News this Week

Science  06 Nov 2009:
Vol. 326, Issue 5954, pp. 778
  1. Physics

    Helium-3 Shortage Could Put Freeze On Low-Temperature Research

    1. Adrian Cho

    The weird effects of quantum mechanics often emerge at extremely low temperatures. So 3 years ago, Moty Heiblum, a physicist at the Weizmann Institute of Science in Rehovot, Israel, ordered a large “dilution refrigerator,” which uses frigid liquid helium as a coolant and can chill tiny electronic devices to within a thousandth of a degree of absolute zero, or 1 millikelvin. But now the manufacturer, Leiden Cryogenics B.V. in the Netherlands, cannot deliver the completed fridge: It cannot get enough helium-3—100 liters of room-temperature gas, as it's sold on the market—to fill the rig.

    Heiblum has fallen victim to a severe shortage of helium-3, the lighter isotope of the most inert element. Two weeks ago, he also lost about 15 liters of helium-3 from an existing fridge when an electronic valve failed. When Heiblum tried to buy more, a supplier in the United States turned him away and a European company wanted an unaffordable €1300 per liter, up from €100 just 2 years ago. “If this continues, then low-temperature physics will just disappear,” Heiblum says.

    No end to the shortage is in sight, however. In recent years the supply of helium-3 has dwindled, while the demand has skyrocketed—especially since 2002, when the U.S. Department of Homeland Security (DHS) and Department of Energy (DOE) began deploying thousands of helium-3–filled neutron detectors to help prevent the smuggling of plutonium and other radioactive materials into the country. In the short term, demand will likely top 65,000 liters per year, while supply will hover between 10,000 and 20,000 liters per year, according to a DOE study. The shortfall threatens several research fields, and DOE, the major supplier, is releasing the gas only to researchers with U.S. funding.

    Global warming.

    Around the world, physicists like Moty Heiblum in Rehovot, Israel, say they cannot get the helium-3 they need to reach ultralow temperatures. Security programs in the United States have soaked up 85% of the supply.

    CREDITS (TOP TO BOTTOM): COURTESY OF THE WEIZMANN INSTITUTE OF SCIENCE; SOURCE: DOE

    Helium-3 also fills neutron detectors at large neutron-scattering facilities used to probe materials, such as the one at the new Japan Proton Accelerator Research Complex (J-PARC) in Tokai. The projected need for that application alone exceeds 100,000 liters over the next 6 years. J-PARC researchers need 16,000 liters of helium-3 to complete detectors for 15 of 23 beamlines, says J-PARC's Masatoshi Arai: “If we cannot get helium-3 and detectors, … [then] we cannot perform sufficiently good experiments from the neutron facility at J-PARC, for which we spent $1.5 billion for construction.”

    Low-temperature physicists say they need between 2500 and 4500 liters of helium-3 per year, primarily to fill new dilution refrigerators. Helium is the only substance that remains liquid at absolute zero, and only by pumping the vapor off a liquefied mixture of helium-3 and heavier helium-4 can physicists achieve steady temperatures below 0.8 kelvin, says William Halperin, a physicist at Northwestern University in Evanston, Illinois. “If we lose our helium-3 [supply], we're totally screwed,” says Halperin, who notes that work on quantum computing and nanoscience often requires extremely low temperatures.

    Helium-3 also serves a role in medical imaging. When inhaled by a patient, it allows researchers to image the lungs with an MRI.

    The helium-3 supply likely won't return to its former levels. Rare in nature, the gas comes mainly from the radioactive decay of tritium generated in nuclear reactors. Pure tritium is an ingredient in hydrogen bombs, so for decades the United States and the Soviet Union kept large reserves of it and sold the helium-3 skimmed from it. But after the Cold War ended, the United States and Russia reduced their tritium reserves. Prior to 2009, DOE released 60,000 liters of helium-3 annually. In fiscal year 2009, it released 35,000 liters. Russia releases a few thousand liters annually, and Canada has accumulated tritium from civilian reactors that, if purified, could provide a one-time boost of 80,000 liters of helium-3 and several thousand liters per year thereafter, DOE estimates.

    To ease demand, researchers are looking for alternatives to helium-3, especially for neutron detectors for security. Within a sealed tube of gas, a helium-3 nucleus can absorb a passing neutron and then split into charged fragments that create a detectable electrical signal. Several alternative technologies exist, such as tubes filled with boron trifluoride gas or glass fibers that emit light when struck by a neutron. None of them is a “one-to-one replacement” for the helium-filled tubes in terms of sensitivity, specificity, and ease of use, says Daniel Stephens, a nuclear engineer at Pacific Northwest National Laboratory in Richland, Washington. But as the projected demand for helium-3 for security alone outstrips the U.S. supply, DHS and DOE will likely begin to deploy other technologies soon, he says.

    Meanwhile, an interagency working group convened by the White House has set three principles to guide the distribution of helium-3, says Steve Fetter, assistant director at-large at the White House's Office of Science and Technology Policy. DOE, which controls the U.S. supply, would give priority to uses for which helium-3 is irreplaceable, restrict its use to security applications in which it offers a decisive advantage, and give priority to projects in which the United States already has a substantial investment, Fetter says.

    That approach should ensure a supply for science. But it shuts out overseas researchers. Fetter says that “non-U.S. requests are not excluded from consideration.” However, DOE brings helium-3 to market through Spectra Gases Inc. in Branchburg, New Jersey. In a 6 October e-mail message to a would-be buyer, Spectra Vice President Jack Faught said that DOE must approve sales of recently released helium-3 and that it “is reserved for research projects that are funded by certain specific agencies of the United States Government.” Spectra did not reply to requests for comment.

    That means scientists overseas cannot start new projects and equipment manufacturers may go out of business. “We only make dilution refrigerators,” says Giorgio Frossati, co-founder of Leiden, one of three leading manufacturers of the devices. “If the helium-3 supply stops, it means that we have to close down.” Under current conditions, Frossati says, the company, which employs 10 people and has annual receipts of €5 million, can hang on for a year.

    Even if the current crunch can be ameliorated, the price of helium-3 will likely never return to the traditional $100 to $200 per liter. So certain types of research may become much more expensive. Meanwhile, reserves of helium-4 may be exhausted within decades, an even bigger problem that the National Academy of Sciences will weigh in on soon.

  2. U.S. Science Policy

    Peer Review Not Popular at Homeland Security

    1. Yudhijit Bhattacharjee

    When it comes to funding basic research at the Department of Homeland Security (DHS), program officers seem to rely mostly on their own opinion. An analysis of the agency's $1 billion science and technology directorate has found that only about 40% of the $175 million spent on basic science was awarded through a competitive process. And only a portion of that slice is subject to outside peer review.

    “That's not good for DHS and not good for science,” says Cindy Williams, a political scientist at the Massachusetts Institute of Technology in Cambridge who chaired a study by the National Academy of Public Administration (NAPA) released earlier this year. Williams testified last week before the technology panel of the House of Representatives science committee at a hearing that looked at how DHS could do a better job of using science and technology. She recommended that the science directorate follow the example of the National Science Foundation and other agencies that award funds “on a competitive basis based on scientific peer review except in cases when that is clearly not feasible.”

    Asked at the hearing if DHS planned to follow that advice, Bradley Buswell, acting under secretary of the science directorate, was non-committal. “I agree that competition is good and that peer review is one means of assuring that we are selecting high-quality projects,” said Buswell. He noted that some DHS-funded research projects, including proposals funded through the agency's university-based Centers of Excellence program, follow this model. But he said that DHS's practice of reviewing research proposals internally was no less rigorous.

    The NAPA study found that 31% of DHS's basic research funding last year went to universities. Even so, says Williams, “there is no peer review for individual projects funded by the centers” with money from their DHS award. Almost none of the remaining funds, divided among industry, federal labs, and other entities, was awarded after external peer review, Williams says.

    Peerless.

    A study led by Cindy Williams found that peer review is used infrequently by DHS to fund basic research.

    CREDITS: COURTESY OF THE MIT CENTER FOR INTERNATIONAL STUDIES; (INSET) NAPA

    Williams says directorate officials told her there were “only a few performers” who could meet the agency's needs. They also said few universities had the secure facilities needed to carry out classified research projects, although Williams notes that the bulk of the basic research funded by DHS is unclassified.

    DHS's avoidance of outside advice is unusual even among security-conscious agencies. The Department of Defense uses peer review to disburse much of its $1.5 billion basic research budget. And in recent years, U.S. intelligence agencies have tried to tap the research community by soliciting proposals and setting up external peer-review panels.

    “We are a strong supporter of peer review,” says Barry Toiv of the Association of American Universities. “It is probably a good idea for agencies to receive outside advice as they allocate their research funding.”

  3. Stem Cells

    CIRM Awards Seek to Move Cell Therapies to the Clinic

    1. Jocelyn Kaiser
    In the mix.

    Only a few of CIRM's disease teams will use human embryonic stem cells like the colony here (light blue).

    CREDIT: CIRM

    Five years after it launched, the California Institute for Regenerative Medicine (CIRM) last week awarded its first disease-oriented grants—$230 million to 14 teams—intended to speed stem cell therapies to patients. In seeming contrast to its original mission, only about one-third of the 4-year grants involve research using embryonic stem (ES) cells. The state created CIRM largely to fund ES cell research, which was lagging because of Bush-era restrictions on the controversial technology.

    CIRM officials were quick to say that they never intended to fund only work on embryonic cells. Although “it is a priority to fill that gap,” said CIRM board chair Robert Klein at a press conference, “our commitment to the voters … is that we would pursue the very best cell type for each disease.” CIRM President Alan Trounson proclaimed the mix of embryonic, adult, and cancer stem cell types funded “about the right proportion.”

    To date, CIRM has funded basic research, infrastructure, and training; these awards are the first to support the preclinical work needed to bring a lab discovery to the point at which it's ready to be tested in patients. The goal of each “disease team” is to file a new drug application with the U.S. Food and Drug Administration within 4 years—much faster than the usual decade or more. CIRM has been shifting focus partly in response to the Obama Administration order earlier this year that lifted restrictions on using federal funds to study human ES cells (Science, 27 March, p. 1660).

    The 14 projects include four using human ES cells to treat stroke, type 1 diabetes, macular degeneration, and Lou Gehrig's disease; a fifth project is using an alternative to embryonic cells, induced pluripotent stem cells, for a skin disease. Other teams are using adult stem cells—sometimes combined with gene therapy—to treat diseases such as brain cancer, heart disease, and HIV/AIDS. Three grants will target cancer stem cells. The one award to a biotech company, $20 million to Novocell Inc. in San Diego, for the diabetes team, is actually a loan.

    Donald Kohn of the University of California, Los Angeles (UCLA), who heads a $9 million project using gene therapy to treat sickle cell disease, says the awards are important because the money will support the entire range of expertise needed to move a therapy into clinical trials, including regulatory staff. The three CIRM grants to UCLA “will make [the research] go a lot quicker,” said Kohn in the press conference.

    Arnold Kriegstein of the University of California, San Francisco, who has worried that CIRM is pushing too hard to move stem cells into the clinic, is encouraged by the focus on both embryonic and adult stem cells, which are further along. But he still worries about CIRM's “shift towards higher risk preclinical studies at the expense of the huge amount of basic research that needs to be done.”

    At the same time, the National Institutes of Health (NIH) is moving closer to funding its first grants under expanded federal guidelines on ES cells issued on 7 July. The holdup is that NIH hasn't decided which lines are eligible for funding.

    NIH has received submissions from seven institutions seeking approval for 91 cell lines and is “moving expeditiously” to see if the lines meet the spirit of new ethical rules, an NIH official says. A working group of the NIH director's advisory committee will submit recommendations to the full committee in December, which will then send its advice to NIH Director Francis Collins. Those lines derived from embryos donated since 7 July in accordance with the new guidelines may be approved sooner, the NIH official says.

  4. Privacy

    Court Orders Stanford Expert to Surrender Manuscript

    1. Sam Kean

    A Stanford University professor is fighting to keep his unpublished book manuscript out of the hands of tobacco company R.J. Reynolds (RJR), which subpoenaed it after he testified as an expert witness for smokers who are suing the company. Last month, Stanford asked the court to reject the company's demand, saying that it could have a “chilling effect” on researchers serving as expert witnesses.

    Scholars are often shocked and upset that their unpublished work is subject to subpoena, says Joe Cecil, senior researcher at the Federal Judicial Center in Washington, D.C., a government educational and research agency. But, especially if researchers offer themselves as expert witnesses, courts have wide-ranging powers to collect evidence. He adds, “Even though these kinds of cases have been around for decades, the scientific community doesn't really have an organized response.”

    Stanford medical historian Robert Proctor plans to serve as an expert witness—either in person or via taped testimony—for smokers in many of the 8000 or so cases they are bringing against tobacco companies in Florida. (For technical reasons, a state judge threw out a class-action lawsuit by Florida smokers a few years ago, so plaintiffs resorted to individual suits.)

    Proctor has become a popular witness because of his expertise on the history of tobacco in the United States and because of his provocative criticisms. He calls tobacco companies the biggest environmental polluters on the planet and claims that “the cigarette is the most carefully designed artifact in the history of civilization, with the possible exception of nuclear bomb cores.” Since December, tobacco companies have lost seven of the nine cases tried in Florida, some of which included Proctor as a witness, for an average of a few million dollars each time. All the decisions are pending appeal.

    Proctor has also been writing an 800-page book titled The Golden Holocaust: How cigarette makers engineered a global health catastrophe. The manuscript, which he hopes to finish early next year, so far consists largely of Proctor's private jottings and notes, he says. He plans a wide-ranging account of the tactics tobacco companies used to sell cigarettes, including his views on how tobacco companies used science as a rhetorical tool. Much of Proctor's research comes from scientific studies and other documents in the tobacco companies' own files, which were secured by plaintiffs in anti-tobacco litigation and posted online.

    Standoff.

    Robert Proctor has refused a tobacco company's demand for his unpublished research.

    CREDIT: LINDA A. CICERO/STANFORD NEWS SERVICE

    “Companies linked themselves with an open-research ideology: ‘Let's keep our minds open to the possibility that smoking doesn't cause cancer,’” Proctor says. “It was a brilliant system that captured a lot of academics.” Companies sponsored millions of dollars of research as well into alternative explanations for cancer, he says, including mites, viruses, baldness, and month of birth.

    RJR asked William Parsons, a circuit judge in Florida's Volusia County, to issue a subpoena for The Golden Holocaust. “When you become a paid expert witness, your notes, your correspondence with other people become available,” says Theodore Grossman, a partner at the law firm representing RJR, Jones Day in Cleveland, Ohio. “They're needed in order to conduct an effective cross-examination.” Adds Cecil, “Frankly, if [Proctor is] willing to take on the role of an expert who's compensated, … he's consented to a much more searching inquiry.” But Proctor has been fighting the subpoena since August.

    A request for unpublished scientific research is unusual but not unprecedented. In recent years, scientists who study lead paint, drugs, and toxic chemicals have received subpoenas for raw data in tort cases. Some capitulated, and a few left academe after bad experiences. At times, companies have even subpoenaed peer reviewers of scientific manuscripts. Proctor's case differs from most in that he conducted no independent experiments, just analyzed tobacco companies' own work.

    In an amicus curiae brief filed on 8 October with the Florida court to support Proctor, Stanford's dean of research, Ann Arvin, urged that the subpoena be dropped: “Stanford respectfully urges the Court to consider the broad societal interest that academic researchers not be forced to pre-publish their uncompleted research,” which could harm their professional standing.

    Grossman argues that courts have effective rules to prevent the dissemination of unpublished work. “If Proctor had approached us to get a confidentiality seal, I'm sure we could have worked something out. He didn't. … Proctor apparently does not trust the rules of the courtroom.”

    Proctor scoffs at RJR's claim that tobacco companies need more evidence about his views. He remains adamant that he will not surrender the bulk of his unedited, unfiltered manuscript, which he says would violate his privacy and First Amendment rights. The issue will likely be resolved over the next few weeks.

  5. ScienceNOW.org

    From Science's Online Daily News Site

    CREDIT: GARETH JONES

    A Little Fellatio Goes a Long Way Oral sex is surprisingly rare in the animal kingdom. Humans do it, of course, as do bonobos, our close relatives. But now researchers have observed the practice for the first time in a nonprimate. During intercourse, female short-nosed fruit bats lick the genitals of their partner, a possible ploy to increase copulation time. The discovery suggests that there may be a biological advantage to fellatio.

    A Body Count for Two Man-Eating Lions For 9 months in 1898, two lions terrorized the southern Kenyan region of Tsavo, killing as many as 135 people by one account. Although the almost mythic tale has spawned three movies, people still debate the final death toll. Now, hair and bone samples from the famed creatures have shed light on how many people they devoured and why they did it.

    Did Ancient Earth Go Nuclear? A surge of oxygen littered early Earth with millions of tiny nuclear reactors, blasting ancient life with radiation. That's the scenario a team of researchers has proposed to account for the disappearance of a radioactive mineral from the geological record. If true, this primordial nuclear age could have played a role in the evolution of early life forms.

    A Concise and Precise Definition of P-Value Victor De Gruttola, the chair of biostatistics at the Harvard School of Public Health, is passionate about his p-values. But journalists, he says, often get the concept wrong. To heal wounds and improve communications between biostatisticians and the confused masses that rely on them, De Gruttola agreed to discuss the details of what a p-value means and does not mean with ScienceNOW.

    Read the full postings, comments, and more on sciencenow.sciencemag.org.

  6. Swine Flu Pandemic

    Developing Countries to Get Some H1N1 Vaccine—But When?

    1. Martin Enserink
    Priorities.

    U.S. lacks enough vaccine to meet demand, as crowds in Maryland found out on 21 October.

    CREDIT: AFP/GETTY IMAGES/NEWSCOM

    When Margaret Chan addressed the United Nations General Assembly on 4 May, just weeks after swine flu had surfaced, she ended on a solemn note. “An influenza pandemic is a global event that calls for global solidarity,” the director-general of the World Health Organization (WHO) said. “It is my job to do whatever is possible to ensure that developing countries are not left without protection.”

    Six months later, many global health experts conclude that, despite all her hard work, Chan has precious little to show for it. WHO has said that about a month from now, it will begin supplying developing countries with H1N1 vaccine donated by manufacturers and rich countries. But it has secured only about 200 million doses for 95 countries that together are home to a third of the world's population. Compare that with the 250 million doses that the United States has purchased, Germany's 50 million, or France's 94 million, and “global solidarity” aren't the first words that come to mind. Moreover, much of that vaccine won't arrive for several months, and the pandemic marches on.

    “It's probably going to be too little, too late,” says David Fidler, an international law professor at Indiana University, Bloomington, and an expert on global health security. Tido von Schoen-Angerer, who directs the Campaign for Access to Essential Medicines for Doctors Without Borders (MSF) in Geneva, calls WHO's operation “largely symbolic.” Years of debate and negotiations have failed to produce a system to ensure equal access to the lifesaving vaccines, he says, leaving WHO to distribute mere table crumbs. The only good news, he adds, is that the pandemic is relatively mild.

    A month before its scheduled start, many details of WHO's operation are still lacking. The agency won't make public the list of eligible countries, says Marie-Paule Kieny, director of the WHO Initiative for Vaccine Research, because some of the 95 may opt out of the plan. In fact, only about 40 countries so far have formally indicated to WHO that they want the vaccine, she says. Some have qualms about the fact that they have to assume liability for adverse events—a condition that the vaccine manufacturers have also imposed on rich countries. “This is creating a lot of discussion,” says Kieny. “Governments want to know what it means and whether the vaccine is safe.”

    There are uncertainties on the supply side as well. Two big vaccine manufacturers, Glaxo-SmithKline (GSK) and Sanofi Pasteur, have pledged 50 million and 100 million doses, respectively, whereas two smaller players, MedImmune and CSL, will each pitch in 3 million doses. The size of the donation from the 10 individual countries that have promised to support WHO remains unclear, however. Some, such as the United States and Australia, have said they will donate 10% of their own supply, but others have not made a firm commitment. Some may donate money instead, Kieny says: “We have to see who is going to do what.”

    It's also unclear when the pledged vaccine will materialize. The timing is essential, given the fast-moving nature of the pandemic. Kieny says that GSK shipments will start in late November and last through April or May; Sanofi Pasteur has promised to start before the end of the year, she says. The U.S. government has made conflicting statements about when it will start providing its 25 million doses, but it's facing shortages itself and is under increasing political pressure to take care of its own population first. “It's going to be a very tricky decision-making process for any government,” says former Merck executive Adel Mahmoud, now a researcher at Princeton University.

    WHO expects that between late November and February, when most eligible countries in the Northern Hemisphere will be hit hardest, at least 37 million doses will be available for them, enough to vaccinate 2% of the population. That means the vaccine will at least have an impact among health care workers, the group a WHO panel has said should be first in line. But “there is still hope” that other risk groups can be protected in time as well, Kieny adds. In African countries that see few international travelers, the pandemic peak may come later, for instance, and in Southern Hemisphere countries, the vaccine may be useful during the second wave, expected to hit there in the first half of 2010. In any case, she says, “it's better than nothing.”

    Because the swine flu pandemic has been mild so far, the lack of access to the vaccine has not yet ignited the international political explosion some had feared. Developing countries have not stood up to demand vaccine, at least not in public, and not a single country has threatened to withhold H1N1 virus samples from WHO's global lab network until vaccine supply is guaranteed, as Indonesia did in the past with samples of the deadly H5N1 avian influenza virus. MSF and other nongovernmental organizations have remained mostly silent on the issue because it pales in comparison to the importance of access to AIDS and malaria drugs. The donations, although modest, probably helped to “let off some of the political steam,” says Fidler.

    But the world may not be so lucky next time—and few doubt that rich countries would have shown far less largess if the pandemic had been very severe. That's why it's important to increase the global production capacity for influenza vaccine and get rid of the antiquated production methods based on hens' eggs, Mahmoud says. One thing that might change the dynamic, says Fidler, is that new countries are entering the vaccine market. “China is now a big manufacturer,” he says. “India has scientific expertise. Brazil is becoming an important player. You may see some movement between the developing countries. We no longer have to rely on these difficult northsouth relationships.”

  7. Economic Recovery

    When Counting Jobs Isn't Enough

    1. Jeffrey Mervis

    Keeping track of the number of jobs created and saved by the $787 billion stimulus package is a staggering challenge for the Obama Administration. It's also extra work for grant recipients, who must report how they're spending the money and its impact on scientific employment.

    A federal pilot project launched this summer aims to increase the accuracy of the count and reduce the burden on U.S. research universities. If it succeeds, it could also lead to a better way of tracking how federal investments in science affect the country's long-term economic health.

    Last week, Administration officials reported that the initial $159 billion chunk of spending from the American Recovery and Reinvestment Act (ARRA) has created or saved 640,329 jobs. A small number of them are at universities and other institutions receiving part of the $20 billion slice of the recovery package flagged for research and science infrastructure projects. After filling out the first round of reports, due 30 September, university officials are exhausted—and frustrated.

    “I'm a vice president, and I personally completed every one of our 100-plus forms,” says Susan Sedwick, who oversees sponsored research at the University of Texas, Austin. “The guidelines are geared more to the construction industry and those receiving contracts than to the university environment,” she explains, noting differences in the definition of a job and how to count full-time equivalent positions. “My hat's off to OMB [the White House's Office of Management and Budget] for putting in a new system that did not crash. But we all need better guidance on what to do.”

    A summer surge.

    New student jobs led the hiring at one university in the sample, which added 119 jobs in July from all science awards. Of those, 10 were created by recovery funds.

    SOURCE: STAR PROJECT PRELIMINARY REPORT

    Clearing up those ambiguities is one of the goals of the Science and Technology for America's Recovery pilot project being run out of the White House Office of Science and Technology Policy (OSTP). Working with data from seven universities on all federal awards, the project has shown that it's possible to extract the information needed for ARRA from the numerous accounting systems already used by universities, says Julia Lane, a labor economist at the National Science Foundation who is coordinating the effort. The result is a more rigorous and accurate tally.

    “You don't ask the PIs [principal investigators], you follow the money,” Lane explains. “The finance department already has data on every award, and every pay period we know who's charged their time to that code. If they show up in the previous pay period, it's a job saved. If not, it's a job created. There's no argument—and it's completely auditable.”

    The next step is to scale up the system throughout the country to track ARRA spending, she says. OSTP Director and presidential science adviser John Holdren wants to go even further, to obtain a broader picture of what science can do for the country. In particular, Holdren would like to see the tracking system expanded to all awards, not just for ARRA-funded work, and combined with outcomes such as publications, patents, and spinoff companies. The result, Holdren says, would be to “increase the evidence base … on the cumulative impact of science investments on the nation's R&D work force and the role of science in [global] competitiveness.”

    Such a system would require the cooperation of researchers whose efforts are being tracked. That's already happening, says Michael Laskofski of George Mason University in Fairfax, Virginia, which is part of the pilot project. “One of the reasons I was interested in participating is that we're an emerging research university,” says Laskofski, noting that the school so far has received 21 ARRA awards. “And our faculty understand the importance to the nation of collecting this type of additional information.”

  8. ScienceInsider

    From the Science Policy Blog

    The National Institutes of Health (NIH) has decided to fund 840 of the more than 20,000 applications it received for its vaunted Challenge Grants program. That 4% success rate may be abysmal compared with the one-in-five rate for regular NIH grants, but it's more than twice as high as NIH's original projections.

    Critics of the Large Hadron Collider at CERN on the Switzerland-France border will petition the United Nations human rights committee to stop the facility from restarting because of risks that the collisions could create dangerous mini–black holes. Independent physicists say such fears are groundless.

    A new clinical trial will explore whether a drug could reverse mental retardation. The federally funded trial by a Massachusetts company will enroll healthy volunteers to assess the safety of a proposed treatment for Fragile X syndrome, the most common cause of mental disability.

    The new budget for the Interior Department includes a request by Congress that the department obtain an independent assessment of ecological risks of oil and gas exploration in the Arctic.

    The top drug policy adviser to the British government was fired after he spoke out against current policy on illegal substances. A number of members of the Advisory Council on the Misuse of Drugs have quit in protest.

    Scientists who study viruses in the natural environment are facing what one called a “nightmare” of disrupted research projects. Filters made by a company named Whatman were crucial to their work, but GE Healthcare decided to discontinue production after purchasing the company last year.

    For more science policy news, visit blogs.sciencemag.org/scienceinsider.

  9. Origins

    On the Origin of Religion

    1. Elizabeth Culotta

    How and when did religion arise? In the 11th essay in Science's series in honor of the Year of Darwin, Elizabeth Culotta explores the human propensity to believe in unseen deities.

    CREDIT: K. SUTLIFF/SCIENCE

    To Charles Darwin, the origin of religious belief was no mystery. “As soon as the important faculties of the imagination, wonder, and curiosity, together with some power of reasoning, had become partially developed, man would naturally crave to understand what was passing around him, and would have vaguely speculated on his own existence,” he wrote in The Descent of Man.

    But our propensity to believe in unseen deities has long puzzled Darwin's scientific descendants. Every human society has had its gods, whether worshipped from Gothic cathedrals or Mayan pyramids. In all cultures, humans pour resources into elaborate religious buildings and rituals, with no obvious boost to survival and reproduction. So how and when did religion arise?

    No consensus yet exists among scientists, but potential answers are emerging from both the archaeological record and studies of the mind itself. Some researchers, exploring religion's effects in society, suggest that it may boost fitness by promoting cooperative behavior. And in the past 15 years, a growing number of researchers have followed Darwin's lead and explored the hypothesis that religion springs naturally from the normal workings of the human mind. This new field, the cognitive science of religion, draws on psychology, anthropology, and neuroscience to understand the mental building blocks of religious thought. “There are functional properties of our cognitive systems that lean toward a belief in supernatural agents, to something like a god,” says experimental psychologist Justin Barrett of the University of Oxford in the United Kingdom.

    Barrett and others see the roots of religion in our sophisticated social cognition. Humans, they say, have a tendency to see signs of “agents”—minds like our own—at work in the world. “We have a tremendous capacity to imbue even inanimate things with beliefs, desires, emotions, and consciousness, … and this is at the core of many religious beliefs,” says Yale University psychologist Paul Bloom.

    Meanwhile, archaeologists seeking signs of ancient religion focus on its inextricable link to another cognitive ability: symbolic behavior. They, too, stress religion's social component. “Religion is a particular form of a larger, social symbolic behavior,” says archaeologist Colin Renfrew of the University of Cambridge in the United Kingdom. So archaeologists explore early religion by excavating sites that reveal the beginnings of symbolic behavior and of complex society.

    Yet these fields are developing chiefly in parallel, and there remains a yawning gap between the material evidence of the archaeological record and the theoretical models of psychologists. Archaeological objects fall short of revealing our ancestors' minds, says Bloom, while on the psychological side, “we need more evidence.”

    Birth of the gods

    When did religious beliefs begin? A likely place to find out is the archaeological record, but inferring “religion” from ancient objects and practices can be a tall order. Many researchers take the use of symbols as a clue to budding spirituality. As far back as 100,000 years ago, people at the South African site of Blombos Cave incised pieces of ochre with geometric designs, creating the first widely recognized signs of symbolic behavior (Science, 30 January, p. 569). Although it's difficult to equate enigmatic lines on a chunk of ochre with a belief system, researchers agree that such use of symbols is a prerequisite for religion, and some argue that religious beliefs must have existed by this time.

    The first deliberate burials are found at roughly the same time, at a site called Qafzeh in Israel, dated to about 95,000 years ago. Researchers have dug up more than 30 individuals, including a 9-year-old child with its legs bent and a deer antler in its arms. And starting about 65,000 years ago or even earlier, Neandertals also sometimes buried their dead. Henry de Lumley of the Institut de Paléontologie Humaine in Paris has referred to these ancient burials as “the birth of metaphysical anguish.”

    But others aren't sure what metaphysical message burial conveys. “There can be lots of reasons to bury things; just look at kids in a sandbox,” says Barrett. Burial by itself, says archaeologist Nicholas Conard of the University of Tübingen in Germany, may best be considered a sign of “protobelief.”

    If they had to name one time and place when the gods were born, Conard and some others might point to 30,000 to 35,000 years ago in Europe. That's when symbolic expression flowered in what's called the Upper Paleolithic explosion (Science, 6 February, p. 709). At this time, Ice Age hunter-gatherers painted strikingly realistic animals—and a few half-animal, half-human figures—on the walls of France's Grotte Chauvet and other caves. They also left small but spectacular figurines in caves in Germany, including a dramatic carved ivory “Venus” reported in May and three “lion-men”—each a carved male body with the head of a lion.

    The “Venus of Hohle Fels” illustrates the difficulties of interpreting such ancient objects: Conard, who discovered it, considers the 6-centimeter figure of a headless woman with huge breasts and carefully carved genitalia to be a religious fertility object, while archaeologist Paul Mellars of the University of Cambridge has called it “paleo-porn.”

    Yet many observers agree that the lionmen, with their combination of human and animal qualities—something seen in many early religions—are strong candidates for a supernatural being or spirit guide. Some go so far as to suggest that the small statues were part of shamanistic rituals, though Conard says we cannot know for sure. “Even if it wasn't shamanism,” he says, “I'd bet the bank it was something I'd consider religious beliefs.”

    The world over.

    All cultures have religious beliefs, though they express them in diverse ways.

    CREDITS: (TOP FROM LEFT TO RIGHT) ISTOCKPHOTO.COM; JUPITERIMAGES; ISTOCKPHOTOS.COM; JUPITERIMAGES; WIKIPEDIA (2); JUPITERIMAGES; WIKIPEDIA (2); WIKIPEDIA; JUPITERIMAGES; WIKIPEDIA (2)

    Twenty thousand years later, humans reached another religious milestone, building what is often considered the world's first temple at the 11,000-year-old site of Göbekli Tepe in Turkey (Science, 18 January 2008, p. 278). There, rows of standing stones up to 6 meters tall march down a high hillside in circles; each massive stone is carved with images of wild animals. “There is the erection of monumental and megalithic architecture for the first time,” says excavator Klaus Schmidt of the German Archaeological Institute in Berlin.

    After this time, more organized sites with apparently religious aspects appear elsewhere. For example, at one of the first settled towns, Çatalhöyük in southern Turkey, excavator Ian Hodder of Stanford University and his crew are finding what they consider copious evidence of spiritual life: feasts with wild bulls, burials of ancestors beneath houses, and sometimes the removal and reinterment of skulls. And yet Hodder notes that separating “religion” from other activities seems arbitrary, as it is not clear that the people of Çatalhöyük themselves separated the religious sphere from the rest of life.

    Renfrew cautions that it might not be possible to know for sure that a culture worshipped gods until we can read their names—that is, until the literate societies of ancient Mesopotamia and Egypt, some 5000 years ago. Those early empires had both secular and religious hierarchies, with priestly elites and sometimes a god-king who ruled both the temporal and spiritual realms. In this view, full-fledged “religion” develops hand in hand with organized social hierarchies. It may be that “you don't necessarily have belief in deities until you have persons of enormously high status, who themselves are close to divine,” like a pharaoh, says Renfrew.

    Signs of the spirit?

    Small, 30,000-year-old figurines from Germany suggest religious belief.

    CREDIT: © ULMER MUSEUM; H.JENSEN, (INSET) © EBERHARD KARLS UNIVERSITY TÜBINGEN

    Born believers?

    While archaeologists trace the outward expressions of religious and symbolic behavior, another group of researchers is trying to trace more subtle building blocks of religious belief, seeking religion's roots in our minds.

    According to the emerging cognitive model of religion, we are so keenly attuned to the designs and desires of other people that we are hypersensitive to signs of “agents”: thinking minds like our own. In what anthropologist Pascal Boyer of Washington University in St. Louis in Missouri has described as a “hypertrophy of social cognition,” we tend to attribute random events or natural phenomena to the agency of another being.

    When it comes to natural phenomena, “we may be intuitive theists,” says cognitive psychologist Deborah Kelemen of Boston University (BU). She has shown in a series of papers that young children prefer “teleological,” or purpose-driven, explanations rather than mechanical ones for natural phenomena.

    For example, in several studies British and American children in first, second, and fourth grades were asked whether rocks are pointy because they are composed of small bits of material or in order to keep animals from sitting on them. The children preferred the teleological explanation. “They give an animistic quality to the rock; it's protecting itself,” Kelemen explains. Further studies have confirmed this tendency. Even Kelemen's own son—who “gets mechanistic explanations of everything”—is not immune: At age 3, after hearing how flowers grow from seeds, his question was, “Who makes the seeds?”

    The point of studying children is that they may better reflect innate rather than cultural biases, says Kelemen. But recent work suggests that it's not just children: Kelemen and Krista Casler of Franklin & Marshall College in Lancaster, Pennsylvania, found the same tendency to ascribe purpose to phenomena like rocks, sand, and lakes in uneducated Romany adults. They also tested BU undergraduates who had taken an average of three college science classes. When the undergrads had to respond under time pressure, they were likely to agree with nonscientific statements such as “The sun radiates heat because warmth nurtures life.”

    “It's hard work to overcome these teleological explanations,” says Kelemen, who adds that the data also suggest an uphill battle for scientific literacy. “When you speed people up, their hard work goes by the wayside.” She's now investigating how professional scientists perform on her tests. Such purpose-driven beliefs are a step on the way to religion, she says. “Things exist for purposes, things are intentionally caused, things are intentionally caused for a purpose by some agent. … You begin to see that a god is a likely thing for a human mind to construct.”

    Other researchers find the work intriguing. “If her data are right, we all from childhood have a bias to see the natural world as purposefully designed,” says Barrett. “It's a small step to suppose that the design has a designer.”

    This predisposition to “creationist” explanations has resonance with another tendency in the human mind, says Barrett—something he calls the “hypersensitive agency detection device”: looking for a thinking “being” even in nonliving things. In classic experiments in the 1940s, psychologists found that people watching animations of circles, triangles, and squares darting about could identify various shapes as characters and infer a narrative. Anthropologist Stewart Guthrie noted in 1993 that this tendency could help explain religion, because it implies we attribute “agency” to all kinds of inanimate objects and ambiguous signals. As Barrett describes it: “When I hear a bump in the night, I think ‘Who's there?’ not ‘What's there?’ … Given ambiguous stimuli, we often posit an agency at play.”

    Raising the temple.

    The standing stones at Göbekli Tepe are considered by many to be the oldest humanmade holy place.

    CREDIT: BERTHOLD STEINHILBER/REDUX

    Guthrie suggested that natural selection primed this system for false positives, because if the bump in the night is really a burglar—or a lion—you could be in danger, while if it's just the wind, no harm done.

    Of course, this is still a long way from believing in gods or spirits. But a hair-trigger agency detector could work with another sophisticated element of the human mind to make us prone to believe in gods, cognitive researchers say. They refer to what's called theory of mind, or the understanding that another being has a mind with intentions, desires, and beliefs of its own. Studies have shown that this ability develops over time in children and is usually present by age 5; functional magnetic resonance imaging (fMRI) studies have localized the parts of the brain involved.

    Who made it?

    Studies suggest that children tend toward creationist explanations of natural phenomena.

    CREDIT: JUPITERIMAGES

    If you suspect that an agent was responsible for some mysterious event, it's a short step to thinking that the agent has a mind like your own. “Higher order theory of mind enables you to represent mental states of beings not immediately or visibly present, and who could have a very different perspective than your own,” says Barrett. “That's what you need to have a rich representation of what it might be like to be a god.” (It's also what is needed to have a functional religion, because people need to know that others share their beliefs.) As Darwin put it, humans developing religion “would naturally attribute to spirits the same passions, the same love of vengeance, or simplest form of justice, and the same affections which they themselves feel.”

    Some fMRI studies lend support to this idea. In the 24 March issue of the Proceedings of the National Academy of Sciences, a team led by Jordan Grafman of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, asked 40 people to evaluate statements about God's emotions and relationships to humans, such as, “God is removed from the world” and “God is forgiving,” while they were in an fMRI scanner. The researchers found that the areas that lit up (indicating oxygen uptake and so presumably brain activity), such as the inferior frontal gyrus on both sides of the brain, are also involved in theory of mind. This and other results argue against any special “god region” of the brain as some have suggested, says Grafman. Rather, he says, “religious belief co-opts widely distributed brain sectors, including many concerned with so-called theory of mind.”

    Other researchers are extending this cognitive model, finding additional thought processes that they say make religious belief natural. For example, Bloom and Jesse Bering of Queens University Belfast argue that children are predisposed to think that the mind persists even after the death of the body—something that approaches the idea of an afterlife. Bering showed children ages 4 through 12 years old a puppet show in which a crocodile ate a mouse. Then he asked the children questions about the mouse. Did it feel hunger? Was it still mad at its brother? The children agreed that the mouse's body no longer functioned; it didn't need to eat, for example. But they thought it would still feel hunger; its psychological states persisted. Preschoolers showed this tendency more than older children.

    We can acknowledge the death of the body, says Bering, but we believe that the mind continues: “We have this unshakeable sense that our minds are immortal.” Bloom notes that this kind of belief “is universal. You won't find a community anywhere where most people don't believe that they are separate from their bodies.”

    Mind or soul?

    Such hypotheses seem to make intuitive sense. But critics such as Paul Harris of Harvard University say that children learn about the afterlife from others. Working in Spain and Madagascar, Harris and colleagues did studies somewhat similar to Bering's, asking children about the physical and psychological states of a person who had died. Older children and adults were more likely than younger children to think that psychological states continued after death, suggesting that ideas of the afterlife are learned. What's more, people in many cultures distinguish between the mind, which learns and changes over time, and something like an unchangeable soul, says Harris. “To say that there is a continuance of mind after death misrepresents these people's beliefs,” he says. “I think people are disposed not to dualism but to ‘triadism’” of mind, body, and soul.

    Even those who embrace the cognitive model concede that more studies are needed to distinguish what is learned from what is innate. As for hypersensitive agency detection, “it's a compelling idea, but I haven't seen lots of empirical evidence that you can get from there to religious beliefs,” says social psychologist Ara Norenzayan of the University of British Columbia, Vancouver, in Canada.

    Indeed, even if more data are forthcoming, such models are a long way from explaining the complex systems of gods and rituals that make up religion. Cognitive researchers face what has come to be called the “Mickey Mouse” problem: The Disney character Mickey Mouse has supernatural powers, but no one worships or would fight—or kill—for him. Our social brains may help explain why children the world over are attracted to talking teacups, but religion is much more than that. “Deriving belief from the architecture of the mind is necessary but not sufficient,” says Norenzayan.

    Social circuits.

    When subjects in an fMRI scanner thought about God's relationship with humans, a part of the brain involved in understanding the thoughts of others lit up (top right).

    CREDIT: (INSET) D. KAPOGIANNIS ET AL., PNAS, MARCH 2009; D. AMODIO & C. FRITH, NATURE, 7, APRIL 2006

    He favors an additional class of explanations for why religion is so prominent in every culture: It promotes cooperative behavior among strangers and so creates stable groups (Science, 3 October 2008, p. 58). Other researchers hypothesize that religion is actually adaptive: By encouraging helpful behavior, religious groups boost the biological survival and reproduction of their members. Adhering to strict behavioral rules may signal that a religion's members are strongly committed to the group and so will not seek a free ride, a perennial problem in cooperative groups (Science, 4 September, p. 1196).

    Norenzayan and others also note that helpful behavior is more common when people think that they are being watched, so a supernatural god concerned with morality could encourage helpful behaviors, especially in large groups where anonymity is possible. Some researchers suggest that cognitive tendencies led to religion, which then took hold and spread because it raised fitness.

    But others, such as Boyer, counter that this adaptationist explanation is itself light on data. “It is often said that religion encourages or prescribes solidarity within the group, but we need evidence that people actually follow [their religion's] recommendations,” says Boyer. “The case is still open.”

    Meanwhile, disciplinary gaps persist among archaeology, psychology, and neuroscience. Cognitive types insist that ancient objects can answer only a small subset of questions, while some archaeologists dismiss the cognitive model as speculation. Yet there have been some stirrings of interdisciplinary activity. Archaeologist Steven Mithen of the University of Reading in the United Kingdom has suggested that the half-human, half-animal paintings and carvings of the Paleolithic demonstrate that early Homo sapiens were applying theory of mind to other animals 30,000 years ago. And anthropologists focusing on the development of religion are finding signs of key changes in ritual at archaeological sites like Çatalhöyük. All agree that the field is experiencing a surge of interest, with perhaps the best yet to come. “In the next 10 to 15 years there's likely to be quite a transformation, with a lot more evidence, to give us a compelling story about how religion arose,” says Norenzayan.

  10. 20 Years After the Wall

    Aufbau Ost: Max Planck's East German Experiment

    1. Gretchen Vogel

    The Max Planck Society's expansion into the former East Germany seeded top science into the region, but challenges remain in making sure the successes take root.

    In September and October 1989, thousands of East Germans gathered each Monday evening in the city of Leipzig, chanting, “We are the people!” in peaceful protests against their government. The so-called Monday demonstrations were central to the popular movement that toppled the East German dictatorship, which 20 years ago this week opened its borders and checkpoints in the divided city of Berlin, allowing its citizens to travel west. Today, Leipzig is home to cutting-edge research into what it means to be human. Scientists at the city's Max Planck Institute for Evolutionary Anthropology and its Max Planck Institute for Human Cognitive and Brain Sciences are at the forefront of probing how the human mind evolved and works.

    When those courageous protesters filled the city streets, Leipzig was a scientific backwater. So how did it achieve its current reputation for research excellence? It's one of the fruits of an ambitious effort by the then–West German Max Planck Society to seed topflight research institutes throughout formerly communist East Germany. Known as Aufbau Ost—the phrase means “building up the East”—the project resulted in 20 new outposts of the society within 7 years, several in fields that had been dormant in Germany for a generation. “It was a chance to do something completely new and to be courageous” in picking research areas, says Peter Gruss, the current Max Planck Society president.

    Breakthrough.

    The opening of the Berlin Wall meant dramatic changes for East German research.

    CREDIT: TOM STODDART/GETTY IMAGES

    A decade after the last “Eastern” Max Planck institute was founded, the region draws scientists from around the world to study topics as diverse as human evolution, gravitational physics, and the way cells become organs. Observers agree that the society's expansion has been a success—in that it attracted top-class research to eastern Germany. Within the Max Planck Society, there are no noticeable differences between east and west, says Jonathan Gershenzon, director at the Max Planck Institute for Chemical Ecology in Jena. And he has no trouble recruiting talent, he says: “Students are moving from west to east without any concern. People come—there's no hesitation. In that sense, the wall really has been torn down.”

    But the success of Max Planck's Aufbau Ost wasn't quick and easy, and it isn't complete. Some of the new institutes struggled for years, particularly those burdened with researchers inherited from the East German system or with founding directors who didn't click. And the overall influence of these research oases hasn't yet spread as far as some had hoped. The region's universities, which after reunification underwent a more gradual reformation than the East German Academies, still lag behind their western counterparts. And eastern Germany's industrial base, which largely started from scratch 2 decades ago, still struggles. “Science is really successful when researchers can see their research reflected in the regional economy,” says Hans-Peter Hiepe, who administers the German science ministry's programs for the former East.

    Growing pains

    In October 1990, less than a year after the Berlin Wall opened, East and West Germany officially reunited. That marked the start of a swift and fundamental transformation of East Germany's research landscape. Under the unification agreement, the West German Council of Science and Humanities (an official advisory body that evaluates the country's research and higher education systems) undertook a rigorous evaluation of the East German Academy of Sciences, which administered dozens of institutes across the sciences and humanities. Within a year, eastern institutes were dissolved, renamed, or often “filleted” and divided between different West German funding organizations. There was also a short-term effort to support top East German scientists (see sidebar, p. 791).

    The Max Planck Society, however, was able to take a longer view. Formed in Germany in 1948, it was West Germany's premier science funding agency after World War II. By 1989, it was running 60 institutes, each led by a handful of directors who receive lifetime appointments and steady funding. The society receives a government-allocated budget but retains the freedom to set its own research agenda, using working groups of current directors to come up with ideas for new institutes.

    Human power.

    Hundreds of thousands gathered in Leipzig's famous “Monday demonstrations,” which helped topple the East German regime. Today the city is a major center of research.

    CREDIT: CHRIS NIEDENTHAL/TIME & LIFE PICTURES/GETTY IMAGES

    After the 1989 revolution, initial proposals suggested that the society should thin out its ranks in West Germany to help populate the East, says Andreas Trepte, who helped coordinate Max Planck's Aufbau Ost programs and today works with the society's outreach programs. (A resident of Leipzig in 1989, Trepte participated in the Monday demonstrations.) But the society's president at the time, Hans Zacher, convinced politicians that the current level of research funding in West Germany should be a benchmark—and that the society should expand in proportion to the reunited country's new population.

    Keeping with Max Planck tradition, existing directors proposed and debated the focus or theme of each new institute. Working groups looked for areas in which German research was weak, such as anthropology and earth sciences, “or at the absolute interface bridging disciplines,” says Gruss, who at the time was a director at the Max Planck Institute for Biophysical Chemistry in Göttingen. Within 7 years, the East had 18 Max Planck institutes, one subinstitute, and one research unit. The society did receive 5% budget increases for nearly a decade to fund the expansion, but it still meant significant belt-tightening in the West, where institutes faced flat budgets for several years and four were ultimately closed.

    The first two eastern society outposts—the Institute of Microstructure Physics in Halle and the Institute of Colloids and Interfaces in Berlin—were started in 1991. Both took over researchers and topics from institutes in the East German Academy of Sciences. The Council of Science and Humanities in its evaluation had found that the East German researchers there had enough potential to join the Max Planck ranks.

    Taking them aboard wasn't painless, says Helmuth Möhwald, one of the original directors at the Colloids and Interfaces center. Although the academy scientists were doing fine work, they often didn't fit into the research plans of the new directors, he says. In his department of 130, “there were at least 30 or 40 who didn't belong but had to be kept working somehow; … there were too many to simply let them all go,” Möhwald says. To make matters worse, the institute was housed in antiquated labs and was split between two locations in East Berlin. The early years “were the worst professional time of my life,” Möhwald says, and he often regretted taking the job.

    Gradually, Möhwald recalls, he and his imported colleagues found “soft solutions” as they trimmed their staff. “Not more than two out of 100 ended up jobless,” he says. The original academy scientists who stayed, he says, were well-trained and highly motivated, and the early hardships started to pay off. In 1999, the institute moved to a state-of-the-art building in Golm, a village just outside Potsdam. When the Council of Science and Humanities evaluated chemistry departments at universities and institutes across Germany in 2007, the departments in Golm were among a handful that received top marks. And earlier this year, Möhwald's fellow director, Markus Antonietti, received a prestigious Advanced Grant from the European Research Council—one of just two dozen German researchers to do so.

    Beyond Germany

    Science Online Logo The fall of the Berlin Wall is the most potent symbol of the revolutionary events that took place in 1989 in the former Eastern bloc, but Europe's transformation went far beyond Germany's borders. That year's downfall of the dictator Nicolae Ceauşescu, for example, brought tremendous change to Romania—and to its research landscape (Science, 21 November 2008, p. 1184). In addition to the stories here on Germany, Science Careers takes a look online at current science opportunities in Eastern Europe, profiling young researchers and examining programs that promote cooperation between the economically challenged region and wealthier counterparts in Western Europe and throughout the world.

    New starts

    The directors who started Max Planck Society institutes from scratch had an easier time. “It is one of the most fantastic things that has happened in my life,” says anthropologist Jean-Jacques Hublin, a director at the Max Planck Institute for Evolutionary Anthropology, which began work in 1997. “Building a department up from scratch, the way you want, with the techniques and people you've only dreamed of—it is an extremely rare chance in science.” Another director at the institute, linguist Bernard Comrie, agrees. “This was a once-in-a-lifetime offer,” he says.

    That particular Leipzig institute was an unusual chance for the Max Planck Society as well. For more than half a century, anthropology had largely been a taboo subject in Germany. Until the 1930s, Germany produced some of the world's most influential anthropologists, says Hublin, but “the Nazi regime and the World War almost completely killed the field.” It's risen from the ashes in Leipzig. After just a few years, the institute, which now employs nearly 500 people, “has been called the mecca of evolutionary anthropology by some of our colleagues,” Hublin says.

    Hublin's new scientific home in Leipzig (he was recruited from France) was also an experiment in interdisciplinary research. The five directors—Hublin, Comrie, primatologist Christophe Boesch, psychologist Michael Tomasello, and molecular geneticist Svante Pääbo—come from very different fields, but together they have managed to build a coherent institute. The resulting mix of ideas has led to unexpected projects, Pääbo says, such as looking for the genetic basis of domestication in dogs and rats. “If I had been at an institute of molecular genetics, these are not things I would have been exposed to,” he says.

    None of the directors at the Evolutionary Anthropology institute is a German citizen. That's not unusual among the Aufbau Ost institutes; nearly two-thirds of the society's directors in the East come from outside Germany. In some cases, such as evolutionary anthropology, Germany had few experts to choose from.

    Often, however, foreigners were less intimidated than West German scientists by the so-called Wild East, with its gray, crumbling cities and its society undergoing a wrenching transition from a repressive socialist regime to a democracy with a market-driven economy. “This was the first time in history that a Max Planck offer wasn't as attractive for Germans” as for outsiders, says American ecologist Ian Baldwin, director at the Max Planck Institute for Chemical Ecology in Jena.

    Before and after.

    The Max Planck Institute for Infection Biology (left) stands just meters from the former path of the wall (right) in Berlin. The Max Planck Society spent €530 million on building new institutes in the East.

    CREDITS: (SOURCE) MAX PLANCK; (PHOTOS, LEFT TO RIGHT) JOCHEN JANSEN; M.JOEDICKE/FLICKR

    When Baldwin and another American, biochemist Gershenzon, came to Germany for their recruiting visit, their hosts allowed them “barely 24 hours” in Jena, Gershenzon says. “What I only later realized was that the people who showed us around—West German scientists—would not have taken the job we were being offered.” Once back in Tübingen, in Germany's prosperous southwest, their hosts relaxed visibly. “Over a beer one evening they said, ‘You know, in 30 years Jena could look a bit like Tübingen,’” Gershenzon laughs. “But that wasn't what we were looking for.” To him, moving to Jena was exotic and exciting instead of daunting.

    That excitement carried over into the scientists' work. “In the first weeks I was here, I almost couldn't sleep,” says Hublin. “I would often go in at 4 a.m. There was so much excitement I couldn't stay still.”

    The chemistry didn't always work as well as it did in Leipzig. At the Institute for Biogeochemistry in Jena, also founded in 1997, two of the three founding directors had left by 2004, along with three other professor-level scientists. Personal strains proved to be too much, especially for two-scientist couples for whom the only local career option was to work in the same institute, with one spouse supervising the other. And disagreements between directors didn't help. “There was increasing friction in the whole organization of the institute,” says ecologist Ernst-Detlef Schulze, the one founding director who remained. He says the former East German location isn't to blame, however. “The whole thing would have crashed in the West, too,” he says. Originally, there had been plans to have as many as five directors, he says, “but that did not materialize. We simply had too many internal problems. … We were set back, kept busy refilling positions.”

    The institute, most agree, is now on firmer footing. “It's an example of an institute that needed two starts,” says Baldwin, who observed the difficulties up close while the two Jena institutes shared a building as new labs were under construction. “A lot of times it works, but when that special chemistry doesn't occur, it can go sour.” The growing pains were something new for the Max Planck Society, Baldwin says. “It was the first time in the history of the Max Planck that people wanted to leave the society,” he says. Given that the organization hired nearly 60 directors in less than a decade, “if something like that hadn't happened, you would almost have to say that the Max Planck didn't take enough risks,” says Wilhelm Krull, secretary general of the Volkswagen Foundation in Hannover, who worked at the German Science Council from 1987 until 1993 and at Max Planck headquarters from 1993 until 1995.

    Heidelberg East

    On balance, Krull says, the brand-new institutes in the former East Germany have panned out well: “You can see that in some areas, starting from scratch and setting up something with an international reputation really helped to put these spots on the map.”

    One of those bright spots, Krull says, is Dresden. The city, once dubbed “the valley of the clueless” because it was cut off from West German television and radio signals, is now the leading research center in the former East. It is home to three new Max Plancks: the Institute for Chemical Physics of Solids, the Institute for the Physics of Complex Systems, and the Institute of Molecular Cell Biology and Genetics. The latter lured four researchers from Heidelberg, home to one of Germany's best universities and the European Molecular Biology Laboratory, to start over in Dresden. The four directors from Heidelberg—Kai Simons, Wieland Huttner, Marino Zerial, and Anthony Hyman—along with a fifth director, Jonathan Howard of the University of Washington, Seattle, decided to forgo having “departments” of scientists who answered to them and instead gave younger colleagues the chance to help guide the institute. The model, a significant departure from the traditional Max Planck setup, has worked well, Simons says.

    “The real question mark in our equation when we moved,” Simons notes, “was could we recruit Ph.D. students and postdocs?” Less than a decade later, the answer seems to be yes. This year, the institute was named the top place to work as a biology postdoc in an international survey commissioned by The Scientist magazine. “Within a few years, they've managed to make Dresden almost like Heidelberg,” says Krull.

    Dresden may also be the clearest success story in terms of Aufbau Ost institutes having a spinoff effect on the region. The Max Planck institutes there are now surrounded by several related research institutes, and more than two dozen technology start-ups have sprung up in the region. The society's institutes have served as a “crystallization core,” says Gruss. “It's a wonderful example of how science can drive business.” In the country's recent Excellence Initiative, which offered universities a chance to get extra funding in a bid to boost a few to world-class status (Science, 20 October 2006, p. 400), the Dresden University of Technology received funding for two of its projects, both cooperative efforts with the neighboring Max Planck institutes. It was the only university in the former East outside of Berlin to do as well.

    Cooperation counts

    In western Germany, relations between Max Planck and universities have often been strained, frequently characterized by rivalry. That hasn't been the case with the new institutes in Dresden and elsewhere. “It is something that is very striking in Leipzig compared to Munich,” says Pääbo, who was a professor at Ludwig Maximilian University of Munich before moving to Leipzig. “Here we are much more cooperative and open with the university.”

    The good relations are partly the result of the society's overall effort to repair historical rifts. In 1999, it began a new program of International Max Planck Research Schools throughout Germany. Students in the interdisciplinary graduate programs study at the cooperating university and can do research at a Max Planck institute. “It makes it a whole lot easier to integrate the institutes with the university and get away from the castle concept that had led to the jealousies and animosities” common in the west, Baldwin says.

    However, the relatively weak showing of eastern universities overall in Germany's Excellence Initiative worries many observers. Although the new Max Planck institutes themselves are producing good science, the overall research landscape around them is not yet strong enough to stand on its own, says Hiepe. “It is as though you've just moved into a beautiful new house, the envy of all the neighbors. But soon you discover that the foundation is made of matchsticks,” he says.

    “There is still a lot to be done to make eastern Germany more competitive,” Krull agrees. Most important, he says, the universities “need extra money, resources, and infrastructure.” And time is running short, Hiepe says. The eastern states within Germany have received extra infrastructure funding from the European Union for 2 decades, but that runs out in 2013. And the German “solidarity pact” that has transferred billions of tax dollars to development projects in the East will also phase out by 2019. The research institutes and the universities of the region have to continue to pull together, Hiepe says. The institutes “have to realize that their future is dependent on the university and local companies also doing well,” he says.

    Schulze, for one, is in the East for the long term. He retired in September, but he and his wife will stay in Jena, he says. His three children, who grew up in West Germany, all migrated east with their parents. “My son decided to study engineering in Dresden, my elder daughter has a job in Potsdam, and the other has a job in Jena,” he says. “We are very happy to be here. We won't move back to the west.”

  11. 20 Years After the Wall

    Why So Few East German Directors?

    1. Gretchen Vogel

    The reunification of Germany was a mixed blessing for East German scientists. For many, especially the younger ones, it was a great opportunity (see p. 792). But others were set adrift when entire preexisting eastern institutes were closed or cut to a fraction of their original size.

    When the Max Planck Society planted institutes across the former East Germany, it recruited scientists from around the world for its ambitious Aufbau Ost project (see main text). But only two out of more than 60 directors in the newly founded institutes were recruited from the East itself. Today, the society has 267 active directors; only five grew up on the eastern side of the divided Germany. And only one started a career before 1989.

    Those statistics are a sign of the mixed blessings that reunification brought for East German scientists. For many, especially the younger ones, it was a great opportunity (see p. 792). But others were set adrift when entire preexisting eastern institutes were closed or cut to a fraction of their original size. Universities, dominated by the Communist Party, were reorganized, and researchers had to compete with West Germans.

    As Max Planck undertook its expansion, it was clear that even the best East German researchers simply weren't in a position to head the new institutes, says Andreas Trepte of the Max Planck Society. “The development of a director needs time, and it was unusual to find someone who was in a leading position in research who had not been involved in politics” and associated in some way with the Communist Party, he says. Those who had stayed out of the party had faced severe career hurdles, Trepte notes, “so no one had the profile” as a leader that was needed to be an institute director.

    To support top East German scientists and give the region's higher education an early boost, the Max Planck Society started a short-term program in November 1990 that gave 28 selected investigators 5 years of funding and administrative support to work at a host university. The university had to agree to hire the researchers as regular professors together with their research teams by the end of the 5-year term.

    Extra boost.

    Chemist Joachim Sauer received funding as leader of a Max Planck Research Group after German reunification.

    CREDIT: JOHANNA LEGUERRE/AFP PHOTO/NEWSCOM

    “It was the best thing that could happen to a scientist from the East at that time,” says chemist Joachim Sauer, who led one of the Max Planck research groups and today is a professor at Humboldt University of Berlin. One of the 28 research groups, headed by biochemist Gunter Fischer, was eventually made into the Max Planck Research Unit for Enzymology of Protein Folding, which today employs 60 scientists in Halle. Today, Fischer is the lone active Max Planck director who had been a professor in East Germany. Four other directors grew up in the East, but they were all graduate students or postdocs when the wall fell.

    “There is simply a generation who had already spent too much of their career in the GDR [German Democratic Republic],” says Trepte. Sauer agrees. “I don't think anyone was overlooked” in the search for new directors, he says. Trepte predicts that the proportion of “Eastern” directors will steadily increase in the coming years. “But really,” he adds, “no one is paying attention anymore” to whether someone comes from east or west of the former wall. That, perhaps, is one of the best signs that Max Planck's Aufbau Ost has been a success.

  12. 20 Years After the Wall: Profile: Hübner Family

    Big Dreams Come True

    1. Andrew Curry*

    An East German family of scientists reflects on life before and after 1989. The Hübners have become a dynamic demonstration of how the lives of scientists in the former East Germany have changed over the past 2 decades.

    Meet the Hübners.

    Georg, Gerhard, Christian, Gertraude, Dorothee (l-r) in East Germany.

    CREDIT: COURTESY OF DOROTHEE KERN

    On 9 November 1989, 23-year-old Dorothee Hübner gathered with her family around their television in the East German city of Halle. As a brand-new biochemistry doctoral student, she was following in the footsteps of her father, Gerhard, and mother, Gertraude, both trained as biochemists at Martin Luther University of Halle-Wittenberg.

    Watching crowds of East Germans flood across the Berlin Wall that night, the daughter realized that her life was going to be very different from that of her parents, who had spent decades struggling to do research in East Germany without compromising their personal ideals with allegiance to the ruling Communist Party. “It wasn't until the wall came down that we thought, ‘Are we allowed to leave and finally be free?’” she says.

    Indeed, the young biochemist soon left Halle, marrying (and becoming Dorothee Kern), settling in the United States, and thriving outside of Germany's rigidly hierarchical scientific establishment, which persisted even after the wall fell. She successfully juggled her career and family life. Dorothee and her husband, now a scientist at pharmaceutical giant AstraZeneca, had two daughters, yet by 1998 she had also become a professor at Brandeis University in Waltham, Massachusetts, and subsequently landed a prestigious Howard Hughes Medical Institute position.

    Her parents pursued their newfound freedom at home—as did, eventually, her younger brother Christian, who, after taking positions outside the country, became a physicist in Germany. Taken together, that family watching television in 1989 has become a dynamic demonstration of how the lives of scientists in the former East Germany have changed over the past 2 decades.

    Saying no to the Stasi

    Before 1989, science in the German Democratic Republic, like almost everything else, was political. Everything from university admissions to teaching positions depended on allegiance to the Communist Party. Ideology also affected the substance of academic work, especially in disciplines such as history, linguistics, and political science. “There was a big difference between the natural sciences and the humanities because the humanities and social sciences were part of the legitimacy and ideology of the Communist worldview,” says Dieter Hoffmann of the Max Planck Institute for the History of Science in Berlin.

    Joining the party was a prerequisite for advancement; researchers felt pressure to collaborate with the Stasi, the secret police, as well. “In science, many persons were asked from the Stasi to work for them,” says enzymologist Gunter Fischer, who was a colleague of Gerhard Hübner's at the time and is now at the Martin Luther University Halle-Wittenberg.

    It was a difficult offer to refuse. In exchange for signing a loyalty oath and an agreement to report back to the Stasi on friends and colleagues, you could attend international conferences and have your career fast-tracked, Fischer says. “If you said no, you'd have no higher-ranking position or travel, and you might lose your job,” he notes. The pressure went beyond career and travel to petty indignities. Party members were given the best lab times. Non–party members could only use equipment between 1 a.m. and 3 a.m., Gerhard recalls.

    Committed Christians, the Hübners refused to give in; they surrounded themselves with like-minded friends and colleagues. “My parents were never hiding what they were thinking about the whole system,” Dorothee remembers. “We knew scientists who were honest and didn't join the party and sell their soul just to have advantages.”

    After the wall fell, records emerged showing that the Stasi was planning to force Gerhard Hübner and Fischer out of their university jobs; disgruntled party members claimed the two biochemists were “treating the lab equipment as their private property.” Asked about the incident today, Gerhard shrugs. “The ‘comrades’ weren't the best students,” he says. “We didn't want them to break it. It was really hard to get spare parts.”

    Although their supervisor was prominent enough to protect the people in his lab regardless of their politics, Gerhard's official position was scientific assistant (oberassistent). His wife wasn't able to get a university position at all. Instead, their adviser found her a job in industry, coming up with ersatz chemical solutions to East Germany's food production problems: artificially aging schnapps and making fake caviar. Professorships and teaching positions were restricted to members of the party. Nonconformity had other implications. “You couldn't speak your mind,” Gerhard says. “There was always the fear that you could say something that could have harmed your spouse or kids by accident.”

    For the three Hübner children, their parent's politics meant a struggle to get into university. The oldest son, Georg, now a chief doctor at a hospital in Germany, secured a university slot. Local officials made it clear that the prospects for Dorothee and her brother Christian were much dimmer. “There was always this goal to bring children from the working class into the university, not children with academic parents,” Christian says. “Of course, if academic parents belonged to the party, somehow they still counted as part of the working class.”

    Sports ultimately gave Dorothee her ticket to higher education. After a special sports school recruited their athletic daughter as a fifth grader, the parents made a calculated move to keep her in regular school, steering her away from swimming and into basketball. Swimming and other sports where East Germany many had a chance at Olympic success were under high pressure to produce results. It was common for coaches to press their athletes to dope. In contrast, sports such as basketball were considered hopeless as far as Olympic medals went.

    Dorothee's basketball prowess earned her a spot in high school and later at university. She ended up playing point guard on the East German national team, a position that suited her personality. “I like to be in charge of the game,” she says. By 1989, she was the national team captain and a graduate student at Halle.

    Dorothee faced a future similar to her parent's lives: scientific isolation behind the Iron Curtain, experimenting for the love of it. For scientists, East Germany was one of the most restrictive countries in the Soviet bloc, notes Hoffmann. Publishing outside the country required special permission.

    Like most of the Communist bloc, East Germany was in a perpetual state of financial crisis. Sophisticated lab equipment—such as the nuclear magnetic resonance (NMR) scanners Gerhard and later his daughter needed for their work on protein folding and enzymes—was hard to come by. Biophysical chemist Sture Forsén, who ran a lab in Lund, Sweden, in the 1980s and '90s and is now the director of the Pufendorf Institute at the University of Lund, remembers encountering researchers from behind the Iron Curtain. “There were many good scientists,” Forsén says. “The problem was they didn't have proper equipment available and couldn't travel. They were like a kid standing outside a candy store with big eyes, looking in.”

    CREDITS: COURTESY OF DOROTHEE KERN

    Dorothee and her father both note that the situation forced the best East German scientists to be more creative and improvise. The scarcity of resources also influenced what people learned. “The theoretical education, honestly, was better than in West Germany. It was stricter, the pressure was higher, and there were fewer students,” Dorothee says. “Our basic knowledge was on a very high level.”

    With no pressure to compete for grants or to get into the most prestigious journals, scientists pursued ideas and experiments that might not have been given funding in the West. Dorothee is convinced that the experiments that she is best known for today—including unusual approaches to measuring the way protein structures shift and change, cutting across the fields of chemistry, physics, and biology—are rooted in this improvisational spirit.

    Still, Dorothee readily acknowledges that the end of communism changed everything. “It couldn't have come at a better time,” she says. “I couldn't go any further without having a better NMR machine.” When the wall fell just a month into her Ph.D., she set out to look for labs that would let her follow her interest in protein folding; she ended up approaching Forsén with big eyes.

    In 1990, Dorothee began commuting by train and ferry from Halle to Lund to conduct experiments in Forsén's lab there. She would spend 4 years juggling her Ph.D. research in two countries with competitive basketball on the unified German national team and Halle's local team. Her energy made an impression on colleagues. “She was bouncing around the lab all the time,” Forsén remembers. “She's not very tall, but she was made captain of the national team—that tells you something of her qualities.”

    Empowered by her new freedom, Dorothee next moved on to a postdoc in the United States before landing at Brandeis. Already a young mother, she found the American academic world more accepting of women scientists. “The attitude in Germany was either have a family or do science,” she says. “I came over here and it was the opposite. It's really a blessing.”

    After the fall

    Many weren't as nimble at navigating the transition. The fall of the wall turned East German science on its head. The Stasi archives were opened in 1991, revealing that some of the country's top scientists had been collaborators and forcing them out of universities. In the social sciences, entire institutes were simply closed, their scholarship too tainted by ideology to salvage. And after decades of isolation, an entire generation of scientists suddenly had to compete for jobs with West Germans and others. Gerhard found himself the lone East German in the running for a position as the chair of his department, up against more than 30 West Germans—he won.

    The country's reunification did bring the Hübner family an unexpected benefit. Dorothee met her future husband at the first combined meeting of the East and West German biochemical societies. Her first paper in Science, a 1997 report on how vitamin B-1 is activated in enzymes, was a family affair, with her husband and father as co-authors.

    Dorothee's collaborations now continue with Christian, who back in 1989 had just entered university at Halle, where he studied physics. He remembers the years after the end of communism as chaotic and distracting. “For the first few years of my studies, the old order had gone and there was no new order,” he says. Christian worked for a local parliamentary candidate's campaign and might have left science if his boss had won a seat in 1994. Instead, he went on to study in the United States and Switzerland, returning to Halle as a professor in 2003. When the University of Lbeck made an offer Halle couldn't match—head of its physics institute—he accepted. Christian recently co-authored a paper in Nature with his sister, helping her team dissect the dynamics of a single molecule in real time.

    Like many of their East German contemporaries in the 1980s, the Hübner family never expected the system to change. Yet deep inside, Dorothee says she had always held out hope. “It was my dream since I was a little kid to go to America, study science, and play basketball,” she says. “It's always good to have big dreams.”

    • * Andrew Curry is a freelance writer based in Berlin.

  13. DNA Sequencing

    No Genome Left Behind

    1. Elizabeth Pennisi

    A project to sequence 10,000 vertebrates has just been launched, but sequencing technologies are not yet up to the task.

    Times have changed. A decade ago, it took several rooms full of sequencing machines and millions of dollars to decipher the genome of a small nematode. This month, two sequencing machines and $500,000 yielded a draft of the far more complex DNA of the cod. Now, a group of genome and museum experts are calling for the unraveling of 10,000 vertebrate genomes, about one per genus across the backboned animal world. They have already set in motion a global effort to gather the DNA needed for such an undertaking. “This is the most comprehensive experiment that anyone has ever proposed to analyze the evolution of genomes,” says Oliver Ryder, a conservation biologist at the San Diego Zoo in California.

    The Genome 10K plan, formally announced this week, is short on details: where funding will come from; what sequencing strategy to use; and how to process and make use of the data generated. But supporters are gung ho. “It's a grand plan that will happen,” predicts Joel Cracraft, an ornithologist at the American Museum of Natural History in New York City.

    New sequencing technologies aided the rapid completion of the cod genome project, one of about a half-dozen efforts using advanced, low-cost methods to analyze large vertebrate genomes, originally considered too complex to be unraveled with the newer technologies. And better tools are coming online. Besides, says Byrappa Venkatesh of the Institute of Molecular and Cell Biology in Singapore, there's a precedent for being impetuous: “After all, when the Human Genome Project was launched, there was neither an appropriate technology for sequencing a complex genome nor a suitable algorithm for assembling and annotating” the results.

    Molecular menagerie.

    These animals and thousands of other vertebrates may one day have their genomes sequenced.

    CREDITS (LEFT TO RIGHT): SAN DIEGO ZOO/WWW.SANDIEGOZOO.ORG; AMNH; ANDREW J. CRAWFORD; SAN DIEGO ZOO/WWW.SANDIEGOZOO.ORG

    Beyond the human genome

    Ever since they finished the human genome sequence, researchers have been champing at the bit to sequence other genomes to compare with human DNA. Such comparisons help identify conserved regions that likely serve key roles in survival and also regions that differ between species and likely represent adaptations to a particular way of life.

    With that in mind, the National Human Genome Research Institute (NHGRI) 5 years ago began to assemble a list of 32 mammals and 24 other vertebrates that would make good candidates for analysis. David Haussler of the University of California, Santa Cruz, and Stephen O'Brien of the National Cancer Institute in Frederick, Maryland, were part of the selection committee. “One of the most difficult things was to get specimens that had good DNA,” O'Brien recalls. Anticipating that genome sequencing will get much cheaper, Haussler, O'Brien, and Ryder decided to prepare for a full-out assault on vertebrates.

    The three organized a meeting in April at which 50 participants from the United States, Canada, South and Central America, Europe, and Asia came up with a list of 10,000 candidates, one-sixth of the known vertebrates. After an evening of hashing out reservations and concerns, they divided into animal-specific groups to see what suitable DNA existed, and where. To their surprise, they concluded that freezers around the world held DNA from more than 16,000 species.

    As described online 5 November in the Journal of Heredity, the Genome 10K project has compiled a list of tissue samples from more than 43 institutions. For 600 species, cell lines already exist; the plan calls for establishing cell lines for 2000 more species. In addition, the researchers want to sequence several individuals for at least one species per order.

    Advocates say the project will reveal new information about the human genome and basic biology. With dense sampling, “the insights into genome evolution and speciation from an evolutionary perspective would be extremely powerful,” says William Murphy of Texas A&M University in College Station. Cracraft, for example, is curious about grebes and flamingos, which look nothing alike. “The question is how to account for that disparity in biology and form,” says Cracraft. “Whole genomes are really going to spur things on.”

    Others believe the endeavor is essential to aid conservation efforts. “Wait another 20 years and it will be too late for several species,” says Olivier Hanotte, a conservation biologist at the University of Nottingham in the United Kingdom, who has pushed to have endangered species included on the list.

    Sequencing challenges

    But waiting might be a good idea. So-called next-generation technologies have revolutionized sequencing during the past few years, providing cost and time savings (Science, 17 March 2006, p. 1544). But there have been tradeoffs: Efficiency brought a shorter “read length”—the number of consecutive bases that can be sequenced—and lower accuracy for each base determined. The accuracy can be compensated for by sequencing the genome multiple times to detect errors. Short reads aren't much of a problem for human DNA, because the existing reference human genome can help sort out where these bits of sequence belong. But assembling large genomes from scratch is quite a challenge.

    CREDIT: ANDREW C. BENTLEY/BIODIVERSITY RESEARCH CENTER/UNIVERISTY OF KANSAS; SOURCE: ADAPTED FROM GENOME 10K COMMUNITY OF SCIENTISTS

    Undaunted, about a dozen groups are pushing the limits of the new technologies, taking a variety of approaches, with varying degrees of success. “We're trying to figure out how to best do this,” says Richard Wilson, director of the Genome Sequencing Center at Washington University School of Medicine in St. Louis, Missouri. Right now, there's a penalty for using cheaper methods: The least expensive sequencer generates the shortest reads, which are the hardest to assemble. Illumina technology produces a base of sequence for about one-tenth the cost of Roche 454 technology, but 454 has the advantage of generating reads about 350 bases long compared with Illumina's 75 bases.

    When they tackled the cod genome in late 2008, Kjetill Jakobsen, a genomicist at the University of Oslo, and his colleagues used Roche 454. It took several months using two machines to generate the bulk of the 750-million-base cod sequence, covering the genome 30 times over. When they were done, “we used brute force,” relying on extensive computing power to put the pieces together, says Jakobsen. The price to sequence: $500,000.

    At least two sequencing centers have bet that they can sequence large genomes even with Illumina's very short reads. In January, the Beijing Genomics Institute in Shenzhen announced that in a month it generated 150 billion bases and stitched them together into a 3-billion-base genome of the Olympic mascot, a panda. They came up with their own computer program for assembling the genome, and the draft consisted of thousands of pieces averaging 300,000 bases long.

    The Broad Institute in Cambridge, Massachusetts, has assembled the stickleback genome sequence this way and is now working on the bush baby. “We've believed in this concept for a while, even when people thought it was crazy,” says the Broad Institute's Chad Nusbaum, who more than a year ago showed that bacterial and fungal genome sequences were doable with short reads. For large genomes, “it's not solved yet, but there are enough indications that it is going to work that we're convinced this is the way to go.”

    Several teams are using a mix of sequencing technologies, hoping this hybrid approach will boost accuracy and efficiency. As Washington University School of Medicine starts the vervet monkey, it expects to use both Illumina and 454 machines and to rely on the traditional capillary-sequencing technology used on the human genome for sequencing the ends of 100,000-base bacterial artificial chromosomes representing the monkey's genome. “For mammalian-sized genomes, that's going to be very helpful,” says Wilson. Richard Gibbs of Baylor College of Medicine in Houston, Texas, has adopted a similar strategy for the baboon. That hybrid approach can speed up finishing, “but it's not a knock-it-out-of-the-park solution,” Gibbs points out. “Difficult sequence is always difficult sequence.”

    Other potentially revolutionary tools could be on the market in the coming year. For example, the Menlo Park, California–based Pacific Biosciences is working on a technology that tracks the enzyme that puts DNA together, noting each new base added. It can sequence two to five bases per second, says the company's Stephen Turner. Last February, he reported read lengths of 3000 bases. “We're absolutely going after the de novo assembly market,” says Turner.

    Wishful thinking?

    Even with all the advances, “the technology isn't there yet” for the kind of sequencing envisioned by Genome 10K, says Adam Felsenfeld of NHGRI. O'Brien, Haussler, and Ryder agree. They need the price tag to drop to $2500 for sequencing a large genome. Their goal is to spend $50 million for the whole project.

    Coming up with the cash could be a challenge. Murphy, Haussler, and O'Brien, among others, hope private philanthropists will foot the bill. Hanotte is calling for public funding to ensure the unrestricted access to the data. Venkatesh thinks funding agencies that support biological, conservation, or biodiversity research will chip in. But NHGRI, which has supported much of the sequencing of large genomes in the United States, is noncommittal. “I don't know how much we will see it fitting in with our priorities,” says Felsenfeld.

    Furthermore, although Felsenfeld and others applaud Genome 10K for identifying tissue sources early, bioinformaticists are worried that insufficient attention has been paid to data management for the assembly and analysis of sequences. To assemble 10,000 genomes in 5 years as proposed will require processing a genome a day, warns Webb Miller, a computer scientist at Pennsylvania State University, State College. “There's a real problem here,” he notes.

    Despite large gaps in their plan, the Genome 10K leaders are supported by an enthusiastic cadre of peers. Participants at the April meeting and their colleagues are busy checking out the samples and deciding which ones have top priority. “We've got real momentum now,” says Haussler. He hopes to do a pilot study demonstrating that these samples are suitable DNA sources for sequencing. Sooner or later, those genomes will be sequenced, Turner predicts. “I don't think it's a question of ‘if’ but ‘when.’ ”

Log in to view full text

Log in through your institution

Log in through your institution