News this Week

Science  16 Feb 2007:
Vol. 315, Issue 5814, pp. 920

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    MIT Hunger Strike: Sour Grapes, or the Bitter Taste of Racism?

    1. Yudhijit Bhattacharjee

    James Sherley, an African-American stem cell researcher at the Massachusetts Institute of Technology (MIT) in Cambridge, began a hunger strike last week to protest the school's denial of his bid for tenure. Claiming that racism played a part in his rejection, Sherley vows to maintain a daily presence outside the provost's office until MIT “admits” its bias and grants him tenure. His protest has divided the faculty and shined a spotlight on the dearth of tenured African-American scientists at the nation's elite research institutions.

    Public protest.

    James Sherley begins each morning outside the MIT provost's office before returning to his lab in the afternoons.


    Sherley, an associate professor, would have been the first tenured African American in the 41-person biological engineering department on a campus where 4% of the tenured faculty are under-represented ethnic minorities. Despite winning a $2.5 million Director's Pioneer Award from the National Institutes of Health for work on expanding lines of human adult stem cells, Sherley's request for tenure was denied in January 2005. Two internal reviews didn't change the decision. Sherley's list of complaints includes the allegation that he was given less laboratory space than other colleagues and that the department chair asked his wife—a departmental colleague who often clashed with Sherley—to weigh in on the tenure decision. He also believes that some of the hostility from his colleagues is fueled by his opposition to human embryonic stem cell research.

    “This is about ending the injustice that many African-American scientists before me have endured in silence,” says Sherley, who has vowed to drink only water and take vitamins and electrolyte supplements. “We're destroying careers, throwing talent away. It's not right, it's not smart, and I've decided to do something about it.” A day after Sherley began his strike, 11 professors including linguist Noam Chomsky circulated a letter demanding a review of the grievance process by a committee “composed of members from inside and outside MIT.”

    At the same time, some 20 department members have signed a statement contesting Sherley's allegations. “Was this absolutely the most perfect tenure review? I don't think there is such a thing,” says associate provost Claude Canizares, whose office asked a three-person committee to reexamine the tenure review. “But there was every attempt made to conduct the review with absolute fairness and integrity.”

    Sherley says he hopes his protest will hit the school “like a nuclear explosion” and force it to examine the question of institutional racism. Three days before he began his strike, MIT President Susan Hockfield announced “a comprehensive, rigorous, and systematic study of the impact of race on the hiring, advancement, and experience of minority faculty at the Institute.” Canizares says the study “take[s] advantage, in an ironic way, of the opportunity for discussion” created by Sherley's dramatic step. “It has energized people on campus to talk about the issue.”

    Sherley's hunger strike has also elicited support from two former MIT researchers, both African Americans, who say they encountered an adverse climate at the school. “Some of my experiences during that time undercut my status and represent the kind of racism that … Sherley is opposing,” wrote Sylvia Sanders, an assistant professor of biology between 1997 and 2001, in a 7 February letter circulating among MIT faculty. In one case, she says, a senior white professor told her that she had violated rules by bringing students into the faculty lunchroom. (There is no such rule.)

    Sanders's letter also cited the reaction of a white colleague after returning from a neuroscience meeting. “There were 10,000 neuroscientists there, and the only black people I saw were the waiters. Why is that?” he asked her during an elevator ride. When she responded by asking him, “Why are there so few African Americans at MIT?'” he replied: “Anyone can be a neuroscientist, but this is MIT!” Sanders now teaches third grade at a public school in Palo Alto, California.

    A second scientist, now a tenured professor of chemistry at the University of Illinois, Urbana-Champaign, believes that his failure to win tenure at MIT wasn't based entirely on an assessment of his contribution to science and the profession. “Judgments are constantly being made whether you are aware of them or not, and your idiosyncracies stand out much more if you are black than if you are white,” says Philip Phillips, an African American who spent 10 years at MIT's chemistry department. Phillips says he doesn't know “what happened behind closed doors” during his tenure review in 1991. “But I was told later that, for at least one faculty member involved in the decision, the fact that I wore baggy pants was an issue.”

    Sherley, whose appointment ends 30 June, hopes that his protest, begun 5 February, will force the university to confront such attitudes. Sherley says he's lost 14 pounds since beginning his regimen of spending every morning outside the provost's office before returning to his lab in the afternoon. He promises to continue the routine indefinitely. “Something has got to change at MIT,” he says.


    Bubble Fusion Researcher Cleared of Misconduct Charges, but Doubts Linger

    1. Robert F. Service

    Purdue University officials last week declared that an internal inquiry has cleared bubble-fusion researcher Rusi Taleyarkhan of allegations of research misconduct. The announcement appears to bring to an end a nearly yearlong row that has split the university. But with scientific claims and counterclaims still ricocheting around the community, the battle over tabletop bubble fusion shows no sign of dying down.

    “I feel vindicated and exonerated,” Taleyarkhan says. “It's been a pressure cooker for about a year.” Taleyarkhan is the chief proponent of sonofusion, the controversial idea that sound waves can collapse bubbles in a way that yields energy through nuclear fusion. If true, the research holds out the promise of a clean, limitless energy source. Taleyarkhan's purported evidence for sonofusion drew scientific skepticism from the start (Science, 8 March 2002, p. 1808), and early independent efforts failed to reproduce his results, including one in 2002 by his former colleagues at Oak Ridge National Laboratory in Tennessee.

    Last year, an article in Nature stoked the controversy when it reported that several of Taleyarkhan's colleagues at Purdue in West Lafayette, Indiana, where he moved full-time in 2004, had complained that he obstructed their work and tried to stop them from publishing results that contradicted his own. Other researchers continued to challenge Taleyarkhan on scientific grounds. Last year, one critic—sonochemist Kenneth Suslick of the University of Illinois, Urbana-Champaign—even raised the issue of possible scientific fraud in an e-mail to a Purdue research official.

    Purdue appointed a committee to review the matter, although just what allegations it investigated has never been made clear. In June, the university reported that it had completed an initial inquiry, and it launched a second one. Now, university officials say the inquiries have cleared Taleyarkhan of misconduct but that details of the findings, the charges, and even the makeup of the committees will be kept confidential, in keeping with the university's policies. “We're done with it,” says Purdue spokesperson Jeanne Norberg.


    Taleyarkhan has weathered the inquiries but now must convince his critics.


    Other experts both inside and outside the university say the process was shrouded in so much secrecy that it's impossible to know what the reviews entailed. “It's outrageous. I don't know what Purdue is doing,” says Lefteri Tsoukalas, a nuclear engineer at Purdue who initiated some of the allegations against Taleyarkhan. Tsoukalas said he spoke to the initial review committee last spring and was asked to resubmit written allegations in September, which he says he did. Yet, Tsoukalas says, neither he nor anyone else he knows was ever interviewed by the second panel. Suslick and Seth Putterman, a physicist at the University of California, Los Angeles, who headed a Defense Advanced Research Projects Agency-funded effort to replicate Taleyarkhan's work, say that they too were never contacted by the panel and are frustrated by its secrecy.

    Efforts to understand just what is going on inside Taleyarkhan's tabletop fusion devices remain equally controversial. Last spring, Taleyarkhan invited two separate teams to use his experimental setup at Purdue to see whether they could spot the telltale signs of fusion. The experiment is designed to use ultrasound to collapse bubbles in an organic solvent and force deuterium atoms in the bubbles to fuse, liberating either tritium and a proton or helium-3 and an extra neutron, plus lots of energy. In May, Ted Forringer, a physicist at LeTourneau University in Longview, Texas, ran the experiment with two undergraduate students using two different types of neutron detectors, both of which he says recorded significantly higher levels of neutrons than did controls. In June, William Bugg, a physicist emeritus at the University of Tennessee, Knoxville, also ran the experiment and says he too found evidence for excess neutrons.

    Neither of these experiments has been published in full, however. Stanley Milora, a physicist at Oak Ridge, says that in a write-up of the Forringer experiment that he's seen, electronic neutron counters called scintillation detectors only collected data for 60 seconds. In addition to longer data collection, Milora says he'd like to see evidence of where any proposed neutrons are coming from. If deuterium atoms are fusing in the collapsing bubbles, neutrons should hit the detectors just a few nanoseconds after the bubbles collapse and give off a burst of light. But Milora says there was no effort to track such correlations.

    Putterman, Suslick, and their colleagues did attempt to register such correlations, using Taleyarkhan's own engineering diagrams to construct their sonofusion apparatus. In a paper they published last week in Physical Review Letters, the researchers report that they detected no neutrons above background and saw no correlations between light flashes and neutrons.

    The bottom line, Milora says, is that most people won't believe bubble fusion is real until the work is verified outside Taleyarkhan's lab. “I think a fully independent reproduction of these results would turn a lot of people around,” he says. Until that happens, the chief form of energy produced by bubble fusion is likely to be heated arguments.


    New Swiss Influenza Database to Test Promises of Access

    1. Martin Enserink

    The world will soon know whether dozens of scientists and health experts meant business when they pledged to share crucial data on bird flu 6 months ago. Behind the scenes, a small group of experts has arranged for a brand-new influenza database, housed at the Swiss Institute of Bioinformatics (SIB) in Geneva, that plans to open the first week of March to turn their promise into reality.

    If all goes according to plan, researchers and H5N1-affected countries will use the database to reveal information about the virus to the world immediately, with the assurance that nobody can use their data to produce papers, drugs, or vaccines without their permission.

    About 15 flu labs currently share key genetic data about H5N1 in a password-protected compartment at the Influenza Sequence Database (ISD) at Los Alamos National Laboratory in New Mexico. That deal, under the auspices of the World Health Organization (WHO), came under fire last year from researchers, led by Italian veterinary virologist Ilaria Capua, who believes that everyone—not just a select group—should have access. Their criticism sparked the creation of the Global Initiative on Sharing Avian Influenza Data (GISAID), announced in a letter in Nature in August 2006 that was signed by more than 70 experts. The plan was spear-headed by media consultant Peter Bogner, until then unknown in the influenza world (Science, 25 August 2006, p. 1026).


    Peter Bogner has financed GISAID's efforts himself.


    A small group including Bogner, Capua, and Nancy Cox, head of the influenza division at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia, has now hammered out details of the plan. They reviewed final arrangements at a meeting in Munich last week. Anyone can get access to the new database, provided they register, log in, and accept an agreement limiting their use of the data, Bogner says. Those who provide data have 6 months to take care of patents and scientific publications; after that, the information will be entered into three large public databases.

    Bogner declined to provide details of the user agreement, which will be made public shortly. But these rules—and whether they're followed—will be crucial to GISAID's success, says Albert Osterhaus of Erasmus University Medical Center in Rotterdam, the Netherlands. As a signatory to the Nature letter, Osterhaus says he's “committed in principle” to depositing information in the database, “but I want to see the exact terms first.” WHO has not been involved in the plan but welcomes it, says David Heymann, head of the agency's flu efforts.

    SIB Director Amos Bairoch says that when GISAID's database kicks off, it will be filled with decades' worth of influenza data from humans, birds, and other species. Bairoch believes Switzerland's famed neutrality will help win over countries reluctant to contribute to a U.S.-sponsored database.

    ISD head Catherine Macken says researchers may prefer GISAID because it's free of charge—but she's okay with that. The bad press ISD has received because of the H5N1 compartment has been “a nightmare,” she says. “If someone else wants it, they're welcome.” “A sense of civic duty” led Bogner to bankroll the entire operation so far with his own money. But corporate backers, which he declined to name, are interested in helping out, he says.

    The issue of influenza sharing made fresh headlines last week when Indonesia announced it would no longer share viral samples of H5N1 with WHO without a so-called Material Transfer Agreement that limits commercial use of the virus. But even if Indonesia no longer shares viruses, Bogner says he has guarantees that it will keep sharing its H5N1 sequence data with GISAID.


    Amid Debate, Gene-Based Cancer Test Approved

    1. Jennifer Couzin

    In the chaotic and rapidly expanding field of “personalized medicine,” dozens of companies aim to create tests that read a disease's biochemical tea leaves and anticipate the course it will take. The predictions, which often rely on gene expression patterns, can have a momentous effect, for example, prompting doctors and patients to eschew chemotherapy when a test suggests that a breast cancer has a low risk of recurring.

    But as these largely unregulated tests move into clinical use, researchers are asking some fundamental questions: Are they based on sound science? And can physicians really interpret the results?

    Last week, the U.S. Food and Drug Administration (FDA) stepped full force into this debate, issuing its first-ever approval of a multigene prognostic test and 2 days later holding a contentious meeting to discuss more stringent oversight of this area. Called MammaPrint, the test approved by FDA was developed by Amsterdam-based Agendia and aims to predict a breast cancer's risk of recurrence. MammaPrint is currently available in Europe, South America, and elsewhere; Agendia says it has performed more than 5000 tests so far.

    In the United States and Europe, diagnostics such as MammaPrint and another breast cancer prognosticator called Oncotype DX are not generally approved the way drugs and devices are. Instead, in the U.S. they're considered laboratory tests and are allowed on the market with little scrutiny of their science when performed under the auspices of a single lab. Agendia sought FDA approval of MammaPrint in part on the agency's request, and in part to reassure physicians that the test is sound, says the company's co-founder and chief scientific officer, René Bernards. Based largely on results from 302 European breast cancer patients, FDA expressed confidence in MammaPrint's quality.

    But now FDA wants to extend its oversight to many more gene-based tests. In September, the agency released a draft document suggesting that many prognostic tests should be regulated as medical devices, which would vastly expand the agency's oversight of them. This policy would cover many candidate tests, including, possibly, a method for identifying the primary source of metastatic cancer and a blood test to determine whether a transplanted heart is being rejected. “We had concerns” about this class of products, said Steven Gutman, FDA's director of the Office of In Vitro Diagnostic Device Evaluation and Safety, at last week's meeting in Gaithersburg, Maryland. Accuracy is one concern, he says, as is a “lack of transparency” about how the tests are performed. FDA is accepting comments until 5 March.

    Next generation.

    Cancers have long been evaluated by direct observation (left column); a new test uses gene expression to judge the risk of recurrence (right column).


    At FDA's meeting, many companies and some patient advocacy groups argued against FDA's proposed policy. They suggested that requesting more extensive clinical trials would impose a financial burden that diagnostics outfits can't afford and possibly add a decade's delay. “We can't wait that long,” says Charles Perou, a geneticist at the University of North Carolina, Chapel Hill, who is trying to commercialize a breast cancer prognostic test but did not attend the meeting.

    Two of the breast cancer tests that are farthest along, MammaPrint and Oncotype DX, have settled on a middle ground: The companies are marketing their tests to doctors on the basis of retrospective studies of stored tissue while long-term clinical trials of breast cancer patients run simultaneously. MammaPrint uses a 70-gene signature to stratify women with breast cancer that hasn't spread (typically one of the groups that may avoid chemotherapy) into “low-risk” or “high-risk” categories. Oncotype DX relies on a 21-gene analysis to help inform clinicians whether patients with localized, estrogen-receptor-positive cancer are at risk of relapse. And although CEO Randy Scott of Genomic Health, the Redwood City, California, company that makes Oncotype DX, believes that these tests should be developed as “you would develop a drug,” he does not think they should be regulated as such. “We're not injecting anything into the body,” he says.

    But some physicians see significant risks. “If I withhold lifesaving therapy from a patient because of a bad test, that's every bit as bad as if I gave her a bad drug,” says Daniel Hayes, a breast cancer specialist at the University of Michigan, Ann Arbor, who helps run an Oncotype DX trial.

    Physicians such as Hayes, meanwhile, continue to puzzle over what some prognostic tests are really telling them. In cancer, “it may be that at 5 years, one group has a 20% relapse rate, the other has a 75% relapse rate, but what's going to happen at 10 years? Are we measuring the chance of metastases, or the rate?” asks Larry Norton, deputy physician-in-chief for breast cancer programs at Memorial Sloan-Kettering Cancer Center in New York City. He also notes that many of the genes used by these tests are linked to tumor growth, despite emerging data that other genes, such as those that affect inflammation, could also be critical.

    Another concern, says Hayes, is that because many studies were designed to answer a simple question—did the patient live or die?—some of the data could be misleading. A participant whose tumor responds unusually well to chemotherapy, for example, may be misclassified as one with a positive prognosis from the outset. In such a case, says Hayes, a test result could lead to “withholding the very agent that made their prognosis good.”


    In Europe's Mailbag: A Glossy Attack on Evolution

    1. Martin Enserink

    PARIS—It's the most gorgeous-looking attack on evolution seen in a long time: That's the consensus among European scientists who in recent weeks have received unsolicited free copies of the Atlas of Creation. The 768-page, lavishly produced tome was written by Harun Yahya, a Turkish author who denounces Darwinism as the source of many evils, including 9/11. Its publisher has sent hundreds if not thousands of copies of the book to researchers in at least four countries in Western Europe.

    A source of amusement to some, the book has troubled and outraged others—especially in France, where a French translation landed in the mailboxes of hundreds of high school directors and librarians. “This is a nasty attack on our education system,” says evolutionary biologist Armand de Ricqlès of the Collège de France, who worries that the book might touch off a battle over the teaching of evolution in Europe. French Education Minister Gilles de Robien swiftly warned schools to keep the book out of pupils' hands.

    Mass mailing.

    Schools in France have received a slick volume that purports to disprove evolution science.


    Harun Yahya is the pen name of Adnan Oktar, the head of the Foundation for Scientific Research (BAV) in Ankara, which has promoted Islamic creationism since 1997 (Science, 18 May 2001, p. 1286). Yahya is credited with hundreds of books; he is “more like a brand name” for a group of writers he leads, says Taner Edis, a Turkish-born physicist at Truman State University in Kirksville, Missouri, who has studied Islamic creationism.

    Yahya accepts that the world is billions of years old but rejects the concept of evolutionary change. More than 500 pages in the Atlas of Creation (the first in a series of seven volumes) are filled with pictures of fossils, accompanied by modern-day organisms that look strikingly similar—proof, Yahya says, that evolution theory is false. It's an “absurdly ridiculous” logic, says Gerdien de Jong, one of five biologists at Utrecht University in the Netherlands who received a copy.

    Within Turkey, BAV has been “quite successful” in promoting creationism, says biologist Aykut Kence of the Middle East Technical University in Ankara. One recent survey found that more than 50% of biology teachers in secondary education “are not sure about the validity of evolution,” says Kence. Yahya's books have also been translated into Arabic, Urdu, and other languages of the Islamic world.

    How BAV can afford mass distribution of books, as well as a plethora of DVDs and Web sites in several languages, is unclear. Rumors abound—for instance, about Saudi or U.S. backers—but Turkish law makes finding out the facts very difficult, Edis says. In an e-mailed response to questions, a spokesperson for Yahya declined to address finances. He added that France “can gather up and burn all the books, just like in the days of the Nazis, … yet the collapse of Darwinism cannot be prevented by prohibitions and bans.”

    French scientists say they need to operate carefully so as not to inflame tensions with France's sizable Muslim minority. But a response is needed, says de Ricqlès, if only to arm teachers with counterarguments. Kence says he and others have tried to promote evolution, but he says he never engages in direct debates with creationists, because that would enhance their credibility.

    Meanwhile, some readers were trying to find new uses for Yahya's book last week. Ecologist Michael Hassell of Imperial College London says he's using the 5-kilogram opus as a lamp stand. His colleague Peter Knight, another recipient, says he donated his copy to his ecology group—“I hope they found it was biodegradable and recyclable,” he says.


    Health and Safety Research Slated for Sizable Gains

    1. Robert F. Service

    Heeding calls for increased basic research on the health and environmental implications of nanotechnology, the Bush Administration has proposed a $3-million-a-year network of academic centers to pursue the topic and disseminate the findings. But that network, part of President George W. Bush's 2008 budget request sent last week to Congress, doesn't address what many consider a bigger problem for the field: the lack of research tied more tightly to the development of new U.S. regulations.

    In 2006, the federal government funded $38 million in research on nanotechnology environmental health and safety. That is likely to grow to $46 million this year (Congress was expected to take final action on the federal budget this week), and the president's budget would boost it to $59 million. At the cornerstone of this new push is a network of centers, funded by the National Science Foundation and modeled after existing NSF networks.

    Vicki Colvin, a chemist at Rice University in Houston, Texas, who directs Rice's Center for Biological and Environmental Nanotechnology, says that she believes spending more money on basic research and a network of centers is the right way to go. “It's great news,” Colvin says. She notes that nanotechnology remains in its early development despite some 380 products containing nanomaterials that are already on the market. At this stage, she says, it's important to learn more about how nanomaterials interact with biological systems.

    The NSF network proposes to do just that, she says, by investigating how the structure of a wide array of different nanomaterials affects their environmental behavior. “Forming a network that permits everyone to exchange supplies and methodology will really fast-forward this field by a couple of years,” she says.

    But not everyone agrees that basic research is the best investment the government could be making to understand the environmental health and safety aspects of nanoproducts. Nanotechnology “has stopped being a pure science project,” says David Rejeski, who directs the Project on Emerging Nanotechnologies at the Woodrow Wilson International Center for Scholars in Washington, D.C. “Nanotechnology is being commercialized at a very fast pace right now. You've got to position the science ahead of that.”

    Rejeski argues that U.S. regulatory agencies, such as the Environmental Protection Agency (EPA) and the National Institute for Occupational Safety and Health, are struggling to keep up with the questions being raised about how best to regulate nanotech products entering the market. And although EPA would receive $9.6 million in 2008, up from $3.7 million in 2006, Rejeski argues that considerably more is needed.

    Last September, both Republican and Democratic leaders of the House Science Committee called for expanding the research needed for regulatory agencies to ensure the safety of nanomaterials in the environment. And supporters have reason to believe legislators will heed that plea: In every year since the U.S. National Nanotechnology Initiative began in 2001, Congress has topped the president's request.


    Radcliffe Historian Named Harvard President

    1. Andrew Lawler

    Harvard University's search for a new president to succeed the controversial Lawrence Summers ended this week with the appointment of a Radcliffe dean and civil war historian. Drew Faust, 59, will become the first woman to lead the oldest and wealthiest university in the United States. She emerged as the top candidate in the yearlong search after Thomas Cech, biochemist and president of Howard Hughes Medical Institute, withdrew his name from consideration earlier this month.

    She's the one.

    Drew Faust is Harvard's new president.


    After her selection was announced on 11 February, Faust spoke out strongly in favor of a new initiative to increase interdisciplinary work in Harvard's extensive science program (Science, 26 January, p. 449) and added that she wants to break down the barriers between the sciences and the humanities. She takes over 1 July from interim president Derek Bok.

    Some search committee members wanted a physical or biological scientist for the post, but friends and colleagues of Faust insist she has a good track record in supporting research in her current job as dean of the Radcliffe Institute for Advanced Study, a school within Harvard. “She is not a scientist, but I am certain she has the ability to ably lead the university's expansion of its science efforts,” says Barbara Grosz, a computer scientist and Radcliffe science dean who has worked closely with Faust.

    “Right from the start, I had many people say to me, ‘You should give up on having science at Radcliffe,’” Faust says in an article appearing in the most recent issue of the Radcliffe Quarterly. “It was clear to me from the outset that science needed to be an important commitment for the new institute.” It also runs in the family: Her husband, Charles Rosenberg, is a historian of medicine and science at Harvard.

    Female faculty members at Harvard said they were delighted with the appointment of Faust to succeed Summers, whose controversial comments about women's ability to succeed in the sciences contributed to his resignation last February. “This is an inspired choice,” says Evelyn Hammond, senior vice provost for faculty development and diversity and a historian of science, who has known Faust for years. “She has extraordinary leadership qualities and enormous integrity.”

    In a press conference after she was named, Faust praised Summers, an economist and former treasury secretary in the Clinton Administration, for his analytical skills. But then she added, “I think women have the aptitude to do anything, and that includes being president of Harvard.”


    Science Adviser Says That Pruning Is the Key to a Healthy Budget

    1. Jeffrey Mervis
    Balancing act.

    John Marburger says some research areas were left behind during a “ramp-up of expensive programs” at NIH.


    The U.S. science community needs to figure out how to live within its means, says John Marburger, science adviser to President George W. Bush. In particular, he believes biomedical scientists need to curb their appetite for federal funding and space scientists must learn to turn off a mission before building and launching a new one.

    Speaking last week to Science about the president's 2008 budget request to Congress, Marburger defended the Administration's plans to give a sizable boost to a few agencies while starving most of the rest of the science establishment (Science, 9 February, p. 750). He says that “no president has been a stronger supporter of science and technology as a way to benefit society,” and he rejects complaints from science lobbyists that the budget request threatens the health of the U.S. scientific enterprise.

    “I think the overall federal scientific enterprise is well-funded,” Marburger says. “But there's been a ramp-up of expensive programs in some areas, while important programs in other areas are underfunded.” He notes that the American Competitiveness Initiative, first proposed last year, attempts to correct that imbalance in the physical sciences by boosting the budgets of the National Science Foundation (NSF), the Department of Energy's (DOE's) Office of Science, and the core labs at the National Institute of Standards and Technology. And he says that other agencies can thrive with their current budgets by setting priorities and sticking to them.

    Marburger was scheduled to testify this week before the House Committee on Science and Technology, kicking off the yearlong budget cycle. And although the Democratic Congress will surely revise the president's request for science and every other sector of federal spending, Marburger's comments, edited for space, shed light on the nature of the government's $55 billion commitment to basic and applied research.

    On the National Institutes of Health (NIH) budget

    “I think they have a structural problem, and I don't have a quick answer. … There is no way the federal government can ever satisfy the demands created by the doubling of the NIH budget [between 1998 and 2003]. It's led to what I call an unregulated research market, with booms and busts that are beyond the ability of the government to control.

    [At the same time,] NIH funding got way out of step with funding for the physical sciences. Biomedical research is funded much closer to the level of its needs than are the physical sciences. And there are imbalances within the biomedical research enterprise in which it's not clear that the pattern of expenditures matches the importance of the research. A lot of its $28 billion budget is aimed at treatments and therapies for specific diseases rather than basic cell biology and molecular biology, which raises the question of whether we're spending enough on basic research. The leadership understands these issues, and the director's Roadmap addresses these challenges.

    On NASA's budget crunch

    “Large space science programs face two fundamental problems. The first is the inability to make accurate cost estimates early in the life of the program. Once the price starts to go up, the agency has to either cancel the program or come up with more money. And the money is very hard to find; most of the time, you can't do it without digging into other programs.

    Second, the programs are sustained for longer than expected. So if you meet your goal of a certain number of launches per year, and those missions are sustained for a longer period of time, eventually something has to give. Do you know how many space science platforms are active right now? You might guess one or two dozen. The actual number is 55, which is a lot. We are spending a lot of money on space science—far ahead of everybody else in the world. But there needs to be a better appreciation of the need for strategic management of those assets.

    On better project management

    “We need new financial models for addressing the transition from construction to operation of a major scientific facility and for deliberately phasing out programs that are expensive once they have accomplished their mission. We can't expect them to last forever, because we can't afford them. We need to continually renew our infrastructure to keep up with what's happening in the rest of the world.

    Industry faces a similar challenge. It's a hard decision to shut down an operation that is profitable and productive and invest in new facilities that will be more productive. But it has to be done. … Look at the Hubble [Space Telescope]. We probably made the wrong decision, decades ago, to have it maintained by the space shuttle, because it turned out to be much more expensive than anybody realized. We could have launched many other science platforms for the price of maintaining one Hubble.

    And the problems associated with lifecycle planning estimates are not unique to NASA. NSF has experience with this, too, but as its projects become larger and more complicated, the management problems become harder. DOE may do the best job. It has phased out aging facilities before it builds new ones.

    We are America. We should be able to manage these projects.


    Cases of Mistaken Identity

    1. Rhitu Chatterjee*
    1. Rhitu Chatterjee is a science writer in Washington, D.C.

    For decades, biologists working with contaminated or misidentified cell lines have wasted time and money and produced spurious results; journals and funding agencies say it's not their job to solve this problem


    In the 1980s, when he was a postdoctoral fellow at the Scripps Research Institute in San Diego, California, Reinhard Kofler received what was supposed to be a human cancer cell line from a collaborator. “We cultured it, we cloned genes into it,” he recalls, then “[we] genotyped it and realized it was 100% mouse.”

    After scores of similar experiences with misidentified cells, Kofler and his colleagues at the Tyrolean Cancer Research Institute in Innsbruck, Austria, now authenticate every line as soon as it arrives at the institute. And periodically afterward, they use a simple, cheap, quick, and reliable DNA fingerprinting technique to verify that each cell line continues to be what it should be. “It's an absolute must now,” says Kofler. His lab “repeatedly” encounters problems with cell line contamination, and without this constant vigilance, Kofler says, “I wouldn't be confident about our work.”

    Not every biologist is so wary. A 2004 survey of nearly 500 biologists by Gertrude Buehring of the University of California, Berkeley, and her colleagues, showed that less than 50% of researchers regularly verify the identities of their cell lines using any of the standard techniques such as DNA fingerprinting. “Everybody is in denial” about the widespread problem of cell line cross contamination, says Charles Patrick Reynolds of the University of Southern California and the Children's Hospital Los Angeles' Institute for Pediatric Clinical Research, who establishes new pediatric cancer cell lines and tests potential cancer drugs on existing lines.

    Early warning.

    HeLa cells have contaminated scores of cell lines for more than 4 decades.


    Indeed, many studies have shown that a surprisingly large number of cell lines have become contaminated, often by older, more well-established cancerous cells. For example, according to a 1999 paper by Roderick MacLeod and his colleagues at the German Cell Bank (DSMZ) in Braunschweig, 18% of 252 lines donated to the bank were misidentified or contaminated. The extent of the problem “always seems to come as a surprise for people,” says John Masters of University College London, president of the European Tissue Culture Society.

    And even though biologists read and hear about cross contamination, “people just think that this is not a problem in my lab,” says Reynolds. If contaminated cell lines are used merely as “test tubes” to express proteins, a lab's work may not be affected. But, say Masters and others, research with contaminated lines continues to obscure potential drug leads and generate a large amount of artifacts in the scientific literature.

    Troubled by this ongoing problem, Roland Nardone, a cell biologist and professor emeritus at the Catholic University of America in Washington, D.C., has taken it upon himself to become the Paul Revere of cell contamination. In a recent white paper chastising the scientific community, Nardone calls for stricter policing of cell identities. He argues that journals and funding agencies such as the U.S. National Institutes of Health (NIH) should mandate authentication of cell lines.

    Several professional groups—including the Society for In Vitro Biology, the European Tissue Culture Society, and the American Society for Cell Biology—have endorsed the white paper, as have several cell repositories. But journals and NIH are wary of taking on the role of cell cop, and Reynolds is skeptical that Nardone will succeed where he and others have failed. “No amount of passioned discussion by myself or Dr. Nardone will fix what has been and continues to be a widespread problem,” he says. Merely suggesting what needs to be done, Reynolds adds, “is a long way from people actually doing it.” Kofler cites his own record as a cautionary tale: “We have started doing this [regularly fingerprinting lines] only 5, 6, or 7 years ago. Before that, even we were lazy.”

    Murphy's law

    How do cell lines assume secret identities, and why does it happen so often? “It's like Murphy's law,” says Kofler. “Everything that can go wrong will go wrong. It's just a matter of time.” Although most researchers are aware of the possibility of contamination and cautious when handling cells, accidents happen. Cell lines get mislabeled or contaminated with fast-growing cells that can in no time take over the original lines.

    The only way to prevent cross contamination is to spot it before it spreads. In 2001, Masters, who has been advocating for increased awareness of the problem for decades, published a description of a DNA fingerprinting technique that has become the standard tool for authenticating cell lines. When a line is established, it is crucial to record the donor's genetic profile and then do the same for the new line, says Masters. If this is done and the fingerprints made available publicly, it would provide other scientists with an authentic signature to verify the identity of the lines. Reynolds and his colleagues recently estimated the cost for a single DNA fingerprinting experiment to be $30. “It's so cheap, so obvious, so trivial, and yet it's not being done,” says Masters.

    Ignoring history

    The roots of the contamination problem go back to the beginning of studies with cell lines. Between the mid-1960s and the early 1980s, Walter Nelson-Rees of the Cell Culture Laboratory of the University of California, Berkeley, at Oakland found more than 40 different cell lines—both human and animal—cross-contaminated by the HeLa line, the first human cell line to be grown successfully in a laboratory. By the time he published his findings, there were already hundreds of papers describing research using the contaminated lines.

    Nelson-Rees made it his personal mission to warn others about the dangers of HeLa contamination. But the scientific community mostly reacted with hostility, and Nelson-Rees eventually gave up (see sidebar). No one was willing to withdraw their papers or lose their credibility—and most researchers continued using the contaminated lines. Nardone, Reynolds, Kofler, and other researchers are worried that history is being repeated, especially because the number of new cell lines has proliferated dramatically.

    In 2003, MacLeod and Hans Drexler of DSMZ and their colleague, Yoshinobu Matsuo, then at Fujisaki Cell Center in Okayama, Japan, checked the identity of 550 lymphoma-leukemia lines collected from researchers around the world and found 15% of them to be contaminated, mostly with faster-growing, well-established cell lines. In a letter in the 23 February 2006 issue of Nature, they estimated that 29% of all human-tumor cell line submissions to the DSMZ include cross contaminations. Because of the small sample sizes, these figures are, at best, “a significant underestimate,” says MacLeod.

    Estimating the real extent of the problem is difficult; there are far too many cell lines being established every year, and very few of them ever get their identities profiled. Repositories such as the German Cell Bank and the American Type Culture Collection (ATCC) profile every line in their labs. But most new lines are established in individual labs and from thereon are freely exchanged between labs, rarely having their identities checked. “These cell lines never pass through our doors, so they are never subject to accurate authentication,” says MacLeod. He and his colleagues have found that about 90% of scientists ignore or refuse a cell bank's request to send in new lines, and MacLeod argues that depositing lines should be required so that DNA fingerprints can be established and stored for future verification attempts.

    Researchers sometimes publish papers on individual mix-ups, hoping to warn the rest of the community about a particular cell line. But these warnings are typically restricted to specialized journals and fail to grab the attention of the larger scientific community. For example, Mordechai Liscovitch, a cancer researcher at the Weizmann Institute of Science in Rehovot, Israel, says he and his lab wasted 3 years because they hadn't noticed a publication revealing that the two breast cancer lines they were studying were not actually related—a fact the U.S. National Cancer Institute knew and attempted to publicize, although it continues to use and distribute the contaminated lines for drug testing (see sidebar, p. 929).

    A birthday resolution

    Nelson-Rees may have failed to stop the spread of HeLa cells, but Nardone is taking up his battle. The retired director of R/M Nardone Associates, a biotechnology training company, Nardone has for more than 2 decades educated graduate students and postdocs at NIH about cell culture techniques. “Each year, I give a lecture on cross contamination,” he says. “And each year, I get the same blank stares that tell me they aren't adopting the techniques.”

    In 2005, he happened to give this lecture on his 77th birthday. After the class, when his son asked him whether he had a birthday resolution, Nardone realized that he was “so damn mad” about the reluctance of scientists to acknowledge the seriousness of the problem that he decided to do more than give an annual talk to a few biologists.

    Several weeks later, Nardone put together a white paper titled Eradication of Cross-Contaminated Cell Lines: A Call for Action. “Clearly, the current situation is intolerable and requires a broad, coordinated effort involving those who do research, fund research, publish findings of research, and educate researchers,” he writes.

    Nardone's “call for action” seeks two broad changes: more regulations and increased education efforts. Nardone argues that journals and funding agencies should impose strict rules on researchers, forcing them to submit proof of cell line identity along with their manuscripts and grant proposals, respectively. This, he says, has to be supplemented by renewed education efforts to increase awareness of the cross-contamination problem, especially among younger researchers who are unfamiliar with its history.

    The journals and agencies targeted by Nardone seem to embrace his warnings but not his solutions. In an e-mail, Sally Rockey, deputy director of NIH's Office of Extramural Research, told Science that “NIH is aware that contamination of cell lines is a serious issue that can result in loss of biological products and render research worthless. … The career and reputation of scientists can be affected if research is conducted using contaminated cell lines.” Yet, Rockey argues: “It would be impractical to require authentication as a condition of award as cell lines are used routinely in thousands of basic science studies that NIH funds. … NIH believes that professional societies and scientists themselves should be driving the profession toward best practices in avoiding cell culture contamination instead of placing the responsibility on the funding agency.”

    Journals also hesitate to assert authority. “This is a requirement that would be imposed by the field, not by the journal,” says Science Deputy Editor for Biology Katrina Kelner. “We do not have an explicit policy but will certainly keep our eye on this if it is something that becomes a standard.” Nature did recently mandate DNA fingerprint data for papers reporting new human embryonic stem cell lines, but this policy doesn't extend to all cells. “I think we would agree with the sentiment” in the white paper, says Natalie DeWitt, a biology editor at Nature. But “you can't just suddenly say we need to verify cell lines; we don't have labs in our offices, and we can't check the lines ourselves and say it's from hamster and not from mouse.”

    Identity theft.

    DNA fingerprinting of these cancer cell lines shows that most, if not all, are identical to the chronic myelogenous leukemia line K-562. RS-1, for example, had been thought to be an acute myelogenous leukemia line.

    CREDIT: DREXLER ET AL., LEUKEMIA 17 417 (2003)

    Rebecca Chasan, executive editor of the Journal of the National Cancer Institute (JNCI), says reviewers sometimes raise questions about cell line identity, but after reviewing Nardone's white paper, JNCI may take a firmer line. The journal is planning to begin asking authors to confirm that they have authenticated their lines. Some issues need to be worked out, however. For example, should that request come before or after a paper undergoes review? “If a paper has gone through the peer-review process and the authors aren't able to confirm the identity of the cell line, it's not yet clear what we would do,” says Chasan. If the genetic signatures of all established cell lines were available in a public database, then it would be easier for journals to step in, notes DeWitt.

    As journals wrestle with the problems posed by cell line mix-ups—Reynolds goes so far as to estimate that journals would have to retract 35% to 40% of their previously published cell biology papers to weed out invalid data—some organizations are trying to help in different ways. The Society for In Vitro Biology will hold a symposium at its 2007 annual meeting in which Yvonne Reid of ATCC will talk about how contamination can be prevented. Nardone, Masters, and Joseph Perrone of ATCC are also organizing a conference to discuss standards and guidelines that could lead to profession-wide compliance for authentication. And ATCC, which has for decades sold lines overtaken by HeLa, recently decided to stop routinely distributing the lines, except for special requests from researchers. But these efforts will have limited effect, says Nardone, if journals and grant-awarding agencies won't mandate cell line authentication. What biologists need, he concludes, is a “stick saying that if you don't do this, there will be a consequence.”


    When 60 Lines Don't Add Up

    1. Rhitu Chatterjee*
    1. Rhitu Chatterjee is a science writer in Washington, D.C.

    Even the bedrock of present-day cancer research, the NCI-60 panel—a group of 60 cancer cell lines maintained by the U.S. National Cancer Institute (NCI) and used widely for both basic research and drug discovery—has not escaped the scourge of cross contamination. In the late 1990s, Mordechai Liscovitch of the Weizmann Institute of Science in Rehovot, Israel, had obtained from the institute the breast cancer line MCF-7 and its drug-resistant daughter line, once known as MCF-7/AdrR (for Adriamycin resistance)—both part of the NCI-60 panel. A few years ago, a comparison of the lines in his lab revealed certain biochemical differences that illustrated how cancer cells become resistant to drugs. Three years of work with these lines had unfolded “a nice story,” says Liscovitch.

    Early in 2001, he submitted a manuscript on the work to Oncogene and was awaiting its publication. Then, one of his students stumbled upon a 2000 letter in the Journal of the National Cancer Institute, saying that DNA fingerprinting had revealed that MCF-7 and MCF-7/AdrR were in fact unrelated; Liscovitch and his team immediately realized that their interpretations in the upcoming paper were no longer valid. Disappointed at the years of wasted time and effort, they withdrew the paper before it went to print. “It was a big blow for us,” Liscovitch says.

    Not only was MCF-7/AdrR unrelated to MCF-7, but it also turned out to be identical to an ovarian cancer cell line also in the NCI-60 panel. That's not the only case of mistaken identity within the NCI-60 panel. The SNB19 and U251 lines, once thought to be distinct central nervous system lines, are identical to each other and came from the same individual. And MDA-MB-435, a prevalent model for metastatic breast cancer, is identical to the panel's melanoma line, M14. NCI has tried to trace the history of MDA-MB-435, which was originally established in 1976 at M. D. Anderson Cancer Center in Houston, Texas. NCI found that the NCI-60 panel's version is the same as a sample of the line originally deposited at a cell bank by M. D. Anderson and as a sample given to an NCI researcher by the cancer center. “The mix-up with melanoma cell line M14 likely happened early in the history of the cell line,” NCI says on its Web site.

    Although the NCI-60 panel's Web site now details the history behind its “mischaracterized” cell lines—Daniel Zaharevitz, chief of the information technology branch at NCI's Developmental Therapeutics Program, considers that description more accurate than contaminated or misidentified—the institute hasn't gone out of its way to inform researchers who obtained these lines in the past that the lines are now suspect. Zaharevitz says the agency is wary of creating undue concern, because much of the work with such lines, such as drug testing, is unlikely to have been compromised.

    Liscovitch feels that greater exposure of the problem is needed. He publicized the story of MCF-7/AdrR, now known as NCI-ADR/RES, in the 8 January Cancer Letters. There may be more such stories in the future. There is some evidence that the NCI-60 panel's version of the colon cancer cell line HCT-15 is not the same as the original line.


    A Lonely Crusade

    1. Rhitu Chatterjee*
    1. Rhitu Chatterjee is a science writer in Washington, D.C.

    Walter Nelson-Rees drew hostility for exposing cell-line contamination, but his work is now being taken up by others.


    In 1951, a 31-year-old African-American woman was admitted to Johns Hopkins Hospital in Baltimore, Maryland, for treatment for cervical cancer. The hospital sent a sample of her cancerous tissue to Hopkins tissue culture expert George Gey, who successfully cultured it in his lab. Henrietta Lacks's ferocious cancer cells spread throughout her body and eventually killed her. And her immortalized cells, named HeLa cells after her, quickly spread through labs across the world—and not always because researchers had requested a sample for study.

    In 1966, Stanley Gartler of the American Type Culture Collection found that 18 of the first 20 human cell lines established were chromosomally and biochemically identical to HeLa cells. All 18 lines were known to have come from Caucasian individuals. Yet Gartler found that each had a genetic variant of an enzyme found only in the small percentage of African-American population that Lacks had belonged to. Gartler published his findings in Nature in 1968, marking the first reported case of HeLa contamination. It was only the beginning.


    HeLa cells came from Henrietta Lacks's cervical cancer.


    A few years later, Walter Nelson-Rees began discovering contaminations in lines from laboratories across the world. At the time, he was at the Cell Culture Laboratory of the University of California, Berkeley, at Oakland, characterizing, storing, and distributing cell lines for the U.S. National Cancer Institute (NCI). Over more than 10 years, he counted 279 contaminated lines from 45 different laboratories. Many were contaminated with cells from other species, but the bulk—more than 40 individual lines—had been overcome by HeLa cells. “This sort of scenario happened many, many times; people who thought they were working with one type of cells [were later found to be] working with HeLa cells,” he says.

    Nelson-Rees published his results in a series of papers in Science in the 1970s, urging scientists to stop using contaminated cell lines, re-evaluate their previous research, and employ simple quality-control practices such as regularly verifying their lines' authenticity.

    Nelson-Rees's revelations threw the community into a frenzy. Many studies were called into question, and Nelson-Rees was naming names. Some biologists reacted with hostility, and Nature in an editorial called Nelson-Rees a “self-appointed vigilante.” In a 2001 commentary on cell line authentication, Stephen O'Brien of NCI in Bethesda, Maryland, who had worked with Nelson-Rees, recalled the tension: “Human emotions were on edge, red faces were appearing in the most prestigious laboratories, and discussions of the problem lost any semblance of civility.” Nelson-Rees even remembers an anonymous telegram offering to send him a one-way ticket to South Africa. “My aim was to clear up a morass of contamination, and it wasn't easy,” he says.

    The attacks ultimately took their toll. In 1981, Nelson-Rees quit science and opened an art gallery in San Francisco.

    HeLa continues to spread today. In 2004, Gertrude Buehring of the University of California, Berkeley, and her colleagues surveyed 485 researchers from 48 countries who were working with specific cell lines and found that 49 were using seven lines that others had shown to be contaminated by HeLa. When Buehring conducted a PubMed search to identify the number of publications from researchers wrongly using HeLa-contaminated lines as though they still had cells of the original line, she found a total of 220 papers between 1969 and April 2004. And the number of publications on research using cell lines shown to have become contaminated by HeLa had increased by a factor of 10 between 1969 and 2004, whereas the total number of publications had increased by only a factor of 2.7.

    But perhaps Nelson-Rees will finally get his due. Other scientists are now taking up his fight against cell line contamination (see main text). And in 2004, the Society for In Vitro Biology publicly recognized his contribution to science with a lifetime achievement award.


    A Half-Century Late, Alternative Accelerator Takes Off

    1. Edwin Cartlidge*
    1. Edwin Cartlidge is news editor of Physics World magazine in Bristol, U.K.

    It's not quite a cyclotron and not really a synchrotron, but the fixed-field alternating-gradient synchrotron could create a whole new role for particle beams

    Long time coming.

    This 5-meter-radius FFAG built at the KEK laboratory in Japan outperforms traditional synchrotrons.


    When physicists started developing particle accelerators known as fixed-field alternating-gradient synchrotrons (FFAGs), Dwight Eisenhower was president of the United States, and Elvis Presley was a promising unknown. Now, 50 years later, researchers are starting to build FFAGs that really work. Proponents say these accelerators may bring particle beams to bear on new fields and applications: destroying tumors with pinpoint precision, slashing the half-life of radioactive waste, and teasing out the properties of the most fundamental particles of matter. “FFAGs could revolutionize accelerator-driven science in general,” says Robert Cywinski, an experimental physicist at Leeds University in the U.K. “Every university should have one.”

    Like the synchrotrons and cyclotrons familiar to today's scientists, FFAGs use electric fields to accelerate bunches of charged particles such as protons or electrons around a ring at close to the speed of light. But they differ in the way they guide the particles around the circuit. In cyclotrons, a fixed magnetic field forces a beam of charged particles to move in a circle, but regular voltage “kicks” boost the particles' speed and make them spiral outward. The size of the huge magnets needed to keep the particles inside the machine limits the energy of the beam.

    Synchrotrons overcome that problem by using variable magnetic fields that ramp up as the particles increase in energy. But once the field is geared up for high-energy particles, you cannot inject more, low-energy particles into the accelerator. That cutoff puts a ceiling on the beam's intensity.

    FFAGs solve those problems by using a magnetic field that stays fixed in time but that grows stronger toward the outside of the ring. As particles gain energy and drift outward, the strong field keeps them on track. As a result, particles with a range of energies can all orbit at the same time, enabling FFAGs to produce particle beams more energetic than a cyclotron's and more intense than a synchrotron's.

    The idea was originally put forward by Japanese physicist Chihiro Ohkawa in 1953. Researchers in the United States built three small FFAGs in the late 1950s and early 1960s. But the difficulty of creating the carefully shaped magnetic fields made larger devices impractical.

    However, better magnets and computer simulations of three-dimensional magnetic fields have renewed interest in FFAGs. The spur came in the late 1990s from plans to build a neutrino factory, a multibillion-dollar facility that would produce extremely intense and high-energy beams of neutrinos. Yoshiharu Mori and colleagues at the KEK particle physics lab near Tokyo thought that an FFAG would be ideal for accelerating particles needed to create the neutrinos. In 2000, they built a small “proof of principle” device and have since constructed a larger machine with a radius of about 5 meters. Last year, this machine accelerated protons up to 100 million electron volts at a rate of 100 bunches a second—twice the maximum rate attained with a synchrotron.

    This prototype machine was designed to test applications such as hadron therapy, which uses protons and other charged particles to destroy tumors. Mori has also joined Kaichiro Mishima and colleagues at Kyoto University to test whether an FFAG proton beam can slash the half-life—and therefore the threat to future generations—of some long-lived radioactive waste. Other attempts at “transmutation” of nuclear waste involve using linear accelerators, but Mishima thinks FFAGs have the edge because they are cheaper, smaller, and more efficient. “Whereas a linear accelerator would need to be up to a kilometer long, an FFAG would probably be just a few tens of meters in diameter,” he says.

    First, however, FFAGs must clear some major technical hurdles. KEK has so far concentrated on “scaling” FFAGs, in which the orbits of the particles remain a constant shape as the size of these orbits increases, or “scales,” with momentum. But these require large magnets and are extremely complex. Much simpler and more compact, theorists say, would be a “nonscaling” FFAG, in which particle orbits change shape with increasing energy. No one has built one yet, because it has been assumed that the shape-shifting orbits make the beam almost impossible to confine. But a new U.K.-led consortium of universities and radiation oncology centers believes it can solve that problem by circulating particles so quickly that the beam will not have time to spread significantly.

    The consortium recently received $16 million to build a small demonstration nonscaling electron FFAG, known as EMMA, at the U.K. government's Daresbury Laboratory and design a proton device for hadron therapy. “There's an element of risk involved,” says Roger Barlow of the University of Manchester, who leads the U.K. project. “But I'm confident it will work. It's a question of how hard it will be to get EMMA up and running.” Meanwhile, physicists at Brookhaven National Laboratory in Upton, New York, working with researchers from industry, hope to get funding to build their own nonscaling device.

    If all goes as planned, a nonscaling FFAG could be treating patients at a British hospital within 6 or 7 years, says consortium member Bleddyn Jones, a cancer specialist at University Hospital Birmingham.


    Saving a Lost Culture's Megalithic Jars

    1. Richard Stone

    Iconic and baffling, massive stone urns scattered across Laos may hold clues to the rise of Southeast Asia's first citiesXIENG KHOUANG, LAOS—You could easily insert a full-grown adult into any of the dozens of huge gray jars strewn across a windswept promontory in central Laos. Or a husband and wife, for that matter, or several small children. The hallowed corpse of a king, or shrieking prisoners captured in battle: The gruesome possibilities are endless. Although the origins of the prehistoric sandstone vessels are hazy, divining their purpose requires minimal, albeit morbid, imagination. “All around these jars are graves,” says Julie Van Den Bergh, UNESCO archaeologist for the Plain of Jars. She and other experts speculate that bodies were put in the jars to decompose, and then the remains were scooped out for burial.

    The world's biggest mortuary vessels, some upright and some tipped over in scraggly grass parched brown in the winter dry season, “are a spectacular enigma,” says Peter Bellwood, an archaeologist at Australian National University in Canberra. For starters, no one knows which culture they belong to. Their utter lack of adornment has cloaked them in mystery. The urns presumably were hewn from nearby quarries, but radiocarbon dating is all over the map. So is their location: There are nearly 2500 jars, lids, and stone disks at 52 known sites on the Plain of Jars, defined as the diamond-shaped, 15,000-square-kilometer Xieng Khouang Province.

    A concerted effort is now under way to save one of Asia's enduring archaeological riddles. UNESCO and the Laos government have just launched a new phase of a program to safeguard the Plain of Jars before its nomination, anticipated in 2008, for the U.N. agency's World Heritage List. One task is to protect the Xieng Khouang Plateau from an expected onslaught of tourists. Another is to protect the tourists themselves from unexploded ordnance (UXO) that claims dozens of victims in the countryside each year, a legacy of the U.S. “Secret War” waged here in the 1960s and early '70s.


    Deciphering the meaning of the jars “could shed light on the relationship between increasing social complexity and megalith construction,” says paleoanthropologist Russell L. Ciochon, a Southeast Asia specialist at the University of Iowa, Iowa City, who compares the jars to other enchanting and better-known megaliths: Britain's Stonehenge and the Moai faces of Rapa Nui (Easter Island). Tracing the jars' provenance, Ciochon adds, “would offer valuable insight into social organization in prehistoric Southeast Asia” during its transformation from a loose collection of subsistence farming communities to a web of urban centers that traded with China and India and also imported their religions, Buddhism and Hinduism.

    Drained of lifeblood

    According to local lore, the jars were made to store lau-lao, or rice whiskey, for a feast 1500 years ago to celebrate the military victory of King Khun Chuang over an unruly chieftain, Chao Angka. In the 1930s, Madeleine Colani, a French archaeologist, pieced together a more macabre story. Near the town of Phonsavan in Xieng Khouang, at Thong Hai Hin (also called Ban Ang or Site One), one of the bigger fields with more than 250 urns, Colani unearthed grave goods including glass and carnelian beads, ceramic potsherds, bronze bracelets, and spearheads. The artifacts resemble those from Iron Age sites in northeastern Thailand, says Charles Higham, an archaeologist at the University of Otago in Dunedin, New Zealand, who is excavating a Thai site from that period. Higham pegs the Laos grave goods to the 2nd to 5th centuries C.E.

    Colani also found charred bone and ash in a nearby cave in a limestone hill. In a 600-page treatise on the Plain of Jars, she ventured that remains were cremated in the cave, which has a meter-wide hole in its ceiling—a natural chimney. Ash and bone were then interred in the jars, while tools, jewelry, and other objects for use of the deceased in the afterlife were buried next to the jars, Colani proposed. Stone disks served as grave markers.

    Before colleagues could probe this theory, Laos descended into conflict. After 3 decades of internal strife, the war in Vietnam spilled over the border in the 1960s. Central Laos bore the brunt of U.S.-backed carpet bombing—in all, some 2 million tons of munitions—to disrupt North Vietnamese supply lines. “It's a miracle that so many jars survived,” Van Den Bergh says.

    Not surprisingly, study of the jars languished. Things picked up again in 1994, when Thongsa Sayavongkhamdy, now director of Laos's Department of Museums and Archaeology, excavated several burials near the jars. His work supported Colani's view of the jar fields as cemeteries. But the bone fragments he uncovered were not charred. “Was Colani right; did they really cremate the dead? We're not sure,” says Bellwood. Intriguingly, even today villagers erect small stupa containing ash of deceased relatives near the jars.

    UNESCO's working hypothesis is that bodies were placed in the jars to rot and dry out: a ritual decomposition, or, as Van Den Bergh calls it, “distilling the body of its human essence.” (Lids found at other sites would have kept out scavengers.) She cites a compelling modern parallel: Cambodian, Lao, and Thai nobility for centuries have been interred in large urns before cremation. An official at Thailand's Royal Palace told Science that each previous king of the present dynasty, upon his death, has been placed in a sitting position in a large golden urn for 3 months before cremation. But hard evidence for such a practice in ancient Laos is elusive. “Whether bodies were distilled in the jars is probably unknowable,” says Higham.

    The Asian megalith makers too are inscrutable. Colani speculated that the jars were fashioned by a vigorous society that mined salt, a valuable commodity, and was situated favorably on caravan routes. Similar large stone jars have turned up in the Assam Province of northeastern India, suggesting a possible cultural connection. However, Van Den Bergh notes, no one has yet pinpointed a prehistoric settlement in Xieng Khouang.

    The age of the jars is anyone's guess. Charcoal found just under some of them is 4000 years old, and bone fragments from a few burials are 900 to 1000 years old. The bulk of material is between 2500 and 1500 years old. Although there is no way to directly date the sandstone jars, Ciochon suggests using optically stimulated luminescence to date quartz crystals in sediments underneath. In this recent technique, light liberates trapped electrons from long-buried crystals; intensity depends on background radioactivity and duration of burial. For the quartz trapped directly beneath upright jars, “the last time these sediments were exposed to light was when the jars were put in place,” Ciochon says. UNESCO hopes to find funding for such dating, Van Den Bergh says.

    It's evident that the steely gray jars in Xieng Khouang were hewn from local rock. When first chiseled, they would have been white or cream-colored and sparkled in the sun, says Van Den Bergh. “They must have been stunning,” she says. In 2000, in highlands near Site Three, Thongsa documented the vestiges of a jar factory: unfinished vessels near an ancient sandstone quarry. The jars presumably were rolled on logs and perhaps ferried by boat part way, “then finished at the site,” says Van Den Bergh. But there were no clues to the artisans' identities. Nor do the urns give much away. Of the roughly 2000 verified jars, just one has an image inscribed by its makers: Excavating at Thong Hai Hin in November 1994, Eiji Nitta, an archaeologist at Kagoshima University in Japan, uncovered a faded bas relief image of the upper body of a human figure with upturned arms near the base of a jar. “They are very functional,” says Van Den Bergh. “Whoever made them didn't put any creativity into it.”

    A handful of lids and disks have images of tigers and monkeys, and one disk at Site Two is adorned with a curious carving of a froglike creature. Large stone jars on central Sulawesi Island in Indonesia “also have animals on the lids,” says Bellwood. But there is no other evidence linking the two sites.

    Bellwood believes that archaeology alone will not unmask the jar people. But comparative linguistics might. Presuming that the makers of the Sulawesi jars spoke an Austronesian language, he argues, those in Laos might have been an Austronesian enclave—perhaps from central Vietnam, where the Sa Huynh culture used burial pots some 2000 years ago. But Bellwood acknowledges that he has not been able to find any “linguistic descendents or identifiable place names in Laos today.”

    Scientific minefield

    With plenty of puzzles left to solve, UNESCO and Laos authorities are endeavoring to keep Xieng Khouang's treasures intact—both for future study and to attract more tourism revenue to the impoverished province. Van Den Bergh's team has mapped the Xieng Khouang sites and is helping officials craft a management plan for the Plain of Jars. A new fence at Site Three is keeping out cattle, which had trod circles around jars, rubbing against them and compressing the soil so much that some jars subsided. Before UNESCO and Laos officials intervened, some jars had been cut to serve as troughs for feeding animals or collecting drinking water, while lids and disks became millstones. And during the Secret War, untold numbers of relics were blown to bits.

    The scars of war are still plain to see. Thong Hai Hin and surrounding fields, studded with spiky wild aloe, are pockmarked with bomb craters a few meters deep and several meters across. The nonprofit Mines Advisory Group has cleared 175 UXO—including bombs, rockets, artillery shells, mortars, and 20-millimeter antiaircraft rounds—from around the jars and paths at the three main Xieng Khouang sites. Van Den Bergh has ensured that artifacts are not damaged during clearance, rescuing a dozen stone tools, pottery, iron knives, and bone fragments.

    Although UXO make the surrounding countryside treacherous, the Xieng Khouang sites are becoming safer for research. That has emboldened Van Den Bergh to hunt for a partner on a ground-penetrating radar survey. Farther afield, newly identified jar sites near the capital, Vientiane, and the medieval city of Luang Prabang are wholly unexplored. If that's not enticement enough for archaeologists, the jars continue to defy analysis. When Van Den Bergh first arrived here 6 years ago, she admits, “I didn't know much about the jars. But there wasn't much to know.” And there still isn't.