinos detected by the AMANDA experiment through 2003 showed that they came from random directions, reported astrophysicist Steven Barwick of the University of California, Irvine. The new study—three times as sensitive as the one reported in the team's most recent publication—included attempts to pinpoint neutrinos from 119 gamma ray bursts. “AMANDA is just too small,” Barwick said. A gigantic successor, called IceCube, will spot far more neutrinos starting next year.

Pulsar power. Hundreds of radio pulsars—the spinning remnants of massive stars that explode—probably swarm around the black hole at our Milky Way's core. Radio telescopes should find several pulsars with orbits lasting less than a century, predicted astrophysicist Eric Pfahl of the University of Virginia, Charlottesville. Pfahl reported that subtle variations in the clockwork blips from such pulsars would effectively map the black hole's turbulent environment. Searches are under way at the Green Bank Telescope in West Virginia and elsewhere.

17. 2004 VISUALIZATION CHALLENGE

Photography

1. David Grimm

WINNER: Autofluorescence of Tick Nymph on a Mammalian Host

Marna E. Ericson, University of Minnesota, Dermatology

A blood-sucking tick has never looked so stunning. The makeover is thanks to Marna Ericson of the University of Minnesota, Minneapolis, who used laser scanning confocal microscopy to capture the autofluorescence of a common deer tick as it feasted on the ear of a golden hamster.

When ticks feed, they transmit bacteria to their hosts that can cause a variety of illnesses in humans, including Lyme disease. Ericson's group wanted to understand how this transmission takes place by engineering fluorescent versions of the tick-associated bacteria. But first the researchers needed to make sure that the color they selected for the bacteria would be distinguishable from the natural autofluorescence of the tick and hamster.

Judging by the rainbow of hues in Ericson's photograph, this could be a challenge. The colors of the tick's mouth range from the emerald green and brilliant violet of its outer shell to the volcanic red and salmon-orange of its flesh-piercing structures. Even the tissue of the hamster's ear fluoresces; that's the faint olive glow of the background. Ericson says the photograph highlights the “importance of good [autoflourescence] controls.”

“I found this picture incredibly striking,” says panel of judges member Felice Frankel. Frankel believes the picture won because of its “clarity of representation and the way it captures a real-time moment.”

18. 2004 VISUALIZATION CHALLENGE

Illustration

1. David Grimm

WINNER: Water Permeation Through Aquaporins Emad Tajkhorshid and Klaus Schulten, Theoretical and Computational Biophysics Group, University of Illinois, Urbana-Champaign

Aquaporin channels provide a conduit for water to cross the cell membrane, but they somehow prevent smaller particles, like protons, from getting through. To understand this selectivity, computational biophysicists Emad Tajkhorshid and Klaus Schulten of the University of Illinois, Urbana- Champaign, constructed one of the largest atomic simulations ever attempted. The group assembled four membrane-bound aquaporin channels from more than 55,000 digital atoms and then added virtual water.

The winning illustration is a snapshot of the simulation in progress. Boomerang-shaped water molecules flip as they march single file through the narrow pore of the gold aquaporin, while the red balls and fibers that make up the cell's membrane keep the outside water (top) from mixing with the cellular pool (bottom). The display allowed the researchers to crack the mystery of aquaporin's discriminating tastes. “The flipping of the water molecules prevents protons from hopping through the pore,” says Tajkhorshid, who notes that this novel mechanism of selectivity could not have been determined using traditional experimental methods.

“This is an almost-perfect use of existing [protein-modeling] software,” says panel of judges member Felice Frankel. “It intelligently combines many of the methods used to represent proteins while successfully expressing a larger scientific idea.” Plus, she says, “it's also very beautiful.”

HONORABLE MENTION: Spiral IV

If you could climb the twisted ladder of a DNA molecule and look down, you might see something like the image above. Kenneth Eward, a science artist at BioGrafx Scientific & Medical Images in Ovid, Michigan, used x-ray crystallographic data from DNA molecules to paint a unique portrait of the double helix. The image omits the chemical bonds that crisscross the center of the molecule, so that the structural features of the helix can be seen more easily.

19. 2004 VISUALIZATION CHALLENGE

Informational Graphics

1. David Grimm

WINNER: Mount Etna

David Fierstein,

David Fierstein Illustration,

Santa Cruz, California

Science illustrator David Fierstein cuts to the core of one of the world's most unusual volcanoes in his illustration of Mount Etna. The image merges the latest scientific data with state-of-the-art 3D modeling software to give a comprehensive view of the volcano's rich and violent history.

Located on the east coast of Sicily, Mount Etna is Europe's largest volcano and one of the most productive in the world. Eruptions in the past 3 years alone have destroyed tourist complexes and threatened nearby towns. New evidence suggests that Mount Etna is growing increasingly violent and may someday rival Mount St. Helens and Pinatubo in ferocity.

Fierstein's graphic documents the changing nature of the volcano by combining this new evidence with prior research. The insets at the upper left illustrate how the unique geological location of the volcano allows it to produce large volumes of magma, and the panel at the lower right provides details about recent lava flows and eruptions. The central image chronicles the evolution of Mount Etna from a relatively flat shield volcano to the mountainous cone that looms over the countryside today. Fierstein says the large, glowing magma pools in this image are the most salient part of the graphic, in that they highlight Mount Etna's hypothesized “dual plumbing system,” which may give clues to the volcano's future activity.

“This image is a great example of how to illustrate a complex set of relationships,” says panel of judges member Thomas Lucas. Fellow panelist Boyce Rensberger agrees: “It shows you everything you'd want to know,” he says, “except, perhaps, for the people screaming down below.”

20. 2004 VISUALIZATION CHALLENGE

Multimedia--Interactive

1. David Grimm
21. 2004 VISUALIZATION CHALLENGE

Multimedia--Noninteractive

1. David Grimm

WINNER: Bat Intercepts Flying Insect

Cynthia F. Moss and Kaushik Ghose,

University of Maryland,

College Park

Under infrared light, a large, winged object locks onto and overtakes a small blip while a radarlike display tracks the entire proceeding. This isn't a military exercise; it's an experiment designed to understand how bats use sonar to capture their prey.

Bats emit high-frequency sounds when hunting and navigating, but no one knew how they aimed these sonar beams until neuroethologist Cynthia Moss and graduate student Kaushik Ghose created a bat cave in their laboratory at the University of Maryland, College Park. The researchers padded a large room with acoustic foam and set up two high-speed infrared cameras and 16 strategically placed microphones. Then they introduced a large brown bat and a praying mantis.

The drama unfolds in a two-frame multimedia presentation. In the left frame, a slowed-down movie captures the visual action, complete with bat chirps and a crunch when the mantis meets its fate. On the right, an animated diagram traces the hunt from above and incorporates the microphone data to pinpoint the direction of the bat's sonar (represented by the darker bars on the gray-scale cone). The presentation reveals that a bat “locks its beam on a target” when hunting, says Ghose, who notes that the behavior is akin to baseball players keeping their eye on the ball.

“This is a unique visualization of an amazing event,” says panel of judges member Thomas Lucas. He says the judges were impressed with the combination of video, sound, and sonar that puts the viewer in the bat's world. “This is something we never get to see,” says Lucas. “It always happens in the dark.”