# News this Week

Science  13 Mar 2009:
Vol. 323, Issue 5920, pp. 1412
1. BIOMEDICAL RESEARCH

# A First Step in Relaxing Restrictions on Stem Cell Research

1. Constance Holden

Scientists are breathing a huge sigh of relief now that President Barack Obama has put his signature on an executive order lifting the restrictions on stem cell research laid down by President George W. Bush on 9 August 2001.

In the same chandeliered White House room where 2 years ago Bush announced his veto of a bill passed by Congress to override his policy, Obama announced “we will lift the ban on federal funding for promising embryonic stem cell research [and] will vigorously support scientists who pursue this research.”

The signing ended with a standing ovation from the crowd, which included politicians, lobbyists, ethicists, stem cell researchers, and a goodly contingent of Nobelists—including Harold Varmus, head of the President's Council of Advisors on Science and Technology. Even Kyoto University researcher Shinya Yamanaka—famous for developing induced pluripotent stem (iPS) cells—flew in for the event. Also in evidence was Robert Klein, maestro of the California Institute for Regenerative Medicine.

Obama also used the occasion to tackle the alleged politicization of the science behind subjects ranging from stem cells to global warming during Bush's reign. The president announced that he has sent a memorandum to the Office of Science and Technology Policy directing it to develop “a strategy for restoring scientific integrity to government decision-making” within the next 120 days. Kurt Gottfried, chair of the Union of Concerned Scientists, says the memo signals “a sea change from the last Administration.”

The signing of the new executive order on human embryonic stem (hES) cells is “a great outcome,” says University of Pennsylvania stem cell researcher John Gearhart. It “lifts a cloud in many areas. … It will allow more people to get involved [in hES cell research]—and it also sends a message internationally that [National Institutes of Health (NIH)-funded researchers] can collaborate with people.” The development of iPS cells, ES-like pluripotent cells that can be grown without the destruction of embryos, has removed some of the intense pressure for scientists to have access to ES cells, and Gearhart himself is using iPS cells. Nonetheless, he says he still needs ES cells to study the mechanisms of embryogenesis and as a standard against which to compare iPS cells.

The executive order sweeps away a cumbersome level of bureaucracy that required researchers who receive both federal and private funds to keep separate accounting systems and use separate equipment depending on which cells they are working with. Harvard University researcher Kevin Eggan said earlier this year that the expected policy change “will have a huge immediate impact on my daily life.” Roughly half his graduate students have NIH training grants, which has meant they could not participate in any non-NIH-approved work. The change, he said, “will mean I don't have to spend 7 or 8 hours a week dealing with Harvard administration making sure that the costing allocations for my lab are appropriately followed.”

Some other scientists see the executive order's value as primarily symbolic. Because so many scientists are focusing on iPS cells, “I think it is going to have minimal effect in the short term” on research, says Martin Grumet, director of the Rutgers Stem Cell Research Center in Piscataway, New Jersey.

NIH has 120 days to finalize guidelines on research with the hundreds of hES cell lines that will soon be available to researchers. Such guidelines will likely draw heavily on existing ones on informed consent and other procedures that have been put out by the National Academy of Sciences and the International Society for Stem Cell Research. It's a “very exciting time at NIH right now,” says Story Landis, head of the NIH Stem Cell Task Force.

NIH Acting Principal Deputy Director Lawrence Tabak said at a press conference that “our expectation is [that] some stimulus money will be available for use with the new guidelines.” That's good news for researchers hoping for a piece of the package, which, among other things at NIH, allocates $200 million to a 2-year grants program that covers stem cells, regenerative medicine, and a dozen other fields. Congress is already poised to pass legislation to codify the new order. The White House has been working with members of both the House and the Senate to ensure swift passage of the measure that was twice vetoed by Bush. Those bills (S. 487 and H.R. 873) specify that federally funded researchers can work only with ES cell lines derived from embryos created for fertility treatment that would otherwise be discarded. Political battles are not yet over, however. Representative Chris Smith (R-NJ), co-chair of the House Pro-Life Caucus, held a press conference accusing the Administration of “incentivizing the creation and destruction of human embryos.” Francis Collins, former head of NIH's National Human Genome Research Institute, told Science he is trying to help members of the religious community come to terms with the policy. Federally funded scientists will still not be allowed to derive new lines of hES cells because of the 13-year-old Dickey-Wicker Amendment. Added annually to the health appropriations bill, the amendment prohibits federally funded researchers from harming human embryos. DeGette has indicated, however, that the time may be ripe to start asking legislators to reconsider their support for the measure. 2. RESEARCH FUNDING # England Spreads Its Funds Widely, Sparking Debate 1. Daniel Clery Competitions always produce winners and losers, along with appeals to the referee about perceived unfairness, but last week's announcement of how £1.57 billion in annual research funding will be distributed to English universities drew complaints from some unlikely sources: top research institutions. Science heavyweights, including Imperial College London, Cambridge University, and Southampton University, received cuts or below-inflation increases in their annual funding, and they're not happy about it, warning of possible layoffs. Nottingham University; Queen Mary, University of London; and others that won substantial increases are not complaining. Indeed, a large number of England's “new universities,” those created in the 1990s, are ecstatic, having earned money from this research pot for the first time. “This is a great encouragement,” says Les Ebdon, vice-chancellor of the University of Bedfordshire. Almost all of the U.K.'s universities are primarily state-funded, and to those conducting international-level research, the government allocates annual block grants to cover departmental overhead costs. But not every institution gets an equal share: The higher the quality of a university's research, the more it gets. Who gets what is decided by a competition held at irregular intervals called the Research Assessment Exercise (RAE), a huge peer-review process involving more than 1000 researchers serving on 15 subject panels and 67 subpanels. Two-thirds of the annual money is allocated according to the RAE results. English officials used the last RAE, carried out in 2001, to concentrate funding in departments doing top-level international research, leaving many with no funding despite doing good work. (Scottish, Welsh, and Northern Irish education officials also use RAE data but independently devise their allocation strategies.) The RAE in 2008 saw a slight change of methodology: Instead of giving a single quality score to whole departments, it noted what percentage of each department was doing work in each of four grades, from nationally recognized to world leading (Science, 2 January, p. 24). When the results were announced last December, the RAE revealed many “pockets of excellence” in institutions not normally lauded for their research, particularly those created after 1992 when a new law gave polytechnic colleges the right to become universities. In the allocations for England, revealed on 5 March, 25 institutions that previously received no RAE-allocated funding are now expecting a check in the mail, and others saw huge increases. The University of Lincoln, for example, sees its share of the research funding jump from £266,000 to £1.9 million. The new funding “will make it easier to hold on to world-class research teams,” says Ebdon. Changes in student demographics could have made the allocations even worse for England's traditional research universities. The number of university students in the United Kingdom has ballooned over the past decade, but most flocked to humanities and social science courses while the number enrolling in science has remained fairly steady. As a result, universities hired many more humanities and social science academics, who then won good ratings in the RAE. To prevent these newcomers draining money from science departments, the government decided that traditional science subjects would receive the same proportion of the whole pot as in previous years. “The ringfencing was absolutely crucial,” says Hilary Leevers of the Campaign for Science and Engineering. Nonetheless, there were some dramatic changes of fortune. Nottingham University will receive an extra £9.7 million in 2009–10, a 23.6% increase, while Imperial will get £5 million less, a 5.1% cut. The 16 English members of the Russell Group, which represents the United Kingdom's top research-intensive universities, together receive 3.3% more than last year. The whole fund being distributed was increased by 7.7%, however, indicating that England is spreading its research wealth more widely. That's a mistake, the traditional powerhouses warn. “Britain can't sustain 101 internationally competitive universities. If it's going to compete it's got to concentrate its resources,” says epidemiologist Roy Anderson, rector of Imperial College. 3. BIOMEDICAL RESEARCH # Humane Society Launches Offensive to Ban Invasive Chimp Research 1. Jon Cohen The Humane Society of the United States (HSUS) last week stepped up its long-running campaign to end biomedical research with chimpanzees, orchestrating the broadcast of an “exclusive” story by ABC News that sharply criticized a leading primate research center, filing a 108-page complaint against the facility, accusing the U.S. National Institutes of Health (NIH) of violating its own moratorium on breeding chimpanzees, and working with Congress to draft and introduce new legislation that would ban “invasive” research on great apes. HSUS's efforts quickly grabbed the attention of researchers as well as government agencies that support or oversee the well-being of the 1200 “research” chimpanzees in the country. On 4 March, HSUS revealed that for much of 2008, an unidentified employee at the New Iberia Research Center, part of the University of Louisiana (UL), Lafayette, worked undercover for HSUS and secretly videotaped the care and handling of some of the facility's 6000 monkeys and 350 chimpanzees. The video shows a chimpanzee falling from a perch and smacking the floor after being darted by a tranquilizer gun, an anesthetized monkey rolling off a table, a baby monkey writhing while receiving a feeding tube, and other strong images of caged primates. “A major issue for us is the psychological deprivation and torment that these animals are enduring,” said HSUS President Wayne Pacelle at a press conference. HSUS filed a complaint that day with the U.S. Department of Agriculture (USDA), alleging 338 “possible violations” of the Animal Welfare Act at New Iberia, one of four facilities in the United States that conducts biomedical research with chimpanzees. USDA Secretary Tom Vilsack immediately ordered a “thorough investigation.” In January, USDA had received a separate complaint of alleged violations at New Iberia from Stop Animal Exploitation NOW. A USDA investigation revealed no violations, nor did a routine USDA inspection in September 2008. HSUS also charged that the National Institute of Allergy and Infectious Diseases (NIAID) has violated NIH's own moratorium against breeding chimpanzees. The agency has had a$6.2 million contract with New Iberia to supply four to 12 infant chimpanzees each year between September 2002 and 2009 for research on several viral diseases.

On 5 March, Representative Edolphus Towns (D-NY) introduced the Great Ape Protection Act of 2009, which prohibits “invasive” research on great apes in the United States and federal support for such research anywhere. “Invasive” is defined as “any research that may cause death, bodily injury, pain, distress, fear, injury, or trauma.” This would include drug testing, as well as anesthetizing or tranquilizing animals. The bill has 22 cosponsors and has been referred to the House Committee on Energy and Commerce. Kathleen Conlee, director of program management at HSUS, said her group helped draft the bill and that Towns “agreed to introduce the legislation on a timetable we asked for.” Towns introduced a similar bill last year; it was referred to three committees but never moved forward.

UL Lafayette, NIH, and researchers who conduct invasive research on chimpanzees have challenged the HSUS media, regulatory, and legislative blitz on many fronts. UL Lafayette President E. Joseph Savoie said the images on the video “are based on interpretation and impression.” At a press conference, employees at New Iberia contended that many of the most disturbing images were distorted. For example, they alleged that the person who shot the undercover video of the monkey falling from a table was a technician responsible for the care of anesthetized animals who possibly could have tended to the monkey. Savoie contended that HSUS's allegations against New Iberia were calculated to help pass the new legislation.

NIH told Science that its contract with New Iberia for the supply of infant chimpanzees does not violate its moratorium on breeding the animals. That moratorium applies only to chimpanzees owned or supported by NIH's National Center for Research Resources, which in 1995 abandoned a large chimpanzee-breeding program for fiscal reasons (Science, 26 January 2007, p. 450). “The moratorium was not intended for privately owned chimpanzees, or to apply to the other NIH Institutes,” an NIH statement read, further noting that NIAID does not directly pay for breeding of the infant chimps, which are returned to New Iberia for long-term care. John McGowan, deputy director of science management at NIAID, says researchers there who study respiratory syncytial virus and different hepatitis viruses need infant chimps because they have not been exposed to these pathogens. He adds that they have also been used in biodefense studies related to smallpox and anthrax but that the animals were not harmed.

Several researchers who conduct studies on chimpanzees say the legislation is shortsighted. Geneticist John VandeBerg, the chief scientific officer at the Southwest Foundation for Biomedical Research in San Antonio, Texas, says researchers there use chimpanzees primarily for testing drugs and vaccines against hepatitis B and C, diseases that he notes affect nearly 500 million humans.

Neuroscientist Todd Preuss of the Yerkes National Primate Research Center in Atlanta complains that the bill defines “invasive” too broadly. It would prohibit his and other groups from sedating chimpanzees to perform brain scans or drawing blood for behavioral experiments and endocrinology studies. He calls these interventions “minimally invasive.”

Several scientific societies also oppose the ban. Alice Ra'anan, director of science policy at the American Physiological Society in Bethesda, Maryland, notes that existing government rules strictly regulate experiments on chimpanzees. “We can't afford to support an across-the-board ban,” says Ra'anan. “There are diseases that can only be studied in chimpanzees.”

Ajit Varki, a glycobiologist at the University of California, San Diego, who studies chimpanzees and disease but does not do invasive research himself, has long tried to find a middle ground between opponents and proponents of this controversial animal model. He says no research should be done on chimps that we would not do on humans. “On the other hand, I would no more think of banning all research on chimpanzees than of banning all research on humans,” says Varki. “That would be a bad idea for the future of either species.”

4. SOLAR PHYSICS

# Report Puts NASA's Solar Program Under a Cloud

1. Andrew Lawler

A panel of space scientists has given NASA low grades on an ambitious 10-year plan to study the sun and its impact on Earth. A new report* from the National Academies' National Research Council (NRC) says rising project costs and an inadequate budget pose “a serious impediment” to the field of heliophysics. NASA officials disagree with the academies' harsh assessment of the agency's progress on a 10-year research plan adopted 5 years ago, citing a pipeline filled with major missions and increased funding for studying the results.

The analysis, by a committee of the academies' Space Studies Board, is a midterm report card on the 2003 decadal plan that was requested by Congress. Although NASA receives average to good marks for its progress on many parts of the plan, it earns a D for making little progress on the Geospace Network, a program that would study the impact of solar variability on sensitive electronics used in satellites and ground-based power grids, and an F for failing to integrate its efforts with those of other disciplines and agencies, notably the Department of Energy.

Richard Fisher, who directs the heliophysics program at agency headquarters, acknowledges that the report may be “useful” but says he's disappointed that it included neither a clear scientific assessment of the current situation nor recommendations on what NASA might do better. “We would have welcomed such an assessment so as to better address … the allocation of scarce resources and flight-project decisions,” he says.

The saga of two major projects featured in the 2003 decadal study—the Solar Dynamic Observatory (SDO) and the Magnetospheric Multiscale (MMS) mission—illustrates the problems facing NASA and the field. Both launches have been delayed by some 4 years, and the cost of each has more than doubled. SDO, which will study the effect of the solar atmosphere on near-Earth space, is now set to be launched later this year at a cost of nearly $900 million—far more than the original$400 million. The cost of MMS, which will use four separate spacecraft to study the structure of Earth's magnetosphere, has grown from $350 million to$1 billion with a scheduled launch in 2014. “The resources … have not been used effectively,” says Daniel Baker, a space physicist at the University of Colorado, Boulder, who was on the original 2003 panel. “The result is disastrous.”

The cost increases have deferred deployment of the Geospace Network until later in the next decade. And NASA's decision in 2004 and 2005 to trim smaller programs such as Explorer because of shrinking budgets has deprived solar scientists of expected opportunities to put their instruments into orbit. “There's just not enough money,” says Roderick Heelis, a University of Texas, Dallas, physicist who co-chaired the 11-member NRC panel with Stephen Fuselier of Lockheed Martin's Advanced Technology Center in Palo Alto, California.

Fisher says the heliophysics program is in better shape than the academies' report suggests. SDO will be followed in 2012 by a series of spacecraft called the Radiation Belt Storm Probes, he notes, and NASA plans to launch the first satellite to orbit near the sun a year or so after MMS goes up. NASA's balloon and small-rocket programs are growing, he adds.

Heelis says the panel wants future missions designed to make the best use of the money that's available. But the forecast for funding solar exploration is cloudy at best. Under a long-term projection from the Bush Administration, the budget for heliophysics would drop from $831 million in 2007 to$598 million in 2010, before climbing to $747 million in 2013. The Obama Administration has not signaled what it plans to do. Colorado's Baker is encouraged by the strong interest in climate change research shown by White House officials and their awareness of the importance of space weather, two areas that could bolster NASA's program. But solar scientists worry that their field may be eclipsed by overruns in the Mars Science Laboratory, the push to build a massive new spacecraft to orbit Jupiter, and the need to restart the flagging Earth science program. “There's a zero-sum game mentality, which makes it hard for our aspirations to be met,” says Baker. 5. BIOSECURITY # Paul Keim on His Life With the FBI During the Anthrax Investigation 1. Yudhijit Bhattacharjee Hours after the first wave of the 2001 anthrax letters sickened a man in Florida—the first of five people to die in the attacks—geneticist Paul Keim got a phone call from the Federal Bureau of Investigation (FBI). Keim, of Northern Arizona University in Flagstaff, had 3 years earlier developed a genetic fingerprinting technique to distinguish between different types of Bacillus anthracis. The FBI wanted him to identify the anthrax strain the attacker had used. Keim and his lab continued to play a role in the investigation until last summer, when the FBI implicated U.S. Army researcher Bruce Ivins as the perpetrator of the attacks. In a recent interview with Science, Keim recounted some of the key moments from his involvement in the 7-year-long investigation. Some of his responses were edited for clarity. Q: When were you consulted about the case? P.K.: Shortly after Florida's Robert Stevens [the first victim] became ill, officials contacted me to find out whether he could have contracted anthrax from drinking water out of a stream in North Carolina, where he had been traveling the week before, or from exotic Oriental food stores. But in the wake of September 11, we were all suspicious that it was a follow-on terrorist attack. Q: How did your lab get involved? P.K.: The FBI wanted us to analyze the anthrax in Stevens's cerebrospinal fluid. An FBI scientist, Doug Beecher, called me on the afternoon of October 4 to let me know that the culture was already in the air: It was arriving in a business jet from Atlanta, where an identical sample was being analyzed at the Centers for Disease Control. My body went cold because I realized we only had a few hours to prepare for it. It was sundown when I drove to the commercial airport at Flagstaff. The airport officials let me drive out on the tarmac. I watched the jet land; an attractive blonde woman got off with a box containing the culture. It was a surreal experience. I felt like Humphrey Bogart in a scene from Casablanca. I put the box in my car and drove right back to the lab. The next morning, we called Atlanta to say that we'd determined the sample to be the Ames strain. Q: What came next? P.K.: Over the next few months, we analyzed anthrax from all the letters. After the FBI decided to pursue full genome sequencing of anthrax samples from labs all around the country and overseas to trace the source of the spores used in the attacks, we were contracted to prepare DNA from the samples. The DNA was shipped to The Institute for Genomic Research in Rockville, Maryland, for sequencing. Our lab also served as the repository for all of the samples. Q: What was it like to be collaborating with an investigation? P.K.: The conversion of an academic lab to a forensic lab was painful: We had to follow strict rules concerning the handling of evidence. Every little step in the process needed to have witnesses. But we took it very seriously; we were motivated by the fear of having a Johnnie Cochran cross-examining us in court. We were sent some 1500 samples. … The work pressure was very high. … At one point, people in the lab were starting to revolt. After we developed some real-time PCR assays to identify the samples, we were able to cruise through. Q: When did you learn that investigators were focusing on Bruce Ivins? P.K.: On 14 May 2008, when FBI agents and Justice Department officials revealed his name in the course of questioning me about the timeline for how the technology for fingerprinting anthrax had improved since the mid-'90s. Q: How did the interview unfold? P.K.: It was in a room at the Courtyard Marriott near the Washington Dulles airport, where I was attending a meeting of the FBI's Scientific Working Group on Microbial [Genetics and] Forensics. There were five FBI agents and officials from the U.S. Attorney's office. … I remember making a nervous joke. I said I've greased up my wrists just so I can slip out of my handcuffs when you throw me in the back of the van. … What they were trying to establish was how much Ivins would have known about the developments in fingerprinting [to distinguish between different strains]. They pulled out e-mails that Ivins and I had exchanged in 2001–2002 as part of ongoing discussions amongst anthrax researchers about the attacks. They wanted to know if I could tell, from those e-mails, if Ivins might have been attempting to cover his tracks. Q: What did you conclude? P.K.: I didn't see any smoking gun. I went back and looked at some other e-mails from him, and in one that he sent on 7 February 2002 to the group, he said, “The only place I know of that makes anthrax powder is the Dugway Proving Ground.” Q: Do you think Ivins was guilty? P.K.: I don't know. Q: Are all the samples still at your lab? P.K.: No, the FBI took them in June 2008. The agency flew a propeller plane from the East Coast to Flagstaff to transport them to another destination. Q: How can researchers learn more about the scientific work done on the case? P.K.: Scientists are committed to publishing all of the research. The goal is to package all of the papers into one journal so that the community can evaluate the quality of the science all in one place. 6. CHINA # Biologists Muscle Up With Major New Protein Facilities 1. Richard Stone* 1. With reporting by Hao Xin in Shanghai BEIJING—When molecular biologist Xu Rui-Ming gave up a plum professorship at New York University to return to China last autumn, he knew the move would entail sacrifices: a pay cut, for starters, and the need to acclimate to Beijing, one of the fastest growing cities in the world. But the opportunity to help build a research empire was impossible to resist. This month, Xu and colleagues here at the Institute of Biophysics (IBP) of the Chinese Academy of Sciences (CAS) will begin recruiting researchers for a National Laboratory of Protein Science (NLPS). In the spirit of Janelia Farm, the biomedical research haven in Virginia run by the Howard Hughes Medical Institute, the national lab will give a few dozen top-notch biologists generous contracts, access to top equipment, and protection from the vitality-sapping chase for research funding. Last year, Premier Wen Jiabao called for the creation of several dozen national labs; NLPS is among the first in the biological sciences. “We are the guinea pigs,” says Xu. They will get a leg up from an allied effort to lift biology boats countrywide. Science managers here and in Shanghai are divvying up$160 million for a National Core Facility for Protein Sciences that will be open to all Chinese researchers, including those at NLPS, and eventually to foreigners as well. “It's the first time in history that the government has funded a national facility in life sciences,” says cell biologist He Fuchu, director of the Beijing Proteome Research Center.

Quickest off the blocks should be NLPS. It's the brainchild of former IBP Director Rao Zhihe, now rector of Nankai University in Tianjin, who floated the concept in 2003. CAS has spent $45 million over 5 years instrumenting IBP. Next, “we need high-caliber researchers,” says Xu, a specialist on epigenetics who intends to recruit a significant number of the lab's initial 60 principal investigators from overseas. To sweeten the appeal, the national lab will give researchers a salary and 5-year grants and let them loose in a setting akin to Cold Spring Harbor Laboratory, where Xu worked for 13 years. “This is an absolutely new concept in China,” he says. Two-thirds of the initial recruits will be stationed at IBP and the rest spread around the country, like Howard Hughes investigators at their home institutions; the plan is to ramp up to 100 principal investigators, with a rising percentage located outside IBP. NLPS's budget is roughly$60 million a year.

## Personal black boxes

SenseCam grew out of a Microsoft Research project that aimed to create a “black box for the human body” which would record data that doctors might find useful if a person were in an accident, says Ken Wood of Microsoft Research Cambridge. In 1999, computer scientist Lyndsay Williams, then also at the same lab, suggested adding a camera to the device so it could double as a memory aid for mundane tasks such as finding lost keys.

In 2002, Kapur heard then-Microsoft CEO Bill Gates mention the project in a talk. Because his hospital is just a few miles from Microsoft Research Cambridge, it was easy enough for him and Berry to suggest using SenseCam prototypes for patients with memory problems due to Alzheimer's or brain injuries.

Clinicians who work with such people have typically focused on helping them with their prospective memory, i.e., remembering tasks to be completed in the future, such as keeping appointments. For this, the best aids are still simple tools such as checklists and alarm clocks. But for patients with difficulty recalling past events, clinicians have had little to offer beyond diary-keeping, a task many people, such as Mrs. B and her husband, complain is onerous.

In contrast, SenseCam records images passively, permitting a person to go about their day without interruption. The latest version is about the size and weight of a clunky mobile phone and appears to observe the world through two unmatched eyeballs. One is a passive infrared sensor, tuned to trigger the camera whenever another person passes by. The other is a wide-angle camera lens, set to capture most of the user's field of view. The device is also equipped with an ambient light sensor that triggers the camera when its user moves from one room to another, or goes in or out of doors. The camera can also be set to snap an image if the sensors haven't triggered a photo after an arbitrary number of seconds. A typical wearer might come home with 2000 to 3000 fragmentary, artless images at the end of a day.

It may be just those characteristics of the SenseCam images that make them so useful for memory rehabilitation and research, Kapur says. Like Conway, he suspects that the reason the images stimulate memory retrieval and possibly consolidation is because they mimic “some of the representations that we have” of past events in our brains.

To move beyond the initial case study of Mrs. B, the Addenbrooke's team, under the direction of neuropsychologist Georgina Brown, has followed five additional people with memory problems over a nearly 3-year period, exploring the difference between the memory boost provided by visual and written diary-keeping. Establishing a baseline of how fast these people lose their memories, the team asked each about an event every other day for 2 weeks after the event, and then again after 1 month and after 3 months. Then they asked the patients to keep a diary of a separate event and review it every other day during an initial 2-week assessment, but not during subsequent months. Finally, patients reviewed their SenseCam's images for 2 weeks following a third event.

The preliminary results suggest that SenseCam use strengthened these patients' memories more than diary-keeping did. A full analysis of the data is in preparation, says Brown, whose team plans to submit it to the journal Memory for a special issue devoted to SenseCam research.

In a recent, separate study, Mrs. B has repeated a version of her trial, this time incorporating a brain scanner. Researchers compared the activity in her brain as she tried to remember events she had either reviewed in her written diary or with personal images from her SenseCam. Mrs. B recognized about 50% of images taken at an event she had studied using a diary, but 90% if she had studied images instead. And brain regions associated with autobiographical memory were more active when she recalled events she had studied using SenseCam images than when she recalled the diary-studied event, Berry and colleagues report online on 13 March in the Journal of Neurology, Neurosurgery and Psychiatry.

The Addenbrooke's work represents just a few patients with varying causes of memory loss, but Berry notes that worldwide there are about 30 ongoing SenseCam studies of memory patients. Adam Zeman of the University of Exeter in the United Kingdom leads one. “I think the main interest [in SenseCam] is that it gives you an opportunity to look at memory in what you might call a more ecological fashion than laboratory stimuli generally do,” he says, and “it gives an opportunity to support and rehabilitate memory.”

## Memory walks

Normally, basic research precedes clinical studies, but the history of SenseCam has been the reverse. “The initial studies had a strong pragmatic aim,” says Kapur, “but certainly once we started to collect data, [psychologists] began to look at these things from a theoretical slant.” The question for cognitive scientists is whether SenseCam, or any similar wearable, point-of-view photographic device, can illuminate how healthy autobiographical memory works. Moulin, for example, has engaged volunteers to undertake memory walks in which they read a list of words while wearing the SenseCam. His student Katalin Pauly-Takacs has tested the participants' recall of the words on the day of their walks and then again 3 months later, with and without the help of SenseCam images. Their preliminary results suggest that volunteers remember more of the words from walks that they reviewed using SenseCam images.

Moulin's experiment is a nod to decades of autobiographical memory research, in which volunteers were tested on their ability to recall standard images or word lists they had previously seen. Some researchers suggest that the more personal nature of SenseCam images will be key to better studying autobiographical memory storage and retrieval. “Using SenseCam we can first, have more interesting stimuli and second, test [memory] processes that can generalize more easily to real life,” explains Roberto Cabeza, a neuroscientist at Duke University in Durham, North Carolina, who is also working with the device.

Despite SenseCam's more personal touch, there are no guarantees it will break new ground in memory research. “Whether or not it will tell us different principles or something novel is unclear,” says Larry Squire, a psychologist at the University of California, San Diego, who hasn't yet worked with the device.

William Brewer of the University of Illinois, Urbana-Champaign, notes that nobody really knows how best to evaluate SenseCam as a memory-consolidation aid or a retrieval cue. He and his graduate student Jason Finley have tested different aspects of memory using SenseCam images as cues, asking individuals how certain they are that they've seen an image before, or inquiring what they did after a certain image was taken. Such baseline studies, says Brewer, should help identify the most appropriate memory tests.

In addition to the seven Microsoft Research grants handed out in 2007, dozens of groups in cognitive psychology, clinical neuropsychology, education, and computer science are conducting research with borrowed SenseCams and independent funding. But there are no current plans to commercialize the hardware or the software from the SenseCam project—a fact that puzzles some fans of the device. In fact, to keep up with the growing demand for the devices, Microsoft would like to find another manufacturer willing to mass-produce the cameras, says Wood. Microsoft currently provides the cameras to only a limited number of patients under clinical supervision.

Even though he lobbies colleagues such as Moulin to try the device, Conway remains cautious about overselling SenseCam. There is still at least a decade's work ahead before “we can maximize its use for research and its use as an intervention scheme in helping failing memories,” says the 56-year-old investigator. “By that time, I'll need to wear one permanently, myself.”

12. NUCLEAR PHYSICS

# Fathoming Matter's Heart Unbound

Going to extremes, physicists hunt for "unbound" nuclei that don't stick together at all.

Going to extremes, physicists hunt for “unbound” nuclei that don't stick together at all

Ordinarily, the protons and neutrons in an atomic nucleus bind to one another with ferocious strength. The might of that binding explains why alchemists never found a way to change lead into gold: That would require prying apart the nucleus of one element to change it into another. Now, however, some physicists are eagerly creating odd nuclei that are so loosely built they are hardly nuclei at all. These rare beasts may provide a better understanding of the heart of matter.

In recent decades, experimenters have used particle accelerators to produce ever-more-unstable and fleeting radioactive nuclei. The new work pushes this exploration to its logical extreme with the creation of “unbound nuclei”—puffs of protons and neutrons so loosely jumbled together that there is literally nothing to keep them intact, not even momentarily. Some unbound nuclei could yield insights into stellar explosions that forge many of the heavy elements we see on Earth today. Others may stretch current theories of nuclear structure until they snap and thus yield new insights.

“In some sense, it's the most extreme test of our theories of nuclear structure,” says Nigel Orr of the Laboratory for Corpuscular Physics (LPC) in Caen, France, one of three dozen physicists who gathered recently for a workshop on the subject.* Sydney Gales, director of the National Heavy Ion Accelerator (GANIL) in Caen, says: “We are discovering that there is a whole new kind of loosely formed matter. The physics is completely new.”

So far, experimenters have snared a handful of the oddities. But interest in them is growing, as new accelerators now powering up or in planning should cough out many more.

## Crossing the line

The study of unbound nuclei crosses a conceptual frontier. Researchers map nuclei on a chart resembling a crossword puzzle, with the number of protons increasing from bottom to top and the number of neutrons increasing from left to right (see diagram). The 255 stable nuclei form a diagonal “valley of stability,” with their unstable radioactive brethren, less and more neutron-rich, to the left and right. In pursuing unbound nuclei, physicists strive to make nuclei ever richer in neutrons and, ultimately, to push across the “neutron drip line,” beyond which binding is impossible. On the near side of this line, each nucleus can minimize its energy, at least temporarily, by forming a tight clump. On the far side, a nucleus can always reduce its energy by falling apart, so there is no energy barrier to hold the thing together.

Interest in unbound nuclei builds on the study of other strange-but-bound nuclei, says Angela Bonaccorso, a theorist with the Italian National Institute of Nuclear Physics in Pisa. In the 1980s, scientists discovered that the bound nucleus lithium-11, which has three protons and eight neutrons, possesses an unusual structure in which two of its neutrons form a diffuse “halo” roughly 10 times the radius of the nucleus's core. Oddly, one halo neutron can't stick without the other: Remove one to form lithium-10 (three protons and seven neutrons) and the other flies out, too. Lithium-10 is unbound.

This means that the drip line zigzags as unbound lithium-10 lies between bound lithium-9 and lithium-11. Similarly, unbound beryllium-13 lies between bound beryllium-12 and beryllium-14, and unbound helium-7 and helium-9 interleave with bound helium-6 and helium-8. These interlopers are barely unbound; if their lowest energy state were just slightly lower, they'd stick together.

Such unbound nuclei challenge established theories of nuclear structure. Protons and neutrons cling to one another through the strong force, and most theories assume that each particle whizzes about in a static force field determined by the average distribution of all the others. Such “mean field” models predict the existence of energy “shells”—like those for the electrons in an atom—into which the protons and neutrons stack.

In these barely unbound nuclei, the mean-field approach comes up short. That's because the precise energy of the entire system depends on the details of the continual jumbling of the protons and neutrons. In that case, the notion of a shell—which assumes that the energy can be calculated from an unchanging average distribution of the particles—is no longer strictly valid, says Horst Lenske, a theorist at the Justus Liebig University Giessen in Germany. In fact, Lenske says, whether a nucleus is bound may depend on the precise and exceedingly complicated dynamics of all the interacting protons and neutrons.

If theorists can account for these dynamics, then they might better understand all nuclei, Bonaccorso says. The basic shell model has been embellished in various ways to help account for dynamical effects and deal with specific nuclei. Insights from unbound nuclei might tie these ad hoc fixes together more coherently. “We are constructing theories that are far more general,” Bonaccorso says.

## Depends on how you look at it

Studying unbound nuclei is not easy, however. The experiments require intense beams of radioactive nuclei to make these rare beasts and sophisticated detection schemes to snare the fragments released as they fly apart in less than a trillionth of a nanosecond. An unbound nucleus also presents a challenge because its properties depend on how it is produced.

For example, physicists expect that lithium-10 consists of a lithium-9 core with a halo neutron whizzing around it, and they want to know the exact “state” of that far-flung neutron. To determine that, LPC's Orr and his team fired beryllium-11 nuclei (with four protons and seven neutrons) through a carbon target in experiments at GANIL. A few of the collisions plucked one proton out of the beryllium nucleus to make a lithium-10 nucleus. That would instantly break into a lithium-9 nucleus and a neutron, and the experimenters would look for those pieces.

By measuring the energy with which the neutron and lithium-9 sped apart, researchers could probe their interactions; any pushing or shoving between them should create a peak in the energy spectrum. That spectrum would thus reveal the original state of the lithium-10 nucleus. Looking at the energy spectrum, Orr and his team found a broad peak that suggested the ejected neutron began in a state in which it had no angular momentum—a so-called s-state.

However, Haik Simon of the Helmholtz Center for Heavy Ion Research (GSI) in Darmstadt, Germany, and colleagues took a different approach to make lithium-10. They fired rare lithium-11 nuclei at a carbon target to try to knock one neutron out of the lithium nucleus. They then examined the resulting lithium-10 much as Orr did and observed an energy spectrum comprising three overlapping peaks. That suggests that the lithium-10 sometimes emerged in an s-state, sometimes in a p-state with one unit of angular momentum, and sometimes in a d-state with two units.

In spite of the incongruous results, there is an underlying consensus, Simon says. Both experiments show that, in spite of its infinitesimally brief existence, lithium-10 has a structure with well-defined energy states. They both also show that the lowest energy ground state is the s-state, as theory predicted. “Here we're getting quite clear,” Simon says. “It has now been resolved.”

But not all unbound nuclei are so straightforward. Takashi Nakamura of the Tokyo Institute of Technology and colleagues see signs of a more complicated situation in unbound beryllium- 13 (four protons and nine neutrons). In experiments at the Institute of Physical and Chemical Research's (RIKEN's) Nishina Center for Accelerator-Based Science in Wako, Japan, Nakamura and colleagues produced beryllium-13 by shooting beryllium-14 nuclei through a liquid hydrogen target to chip one neutron out of the incoming nucleus.

When the beryllium-13 fell apart, the researchers measured the energy spectrum of the rebounding pieces and observed a peak. But that peak seems to have the wrong energy and shape to be the expected s-state and may be a p-state, Nakamura says. That suggests that in beryllium-13, the quantum state of the beryllium-12 core is somehow altered, or “collapsed,” by the mere presence of the extra neutron, he says. Deciphering how the core is deformed is the sort of challenge theorists hope will lead to new insights.

## Stellar explosions run backward

A nucleus can also become unbound if it absorbs too much energy, and such overamped nuclei may play starring roles in stellar explosions. In a blast called a nova or in a more-powerful one called an x-ray burst, heavier nuclei form when lighter ones rapidly absorb protons, in the so-called “rp-process.” For example, a magnesium-22 nucleus can absorb an energetic proton to make an aluminum- 23 nucleus, which quickly spits out a photon to shed its excess energy.

Reproducing that interaction is difficult. However, RIKEN's Tohru Motobayashi and colleagues have found an easier way to run it backward. They fire aluminum-23 nuclei through a lead target. As an aluminum nucleus passes through a lead nucleus's electric field, it absorbs a “virtual” photon from the field. That unbinds the aluminum-23 and it splits into magnesium-22 and a proton.

The researchers measured the energy with which the magnesium-22 and proton flew away from each other. They found three overlapping peaks in the energy spectrum, the lowest at about 500 kiloelectron volts. Such details suggest that the forward process requires relatively high temperatures and densities and may play a bigger part in more-energetic explosions. “Our result implies that this process does not contribute so much to the nova but that it is important for the x-ray burst,” Motobayashi says.

The study of unbound nuclei is likely to grow, given the new facilities coming online or in planning, researchers say. Two years ago, the Nishina Center revved up the massive superconducting cyclotron that powers the lab's Radioactive Isotope Beam Factory (Science, 15 December 2006, p. 1678). When fully functional, it will provide beams more than 1000 times as intense as those at older facilities. GSI is building a synchrotron-based facility that will power up in the middle of the next decade (Science, 2 November 2007, p. 738), and in December 2008, the U.S. Department of Energy chose Michigan State University in East Lansing to host its proposed linear-accelerator-based facility (Science, 19 December 2008, p. 1777).

With much more intense beams, researchers should be able to climb drip lines to make unbound elements up to aluminum or silicon, says Tokyo Tech's Nakamura. Motobayashi says it should also be possible to study overenergized nuclei involved in an astrophysical progression called the r-process, in which lighter nuclei gobble up neutrons and which is thought to forge half the nuclei heavier than iron.

Exactly what unbound nuclei will reveal remains to be seen. Of course, the allure of the unknown is also leading nuclear physicists to test the bounds of their field.

• * Unbound Nuclei Workshop, University of Pisa, Italy, 3–5 November 2008.