News this Week

Science  23 Nov 2007:
Vol. 318, Issue 5854, pp. 1224

    Field Leaps Forward With New Stem Cell Advances

    1. Gretchen Vogel,
    2. Constance Holden

    For a year and a half, stem cell researchers around the world have been racing toward a common goal: to reprogram human skin cells directly into cells that look and act like embryonic stem (ES) cells. Such a recipe would not need human embryos or oocytes to generate patient-specific stem cells—and therefore could bypass the ethical and political debates that have surrounded the field for the past decade.

    The pace was set in June 2006, when Shinya Yamanaka of Kyoto University in Japan reported that his group had managed the feat in mice by inserting four genes into cells taken from their tails (Science, 7 July 2006, p. 27). Those genes are normally switched off after embryonic cells differentiate into the various cell types. The pace picked up in June this year, when Yamanaka and another group showed that the cells were truly pluripotent (Science, 8 June, p. 1404).

    Now the race has ended in a tie, with an extra twist: Two groups report this week that they have reprogrammed human skin cells into so-called induced pluripotent cells (iPCs), but each uses a slightly different combination of genes. In a paper published online in Cell on 20 November, Yamanaka and his colleagues report that their mouse technique works with human cells as well. And in a paper published at the same time online in Science (, James Thomson of the University of Wisconsin, Madison, and his colleagues report success in reprogramming human cells, again by inserting just four genes, but two of the genes are different from those Yamanaka uses.

    Among stem cell scientists, the human cell reprogramming feats have somewhat overshadowed another major advance reported online in Nature last week: A team at the Oregon National Primate Research Center has officially become the first to obtain embryonic stem cells from cloned primate embryos, an advance that brings therapeutic cloning closer to reality for humans. Taken together, these feats suggest that scientists are getting very close to uncovering the secret of just what occurs in an oocyte to turn back the clock in the DNA of a differentiated cell.

    The two human reprogramming papers could help solve some of the long-standing political and ethical fights about stem cells and cloning. The technique produces pluripotent cells, cells with the potential to become any cell type in the body, without involving either embryos or oocytes—two sticking points that have made embryonic stem cell research so controversial. Ian Wilmut of the University of Edinburgh, U.K., says that once he learned of Yamanaka's mouse work, his lab set aside its plans to work on human nuclear transfer experiments, otherwise known as research cloning. The new work now confirms that decision, he says. Direct reprogramming to iPCs “is so much more practical” than nuclear transfer, he says.

    Full of potential.

    Human induced pluripotent cells form teratomas, tumors with multiple cell types.


    In the new work, Yamanaka and his colleagues used a retrovirus to ferry into adult cells the same four genes they had previously employed to reprogram mouse cells: OCT3/4, SOX2, KLF4, and c-MYC. They reprogrammed cells taken from the facial skin of a 36-year-old woman and from the connective tissue of a 69-year-old man. Roughly one iPC cell line was produced for every 5000 cells they treated with the technique, an efficiency that enabled them to produce several cell lines from each experiment.

    Thomson says he and his colleagues already had their own list of 14 candidate reprogramming genes when Yamanaka's mouse results were published. They, like Yamanaka's group, gradually whittled down the list through a systematic process of elimination. Thomson's experiments led to four factors as well: OCT3 and SOX2, as Yamanaka used, and two different genes, NANOG and LIN28. NANOG is another gene associated with ES cells, and LIN28 is a factor that seems to be involved in processing messenger RNA.

    Instead of cells from adults, Thomson and his team reprogrammed cells from fetal skin and from the foreskin of a newborn boy. But Thomson says they are working on experiments with older cells, which so far look promising. Their experiments reprogrammed about one in 10,000 cells. The efficiency is less than that of Yamanaka's technique, Thomson says, but is still enough to create several cell lines from a single experiment.

    Comparing the two techniques might help scientists learn how the inserted genes work to turn back the developmental clock, Yamanaka says. He says his team tried using NANOG but saw no effect, and LIN28 was not in their initial screen. Thomson says his team tried Yamanaka's four genes without success, but that they may have tried the wrong relative doses.

    The fact that Thomson's suite doesn't include a known cancer-causing gene is a bonus, says Wilmut. (The c-MYC Yamanaka used is an oncogene.) But both techniques still result in induced cells that carry multiple copies of the retroviruses used to insert the genes. Those could easily lead to mutations that might cause tumors in tissues grown from the cells. The crucial next step, everyone agrees, is to find a way to reprogram cells by switching on the genes rather than inserting new copies. “It's almost inconceivable at the pace this science is moving that we won't find a way to do this without oncogenes or retroviruses,” says stem cell researcher Douglas Melton of Harvard University. “It is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes” and produce reprogrammed cells without genetic alterations, he says.

    Although the cells “act just like human ES cells,” Thomson says, there are some differences between the cell types. Yamanaka's group reports that overall human iPC gene expression is very similar, but not identical, to human ES cell gene expression. “It will be probably a few years before we really understand these cells as well as we understand ES cells,” Thomson says. But “for drug screening, they're already terribly useful. IVF embryos are very skewed ethnically,” he says. But with the new iPC technique, “you can isolate cell lines that represent the genetic diversity of the United States. And I think it will be very straightforward to do.”

    The primate cloning success, although partially eclipsed by the human work, “is really a breakthrough,” says primate stem cell researcher Jose Cibelli of Michigan State University in East Lansing. Although scientists have cloned a host of other animals, primates have proved to be particularly resistant—as demonstrated by the failure of Korean scientist Woo Suk Hwang, whose work with human embryos was shown to be fraudulent 2 years ago.


    A group headed by Shoukhrat Mitalipov was able to generate two embryonic stem cell lines after injecting skin cells from a 9-year-old male rhesus macaque into 304 eggs collected from 14 female macaques. The cells showed all the requisite pluripotent stem cell markers; in lab dishes, they generated heart and brain neurons, and in live mice they formed teratomas—tumor tissues from all three germ layers.

    Scientists such as Robin Lovell-Badge of the U.K. Medical Research Council have lauded the feat while pointing out that the low success rate—0.7%—means more primate work is needed before women should be asked to donate eggs for such research.

    Mitalipov originally reported the achievement last June in Cairns, Australia, at the meeting of the International Society for Stem Cell Research. At the time, he met with some skepticism. Before publishing the paper, Nature took the unprecedented step of asking a group headed by David Cram of Monash University in Clayton, Australia, to be sure the cell lines had the same genotype as the donor of the skin cells. Their report is published in the same issue of Nature, which issued a statement declaring this a prudent step given the importance of the results and “recent history in the cloning field.”

    Scientists have discovered that the big peril in cloning, as the Hwang team ultimately discovered, is that what you may really come up with are parthenotes—that is, early embryos arising solely from the activated oocyte. Parthenotes—less useful than clones because they have only the genes of the egg donors—can result when the spindle containing the nuclear DNA is not completely removed before a foreign nucleus is introduced. The usual technique for locating the spindle is with a dye or ultraviolet light, which the researchers suspected could damage fragile primate oocytes. So instead, the Oregon group used a new noninvasive imaging system called Oosight to locate the spindle, then used a probe to suck it out and replace it with the skin cell. Enucleation of the oocyte is 100% efficient with this technique, said Mitalipov. The scientists also changed the culture medium, eliminating calcium and magnesium, which they believe cause premature activation of the oocyte and failure of the donor nucleus to become properly “remodeled.”

    On target.

    Latest imaging technology clearly shows the egg's nucleus, to be withdrawn by pipette at right. Semos (above), the male macaque whose skin cells made history.


    Although the cloning “efficiency is still low,” Mitalipov said at a press conference, “I believe the technology we developed can be directly applicable to humans.”

    Robert Lanza of Advanced Cell Technology in Worcester, Massachusetts, calls the Oregon paper a “turnaround,” saying that it marks a “recovery for the field,” because the Hwang paper was retracted in January 2006. The next step, says Mitalipov, will be to test cloning for treatment of a disease, something that hitherto has been tried only in the mouse. A likely target is diabetes, says Mitalipov, who plans to inject cloned, genetically modified ES cells into a monkey model of the disease.

    “I cannot emphasize enough how useful these [cloned primate ES] cells will be” for studying other diseases that also affect humans, says Cibelli. Another application, he says, will be to compare the cloned primate ES cells with cells reprogrammed by the methods Yamanaka and Thomson used. “If their method is as good as the oocyte” in reprogramming somatic cells, says Cibelli, “we will be no longer in need of oocytes, and the whole field is going to completely change. People working on ethics will have to find something new to worry about.”


    ALS Trial Raises Questions About Promising Drug

    1. Jennifer Couzin

    Patients on therapy declined more rapidly than those on a placebo.

    An antibiotic long thought to hold promise for treating neurologic diseases failed dramatically in a recent clinical trial; this news has sparked a debate about why the drug flopped and whether the results should be interpreted broadly. In a study of 412 people with amyotrophic lateral sclerosis (ALS), published earlier this month, scientists were startled to find that patients on the drug, minocycline, declined more quickly than those on a placebo. Now clinics are urgently tracking down ALS patients whose physicians have prescribed minocycline off label. Many have been taking the drug—approved in the 1970s to treat certain infections—because animal studies have shown it can slow the course of brain diseases, and some small human trials have suggested that it's safe. That did not appear to be the case here.

    The disappointing outcome may affect new or ongoing trials of minocycline for other conditions, including multiple sclerosis (MS) and Huntington's disease. Researchers leading these trials generally reject the idea that the drug's showing in ALS, published online 1 November in The Lancet Neurology, has much bearing. “We don't really believe that the ALS data adds something, but when it's out there, you have to deal with it,” says neurologist Luanne Metz of the University of Calgary in Canada, who is beginning a study of minocycline in 200 people at risk for MS. She argues that MS is very different from ALS—more autoimmune than neurodegenerative—and unlikely to respond in the same way. Still, Metz's trial has added extra safety monitoring.

    In contrast, the authors of The Lancet Neurology paper are quite concerned, arguing that their trial “generates the need to reexamine … the justification for other trials of minocycline in patients with neurological disorders.” Over 9 months of treatment, the ALS patients on minocycline declined 25% faster, as measured by a functional rating scale, than did those taking a placebo. But there was no significant difference in death rates between the two groups, and the patients rated quality of life equally, suggesting that the decline was subtle.

    Exactly what went wrong remains a mystery. Merit Cudkowicz, a neurologist at Massachusetts General Hospital in Boston who is running a minocycline trial in 100 patients with Huntington's disease, believes the drug doses in the ALS study were too high, as much as double what she and Metz are using. But Paul Gordon, who led the ALS trial and works as a neurologist at Columbia University and at Hôpital de la Pitie-Salpêtrière in Paris, notes that patients on the higher doses did no worse than those on lower ones, nor did side effects appear to correlate with deterioration. “We're sort of left with scratching our heads,” he says.

    The results are especially confusing because published animal studies suggested that the drug can suppress neuroinflammation and inhibit cell death. But Gordon notes that mouse studies didn't really reflect the way ALS patients are treated. For example, the mice received minocycline before they began showing symptoms.

    Animal experiments offer only a rough guide to human testing, says neurologist Nigel Leigh of King's College London, who still hopes that minocycline will prove useful for ALS. Leigh says it's possible that high doses of the antibiotic were neurotoxic for patients, whereas lower doses might be neuroprotective. He'd been planning with colleagues to launch a minocycline study in 1000 ALS patients; now he's seeking approval for a revised proposal to identify an ideal minocycline dose in a smaller group of patients.

    “It would be hasty to stop every trial” testing the drug, agrees John Marler, an associate director for clinical trials at the U.S. National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. Even very brief trials of minocycline, though, will consider whether to modify their protocols, says Marler, such as a 3-day acute stroke trial recently funded by the institute. Adds Marler: “We're not going to overlook any possible relief” for these patients.


    If You Build It, Will They Come?

    1. Richard Stone

    CHIANG MAI, THAILAND—With an espresso stand, a gift shop, and a misty forest festooned with orchids and red rhododendrons, the 2550-meter summit of Inthanon Mountain lacks the grandeur of Fuji or the towering remoteness of Everest. But new construction atop Thailand's tallest peak is still making a statement: This Southeast Asian nation intends to become a serious player in global astronomy and a regional leader in the field.

    Earlier this year, Thailand began building an observatory complex on Inthanon, about 100 kilometers west of the temple city of Chiang Mai in northern Thailand. The centerpiece of the $40 million program will be a 2.4-meter optical telescope for studying binary stars and searching for extrasolar planets. It will match the size of the largest instrument in mainland Asia—a newly installed 2.4-meter scope at Yunnan Observatory in Kunming, China, that is about to undergo a year of testing—and serve astronomers from across Southeast Asia and beyond. “It's a bold vision,” says John Hearnshaw, an astronomer at the University of Canterbury in Christchurch, New Zealand, who assessed Thailand's ambitions on behalf of the International Astronomical Union.

    Not everyone is enamored with the project, which is expected to be completed in March 2009. Some scientists have questioned such a large investment in astronomy by a country struggling to build capacity in biology and other fields more tightly coupled to economic growth. Others assail the telescope itself. “People in their right mind would not invest a huge sum of money to build an optical telescope in a tropical area with high humidity,” says one Thai astronomer, who dismisses the project as “a white elephant.”

    Hearnshaw defends the decision. “Certainly the rainy season will curtail the observing season,” he says. “But that won't be a disaster.” He predicts that observing “should be reasonably good” for 9 months a year and that the telescope will be a valuable addition in tracking sudden events like gamma ray bursts and supernovae. “Many of the most exciting discoveries of the last 25 years in optical astronomy have come from small to medium telescopes on the ground,” Hearnshaw says.

    Thailand is home to only about a dozen research astronomers. Even so, the new telescope, to be dedicated to King Bhumibol Adulyadej, the world's longest serving head of state, won't be the first major astronomical facility on the mountain. Earlier this year, three universities—Mahidol, Chulalongkorn, and Ubon Rajathanee—used equipment donated by Japan's Shinshu University to build a cosmic-ray detector at a unique spot in Earth's geomagnetic profile.

    Ad astra per aspera.

    (Above) Boonrucksar Soonthornthum visits Yunnan Observatory to arrange Thai collaboration on China's new 2.4-meter telescope. (Inset) A dormitory for scientists takes shape in Thailand.


    The neutron monitor is named after Princess Maha Chakri Sirindhorn, an astronomy buff, and situated on the grounds of a Royal Thai Air Force radar installation adjacent to the 2.4-meter telescope site. It studies solar cycles and serves as a space-weather sentinel. The geomagnetic equator passes through Thailand, and Earth's magnetic field bulges toward Southeast Asia, producing the strongest horizontal magnetic field on the planet. That dynamo allows only the toughest cosmic particles through. “Our station is registering the most energetic cosmic rays of any neutron monitor in the world,” says astrophysicist David Ruffolo of Mahidol University in Bangkok. Such sensitivity, his group has shown, could provide a 4-hour warning of an oncoming geomagnetic storm—more than twice the lead time of space-weather satellites.

    Four years ago, the Thai government requested proposals to commemorate King Bhumibol's 80th birthday this month. Astronomer Boonrucksar Soonthornthum, who has labored to raise education standards and the country's profile in the international astronomical community, noted that the monarch liked to stargaze in his youth and that a star map graces a ceiling in his palace. Earlier this year, the Thai cabinet approved the National Astronomical Research Institute of Thailand (NARIT) as the sole science megaproject to mark the birthday. NARIT commissioned a $7.8 million telescope from EOS in Canberra, Australia. Construction of NARIT's training center—dormitories for scientists, conference facilities, and an educational display—is in full swing.

    Although first light will occur long after the birthday bash, Boonrucksar's outfit has found another way to celebrate. Next week, NARIT will host an International Olympiad here in astronomy and astrophysics. Some two dozen countries have agreed to send teams of five high school students.

    Boonrucksar sees the Olympiad as part of a larger effort to “teach young people how to think critically and analytically.” That's also the goal behind funding four graduate fellowships a year in astronomy, for study abroad, as part of the telescope project. Thailand hopes to lure foreign talent, too. Expanding the ranks of astronomers “is certainly necessary if the investment in the telescope is to be justified,” Hearnshaw says.

    Boonrucksar deserves credit for succeeding “against all odds” in putting Thailand on the astronomical map, says cosmologist Burin Gumjudpai of Naresuan University in Phitsanulok, Thailand. “It gives us hope,” he says, “that astronomy can be a real career here.”


    More Bumps on the Road to Global Sharing of H5N1 Samples

    1. Martin Enserink,
    2. Dennis Normile

    Indonesia has had the world's greatest number of H5N1 deaths, even while the country flip-flops on sharing flu samples with the World Health Organization.


    A battle between Indonesia and the World Health Organization (WHO) is escalating. Indonesia's health minister, Siti Fadilah Supari, has claimed that WHO is refusing to return dozens of H5N1 influenza viruses isolated from Indonesian samples. WHO calls the claims baseless and says Indonesia can get back the viruses once it shows it can handle them safely. The clash promised to complicate what was already expected to be a difficult international meeting about pandemic preparedness, slated to start in Geneva, Switzerland, this week, after Science went to press.

    At issue are 56 specimens from human H5N1 victims that Indonesia has shared with WHO as part of the Global Influenza Surveillance Network over the past few years. As usual, the samples have gone to WHO's four Collaborating Centres in London, Atlanta, Tokyo, and Melbourne, where researchers isolate and study the virus. Their analysis helps WHO monitor virus evolution, drug resistance, and pandemic risk, as well as aiding vaccine development. Indonesia, by far the most heavily afflicted country with 113 human cases and 91 deaths, has protested the scheme; the country worries that even if it collaborates, it will not have access to vaccines if a pandemic occurs. So far in 2007, Indonesia has shared only two samples, says David Heymann, who heads WHO's pandemic influenza efforts.

    Heymann says that at Supari's request, on 31 October WHO sent Indonesia a list of the 56 specimens the country had submitted to the network prior to 2007. He says the four labs had isolated H5N1 virus from 40 of them. But according to a report in the Jakarta Post, Supari said at a press conference in Jakarta on 8 November that WHO refuses to send the samples back. “We keep asking [WHO] to return the samples because they belong to us. This is for the sake of our country's sovereignty,” the newspaper quoted Supari as saying. Health ministry officials could not be reached to confirm the report. Heymann claims Supari is trying to cast WHO in a bad light. “She has always said she doesn't trust WHO, and she's finding new reasons not to trust us,” he says.

    Masato Tashiro, director of the WHO Collaborating Centre for Reference and Research on Influenza in Tokyo, says he believes Indonesia did not retain part of the samples, as countries usually do, because it previously did not have the biosafety level 3 (BSL-3) laboratories recommended for handling dangerous pathogens. Indonesia had cooperated with WHO's flu-sharing network until early this year when it learned that an Australian company had developed a vaccine using an Indonesian H5N1 strain. Fearing that such a vaccine made outside the country would be out of reach financially, Indonesia started developing its own research and development capabilities while withholding specimens and demanding capacity-building assistance from the international community. Tashiro says that when the institutions requesting viruses can certify that their planned BSL-3 labs are up and running, getting viruses returned from Japan—and probably other countries—would be routine.

    Although Indonesia is the only country that has stopped sending samples, it is reportedly trying to persuade others to follow course. Widjaja Lukito, a physician at the University of Indonesia in Jakarta and a member of Indonesia's delegation to the Geneva meeting, says Indonesia would “clarify everything” in Geneva. Heymann and others say any interruption of the 55-year-old sharing system would create a huge risk for global health.


    How Urgent Is Climate Change?

    1. Richard A. Kerr

    Having issued their fair and balanced consensus document, many climate scientists now cite oft-overlooked reasons for immediate and forceful action to curb global warming

    A goner?

    Time may have run out to prevent the disappearance of summertime Arctic sea ice.


    The latest reports from the nobel Prize-winning Intergovernmental Panel on Climate Change (IPCC) were informative enough. Humans are messing with climate and will, sooner or later, get burned if they keep it up. But just how urgent is this global warming business?

    IPCC wasn't at all clear on that, at least not in its summary reports. In the absence of forthright guidance from the scientific community, news about melting ice and starving polar bears has stoked the public climate frenzy of the past couple of years. Climate researchers, on the other hand, prefer science to headlines when considering just how imminent the coming climate crunch might be. With a chance to digest the detailed IPCC products that are now available (, many scientists are more convinced than ever that immediate action is required. The time to start “is right now,” says climate modeler Gerald Meehl of the National Center for Atmospheric Research in Boulder, Colorado. “We can't wait any longer.”

    What worries these researchers is the prospect that we've started a slow-moving but relentless avalanche of change. A warming may well arrive by mid-century that would not only do immediate grievous harm—such as increase drought in vulnerable areas—but also commit the world to delayed and even more severe damage such as many meters of sea-level rise. The system has built-in time lags. Ice sheets take centuries to melt after a warming. The atmosphere takes decades to be warmed by today's greenhouse gas emissions. And then there are the decades-long lags involved in working through the political system and changing the world energy economy. “If you want to be able to head off a few trillions of [dollars of climate] damages per year a few decades out,” says glaciologist Richard Alley of Pennsylvania State University in State College, “you need to start now.”

    Bad things, soon

    The disturbing message on the timing of global warming's effects comes in the IPCC chapters and technical summaries quietly posted online months after each of three working groups released a much-publicized Summary for Policymakers (SPM). An overall synthesis of the working group reports was released Saturday at the 27th session of IPCC. Earlier this year, only the SPMs went through the wringer of word-by-word negotiations with governments, which squeezed out a crucial table and part of another (Science, 13 April, p. 188). That information—which was always in the full reports—along with other report material, makes it clear that substantial impacts are likely to arrive sooner rather than later.

    Early target.

    Some mountain-dwelling amphibians are already feeling the heat.


    Table TS.3 of Working Group II's technical summary, for example, lays out projected warmings. The uncertainties are obvious. Decades ahead, models don't agree on the amount of warming from a given amount of greenhouse gas, and no one can tell which of a half-dozen emission scenarios—from unbridled greenhouse-gas production to severe restraint—will be closest to reality. But this table strongly suggests that a middle-of-the-road, business-as-usual scenario would likely lead to a 2°C warming by about the middle of this century.

    Lined up beneath the projected warmings in the table are the anticipated effects of each warming. Beneath a mid-century, 2°C warming is a litany of daunting ill effects that had previously had no clear timing attached to them: increasing drought in mid-latitudes and semiarid low latitudes, placing 1 billion to 2 billion additional people under increased water stress; most corals bleached, with widespread coral mortality following within a few decades; and decreases in low-latitude crop productivity, as in wheat and maize in India and rice in China, among other pervasive impacts.

    At the bottom of the same table is a category of effects labeled “Singular Events,” most dramatically sea level rise. The table shows a “Long term commitment to several metres of sea-level rise due to ice sheet loss” falling between the middle-of-the-road 2°C warming and a 3°C warming, which without drastic emissions reductions might well come by the end of the century. The report calls it a “commitment” because although the temperatures needed to melt much of the Greenland ice sheet might be reached in the next 50 to 100 years, the ice sheet, similar to an ice cube sitting on a countertop, will take time to melt even after the surrounding air is warm enough. Its huge thermal inertia means a lag of at least several centuries before it would largely melt away, flooding much of South Florida, Bangladesh, and major coastal cities.

    A laggard system

    Ice sheets aren't the only thing that stretches out the time between an action—say, building a coal-fired power plant—and a global warming impact. For example, the atmosphere is slow to warm because the oceans are absorbing some of the heat trapped by the strengthening greenhouse. IPCC estimates that even if no greenhouse gases were added after the year 2000, the oceans'heat would warm the atmosphere 0.6°C by the end of the century, or as much as it warmed in the last century. So the world is already committed to almost one-quarter of the warming that can be expected late in the century. And half the warming of the next couple of decades will be carried over from emissions in the past century.

    Then there are the lags that come into play ahead of the climate system. The technological infrastructure that does most of the emitting—the gasoline-fed cars and coal-fired power plants, primarily—will have to be radically altered if greenhouse emissions are to be drastically reduced. The speed at which infrastructure can be changed depends on the perceived urgency, says energy-climate analyst James Edmonds of the Pacific Northwest National Laboratory's office in College Park, Maryland. Past transitions from one energy source to another—say, wood to coal—took upward of 50 to 100 years, he notes. But even with a Manhattan Project imperative—something nowhere in sight—weaning cars off oil, building nuclear power plants, and rigging coal power plants to shoot the carbon dioxide into the ground will take decades, not years.

    And there's the lag while governments crank up the will to fundamentally alter the global energy system. “The biggest lag is in the political system,” says geoscientist Michael Oppenheimer of Princeton University. A couple of decades have already passed discussing the seriousness of the threat, as he sees it, and at the present rate it could be another 20 years before a worldwide program up to the task is in place.

    Yet another lag would enter the calculation for taking action if policymakers waited for more research to narrow the scientific uncertainties. In the 1980s, for example, the biggest uncertainty in climate science was clouds and how they would react to climate change. Fifteen years later, “we are essentially where we were then,” says atmospheric scientist Robert Charlson of the University of Washington, Seattle. Clouds are still poorly understood, as are pollutant hazes, another collection of microscopic particles with a highly uncertain effect on future climate.


    With all these known time lags adding up to many decades, a lot of climate scientists say that the time for serious action is now. “We can't really afford to do a ‘wait and learn’ policy,” says Oppenheimer. “The most important question is, when do we commit to 2°? Really, there isn't a lot of headroom left. We better get cracking.”

    Fear of the unknown

    Physics and socioeconomics may make piloting the ponderous ship of climate a cumbersome business, but researchers are also worried about navigating around the hazards they fear may be lurking unseen beneath the surface. They've hit hidden obstacles before. Back in the 1970s, atmospheric chemists were worrying that pollutant chlorine might be destroying stratospheric ozone over their heads. Yet all the while, that chlorine was teaming up with ice-cloud particles over Antarctica to wipe out stratospheric ozone through a mechanism that scientists had overlooked.

    Prestigious committees have been warning for 25 years that similar surprises could spring from the climate system. A few may be starting to show themselves. Arctic sea ice took a nosedive last summer, prompting concerns that feedbacks not properly included in models are taking hold and accelerating ice loss (Science, 5 October, p. 33). Glaciers draining both southern Greenland and West Antarctic have suddenly begun rushing to the sea, and glaciologists aren't sure why (Science, 24 March 2006, p. 1698). And theorists recently reminded their colleagues that they will never be able to eliminate the small but very real chance that the climate system—contrary to most modeling—is hypersensitive to greenhouse gases.

    The uncertainties are adding up. “You can hope the uncertainties are going to break your way,” says policy analyst Roger Pielke Jr. of the University of Colorado, Boulder. “There have been times they did. But if you play that game often enough, you're going to lose some pretty big bets sometimes.” In the case of global warming, Pielke says, “we don't have a lot of time to wait around.” Edmonds agrees. If avoiding a 2°C warming is the goal, “the world really has to get its act together pretty damn fast. The current pace isn't going to do it.”


    The B Cell Slayer

    1. Robert Matthews*
    1. Robert Matthews is a freelance writer based in Oxford, U.K.

    It took nearly a decade for Jonathan Edwards to persuade people that killing B cells could relieve symptoms of rheumatoid arthritis. Multiple sclerosis is his next target

    B gone.

    Killing B cells (left) could be a treatment for autoimmune diseases.


    LONDON—For someone who has just seen his ideas for treating a crippling disease vindicated after years of rejection, Jonathan Edwards is remarkably self-effacing. Asked whether he feels he has brought hope to some of the millions with rheumatoid arthritis (RA), the 57-year-old rheumatologist tends to look at his shoes or up at the ceiling. Edwards would much rather talk about where he plans to go next than to dwell on how his University College London (UCL) team's decade-long pursuit of an unfashionable idea has now led to a new RA therapy approved in the United States and in Europe.

    The unfashionable idea advocated by Edwards is that RA stems from the misbehavior of denizens of the bloodstream known as B cells. These white blood cells play a key role in the body's immune system, releasing disease-fighting antibodies that have exquisite specificity for molecular targets, normally those on pathogens. B cells are also obvious suspects in autoimmune conditions such as RA, in which the immune system goes haywire and starts unleashing friendly fire within normal healthy tissue. Yet the idea of their involvement fell out of favor in the 1970s when autoimmune researchers interested in RA turned their attention to a different white blood cell, the T cell.

    Edwards, however, has breathed new life into the B cell theory of RA by providing evidence that eliminating these cells in patients can ease their symptoms. “Edwards deserves great personal credit; … he was a strong, consistent voice at a time when most others were not looking at B cells as central to rheumatoid arthritis pathogenesis,” says rheumatologist Gregg Silverman of the University of California, San Diego.

    B cell-depletion therapy doesn't work for every RA patient, and questions remain about how long the relief it brings lasts. Still, once again challenging conventional wisdom, Edwards is now arguing that B cells hold the key to another autoimmune affliction: multiple sclerosis (MS). And there is already tantalizing clinical evidence that the outcome could be the same—namely, a new therapy for a notoriously recalcitrant disease.

    The return of B cells

    When Edwards began his career in rheumatology in the 1970s, B cells seemed a prime suspect in the cause of RA, as they are the source of so-called rheumatoid factor (RF), a variety of antibody found in high levels in patients with the disease. Yet about 20% of RA patients don't have RF in their blood, and the level of RF doesn't correlate perfectly with the severity of disease.

    As researchers struggled to link B cells with what they were seeing in their patients, attention shifted to the behavior of T cells instead. These white blood cells help control B cells and turn up in joint tissue damaged by RA in larger quantities than B cells do. “By the late 1970s, B cells didn't seem to have anything to say. They'd become boring,” says Edwards. T cells “were just much more interesting.”

    For the next 20 years, T cells dominated the research agenda on autoimmune diseases. Yet it became clear, at least to Edwards, that the excitement about T cells was largely misplaced. Anti-T cell therapies failed to work for RA. It also remained unclear that T cells could cause inflammation without the involvement of B cells. Nor, he argued, could T cells account for the persistence of RA.

    All this prompted Edwards and his UCL colleague Geraldine Cambridge to begin pondering alternatives in the late 1990s—including the old idea that B cells held the key to therapy. The pair had been struck by the discovery that joint tissue attacked in RA contained two molecules—VCAM-1 and DAF—known to promote the persistence of B cells.

    By 1998, Edwards and Cambridge had the framework of a new explanation for RA based on B cells. Put simply, they suspected that the problem was a few bad apples. The body maintains a vast array of B cells, each producing an antibody with a unique shape, many of which prove useful in fighting disease. By chance, however, some B cells inadvertently produce antibodies that attack healthy tissue. Normally, the B cells producing these “autoantibodies” are destroyed. But in a disastrous twist in some people, the UCL team proposed, some of these autoantibodies undermine the weeding-out process, keeping the bad-apple B cells alive and also prompting T cells to help these B cells make yet more of their destructive antibodies. “The result is a vicious cycle,” says Edwards.

    The test of this hypothesis was obvious: Eliminate B cells from people with RA and let the immune system “reboot” with new B cells. The odds that the same bad apples would arise again and survive weeding out would be very small. As luck would have it, a drug capable of killing B cells but sparing the stem cells that make them had just reached the market. Approved in 1997 for use with B cell lymphomas, rituximab is a monoclonal antibody specially designed to home in on and knock out the immune cells. If Edwards and Cambridge were right, rituximab could also be the basis of a treatment for RA. A largely safe one, moreover: Studies of rituximab in hundreds of cancer patients had produced relatively few side effects and shown that people could temporarily lose all their B cells without suffering too many problems from suppression of their immune systems.

    The pair tried to publish their B cell theory—only to encounter responses from journals ranging from lukewarm to cryogenic. “We were told there was already a perfectly good explanation—based on T cells,” recalls Edwards. “The major medical journals wouldn't take it at all.” Their proposal finally appeared in Immunology in 1999 and provoked no response at all.

    Undeterred, the UCL team set up a pilot trial, giving B cell-depleting drugs, including rituximab, to five people with especially severe RA. Once their B cells disappeared, the patients' symptoms improved dramatically, and three continued to do well even after their B cells returned, 6 months or so later. Although journals dismissed the results on so few patients as inconclusive, Edwards scraped together more money from departmental funds and recruited more patients. At a 2000 meeting, the UCL team was able to present data on 20 patients, all but two of whom had shown major improvements, some for as long as 18 months.

    The media picked up on the apparent success, but the resulting headlines sparked accusations of hype, with the British Medical Journal condemning the “irresponsibility” of the UCL team in talking to the press about preliminary results from such a small trial. Still, Edwards got the support of the drug company Roche, which owns the European rights to rituximab, to push ahead. By 2002, the UCL team had the results of a randomized, controlled trial involving 161 patients, which showed that more than 40% of those receiving rituximab with methotrexate, a conventional anti-inflammatory agent, had experienced major improvements in symptoms at the end of 24 weeks, compared to just 13% of those receiving MTX alone. The relief continued even when the patients were checked 48 weeks after the B cell-depletion therapy. “When I presented these results, I think the penny finally dropped within the research community,” says Edwards. Indeed, The New England Journal of Medicine ultimately published the study's results in 2004.

    The success prompted further, larger trials, and last year, the regulatory authorities in both the United States and Europe approved rituximab for use with MTX in severe cases of RA. And in August, the United Kingdom concluded that the therapy was sufficiently cost-effective to be made available free of charge through the National Health Service.

    RA patient groups are understandably delighted about the new therapy, with the U.K. charity Arthritis Care describing it as “a triumph.” The RA research community is also excited. “I grew up thinking rheumatoid arthritis was a kind of classic B cell disease, and then the T cell people moved in,” says Alan Silman of the University of Manchester, U.K., who is medical director of the U.K. Arthritis Research Campaign. “Edwards put B cells back on the agenda.”

    Seeking approval.

    Jonathan Edwards's efforts resulted in B cell-depletion therapy being approved for rheumatoid arthritis.


    Remaining doubts, new disease

    Yet Silman isn't totally won over. He and others continue to argue that most of RA's inflammation is caused by a direct effect of T cells. “B cells don't correlate perfectly with the disease,” says Silman.

    There have also been new safety concerns about rituximab, as two lupus patients receiving the drug last year died of a rare viral infection. But no link with the drug has been proven. Overall, says Silverman, almost a decade of rituximab use has shown the drug to have a good safety profile, with no increase in opportunistic infections among those receiving it.

    Edwards accepts that questions remain about the role of B cells in RA: Why do fewer than half of patients respond to rituximab, for example? Nevertheless, Edwards and his colleagues have become interested in whether B cell-depletion therapy can treat MS, a neurodegenerative condition stemming from the destruction of the myelin insulation surrounding vital nerve cells. This myelin loss triggers a host of symptoms, from muscle spasms and pain to loss of bladder and speech control.

    Many scientists have argued that T cells drive the myelin breakdown in MS, but no effective therapy has yet resulted from pursuing that theory. Edwards notes, however, that studies in the mid-1980s found that in the early stages of MS, the damage to nervous tissue seemed linked to the local accumulation of offspring of B cells known as plasma cells. Indeed, back in 1999, Edwards tried to interest neurologists in testing B cell-depletion therapy on MS patients but found no takers.

    Given the poor prognosis of many people with MS and the apparently low risks involved in rebooting the B cell system, Edwards has continued to lobby that rituximab is worth a try. And some MS researchers have started to agree. “There's strong circumstantial evidence implicating antibodies” and thus B cells in MS, says immunologist Christopher Linington of the University of Aberdeen, U.K. “Rituximab will almost certainly help some patients. The problem is, you cannot predict which ones.”

    In May at a neurology meeting, a team at the University of California, San Francisco (UCSF), unveiled preliminary results from an ongoing rituximab trial involving more than 100 patients with so-called remittingrelapsing MS. The data, primarily magnetic resonance imaging scans of the patients' nervous systems, indicated that the drug has dramatically reduced the nerve damage caused by the disease. “It's no longer a question of ‘Do B cells contribute to MS?’” but rather how, says Amit Bar-Or of McGill University in Montreal, Canada, who worked with the UCSF team assessing the safety of the potential new therapy.

    The UCL team is playing down any suggestion that they've been proved right again. Edwards says it's far too early for that, although he's hopeful. “The longer we stay in this business, the more we realize there may be further twists to the tale,” he says.


    Cell Biology Meets Rolfing

    1. David Grimm

    A diverse group of researchers wants to create a new discipline from scratch by bringing together experts in fascia and deep-tissue massage

    BOSTON—Peter Huijing was far from enthusiastic when he received an invitation to speak at the Fascia Research Congress. The meeting, held here last month, would be the first dedicated to the soft part of the body's connective tissue system—an important but medically neglected organ. It would bring together top scientists from fields as diverse as cell biology and biophysics, but it would also include alternative medicine practitioners, such as chiropractors and deep-tissue manipulators known as Rolfers. “I had a fear of damaging my reputation,” says Huijing, a world-renowned biomechanics researcher at Vrije Universiteit in Amsterdam, the Netherlands, who, despite his hesitation, decided to attend. By the time the conference was over, Huijing had agreed to organize the next one.

    The conference was the brainchild of Thomas Findley, an M.D.-Ph.D. co-director of research at the VA Medical Center in East Orange, New Jersey. For 30 years, Findley has been studying the science behind rehabilitation medicine; he is also director of research at the Rolf Institute of Structural Integration in Boulder, Colorado, which trains and certifies Rolfers. He became convinced early on that fascia—which weaves its way through the body like a gossamer blanket, cradling organs, ensheathing bones, and providing structural support—plays a key role in how patients respond to treatment. He wanted to learn more, but there were no identifiable fascia researchers.

    Frustrated, Findley began e-mailing scientists like Huijing in 2005. He knew that researchers around the world had been studying fascia in some form—MEDLINE references to i t have spiked in the past 3 years—but that they didn't see themselves as part of a coherent field. Huijing, for example, looks at how the body generates force via the interactions between muscles and fascia, but he was unaware of cell biologists who were studying how fascial cells respond to movement. Findley hoped that bringing such scientists together would stimulate new research collaborations and shed light on the mysterious tissue.


    Fascia shown here is from a lower leg muscle, dissected by Peter Huijing (inset).


    Findley also wanted to bring in clinicians, but he knew that M.D.s wouldn't cut it. Some researchers have speculated that fascial anomalies may be responsible for black box disorders like fibromyalgia and lower back pain, yet doctors have traditionally ignored the tissue. Medical books barely mention fascia, and anatomical displays remove it. “It's just not sexy,” says Elizabeth Montgomery, a pathologist who specializes in soft tissue at Johns Hopkins University in Baltimore, Maryland.

    So Findley turned to the alternative-medicine community. Findley knew that Rolfers and other alternative therapists held fascia in high regard: They believe that rubbing and stretching the tissue brings about the improvements they see in clients.

    Yet they don't have the tools or data to prove their claims. “Practitioners want to know the science behind what they're doing,” says Findley, “and scientists want to see clinical applications of their work.” Combining the two groups to create a new field seemed natural. But as the meeting in Boston revealed, bridging the gap won't be easy.

    The great divide

    Frederick Grinnell picked up on the gap right away when he heard the applause—in the middle of a talk. It was 9:00 in the morning on the first day of the conference, and Paul Standley, a vascular physiologist at the University of Arizona College of Medicine in Phoenix, was describing his work on fibroblasts, the chief type of cell found in fascia. When Standley's team placed the cells on flexible collagen and stretched the collagen in ways that replicated repetitive motion strains on the body, many cells died. But when the team followed the strains by stretching the collagen in ways that approximate techniques like Rolfing, more cells survived. The audience erupted.

    “It's rare to see such enthusiasm at a conference,” says Grinnell, a cell biologist at the University of Texas (UT) Southwestern Medical Center in Dallas. “I was really struck by it.” The audience was composed mostly of alternative-medicine practitioners—chiropractors, massage therapists, and Rolfers—who signed up in droves when Findley first advertised the meeting in the fall of 2006. Within 5 months, the 500-seat venue at Harvard Medical School had sold out.

    The scientists took more convincing. In addition to Findley's aggressive e-mail campaign, a 51-year-old graduate student named Robert Schleip (see sidebar) traveled to labs around the world looking for plenary speakers. Some, like Grinnell, saw the conference as an opportunity to learn from other basic researchers. “I never realized my work on cell mechanics related to tissue mechanics until I heard about this meeting,” he says. But others, like Huijing, were turned off at first: “I had never heard of things like Rolfing before,” he says. “I didn't see the relevance.” In the end, 58 scientists signed up for the meeting—along with 51 M.D.s. Most of them took the podium, whereas the practitioners filled the seats.

    Clapping aside, many of the practitioners struggled with the science. Findley was adamant that the talks not be “watered down,” and intricate presentations on the first day pulled no punches. Cell biologists spoke about how fascial cells alter gene expression in response to force, while biomechanics researchers detailed how interactions between fascial cells and the extracellular matrix contribute to whole body mobility. By the afternoon, the auditorium was noticeably emptier. “My frontal lobe was tired,” says Briah Anson, a St. Paul, Minnesota-based Rolfer.

    For their part, the scientists had some problems connecting with the clinicians. Huijing's fears of stigma seemed to be borne out when he interacted with one group of attendees. “They started talking about aura,” he says. “I don't want my name associated with that.” And Giulio Gabbiani, a cell biologist at the University of Geneva in Switzerland who studies connective tissue and wound healing, acknowledged difficulty discussing some concepts with the practitioners. “It's like we were talking two different languages,” he says.

    All of this prompts Wallace Sampson to question whether putting the two camps together is a good idea. “Fascia is a legitimate target of study, but a field like this has to be generated organically,” says the alternative-medicine skeptic and professor emeritus at Stanford University in Palo Alto, California. “You have to do the basic science and see what evolves. You can't force the clinical side.”

    Partap Khalsa strongly disagrees. “It's not only valid to bring these groups together, it's essential,” says the program officer with the U.S. National Institutes of Health (NIH) National Center for Complementary and Alternative Medicine (NCCAM), which, along with organizations such as the Rolf Institute and the Evanston, Illinois-based Massage Therapy Foundation, provided funding for the meeting. “You need people who can do good basic science and clinicians who can inform them about their experiences,” he says. “It's the only way to advance the field.”

    Bridging the gap

    By the second day of the conference, things began to gel. A clinician-scientist panel fostered a dialogue between the two groups, and a networking lunch sparked new collaborations. “I heard clinicians talking about how manipulating fascial stiffness was key to their interventions,” says UT Southwestern's Grinnell. Now he plans to study the cell biological basis of stiffness and how it might contribute to wound repair and scarring. Huijing says he also learned new things from the alternative therapists—and he found that he had something to teach them as well. Establishing fascia research as a legitimate field, he says, will guarantee that these interactions continue.

    Findley knows it won't be easy. First, he'll need to attract more scientists. Publishing fascia research in top journals would help. He'll also need to cultivate a stable source of funding. Through the Rolf Institute, Findley has helped establish the Ida P. Rolf Research Foundation (named after the institute's founder), which is raising funds in hopes of awarding $200,000 in grants per year in 2 to 3 years. That's still a pittance compared to the millions NIH can provide, and NCCAM's Khalsa says he likes what he saw at the meeting. “There's a lot of potential here,” he says.

    But Findley's greatest challenge will be keeping everyone happy. Practitioners want to see more of their own up on the podium, and scientists want assurances that everything will remain respectable.

    It's a tightrope Huijing looks forward to walking in 2009 when he puts together the next conference, to be held in Amsterdam. Huijing plans to give a larger spotlight to practitioners and to explore even more of the basic science. He's adding days, and he's reserved an auditorium for 1000 people—twice the size of the room at this year's event. “I have a feeling it could be very big,” he says.


    From Rolfer to Researcher

    1. David Grimm

    Robert Schleip remembers the moment he became a “born-again scientist.” For 13 years, he had been teaching Rolfing—a technique that involves rubbing and stretching a bodywide network of soft connective tissue known as fascia—when he began to question his lesson plans. “I found there was a pseudoscientific mentality behind what I was doing,” says Schleip, who in 1978 became Germany's first licensed Rolfer. “I thought, ‘I'd better check this stuff out.’”

    So Schleip turned to the scientific literature on fascia. “When I did my homework, I discovered that some of [the Rolfing dogma] didn't look so good.” For example, as part of their training, Rolfers assume that if they apply enough force to an area of fascia, they can lengthen it and remove tension. “But the science says you would have to apply a ton of pressure to effect these changes,” Schleip says.

    The literature also provided insight: Schleip discovered, for example, that fascia is highly innervated, and that might explain why manipulating the tissue could ease pain. “I knew there were many gold mines waiting,” Schleip says. So he stopped teaching and pursued a scientific career.

    Getting a research position wasn't easy. Ten professors turned Schleip down before one at Ulm University gave him a chance—but no lab space. Schleip spent his first year conducting experiments in his kitchen and in a storage room he rented from a nearby pharmacy. He began to study the ability of fascial tissue to contract—a property that could play a role in stiffness and lower back pain. “The professor was so impressed with how much I did on my own that he let me work in his lab,” Schleip says.

    Sea change.

    Robert Schleip was a prominent Rolfer before he became a scientist.


    Schleip now has a lab of his own. He earned his Ph.D. with honors in 2006 at the age of 52, and shortly thereafter established the Fascia Research Project at Ulm University. He's continuing his work on fascial contraction and has begun collaborating with Giulio Gabbiani, a preeminent cell biologist at the University of Geneva in Switzerland. Now Schleip says that when he calls professors to discuss research projects, they call him back.


    Did Horny Young Dinosaurs Cause Illusion of Separate Species?

    1. Erik Stokstad


    Of all the strange-headed dinosaurs, the prize for toughest, prickliest noggins probably belongs to the pachycephalosaurs—literally, the “thick-headed lizards.” Some sported domed skulls, and all had bony spikes studding their long snouts. Four species are known from roughly 65-million-year-old rocks in Wyoming, Montana, and South Dakota alone. It's an impressive display of diversity for the waning days of the dinosaurs.

    Or maybe not. At the Society of Vertebrate Paleontology's annual meeting here last month, Jack Horner of Montana State University (MSU) in Bozeman argued that three of the species are just one. What were thought to be two unique species, he says, are in fact juveniles of different ages that would have grown up to be bony-headed Pachycephalosaurus. “It's a dramatic remake,” says Peter Dodson of the University of Pennsylvania.

    The revision would remove two particularly colorful characters from the paleontological bestiary, and not everyone is convinced. Getting the taxonomy right has major implications, says David Evans of the Royal Ontario Museum in Toronto: “It's really important for understanding a whole range of evolutionary phenomena.”

    First described in 1931, Pachycephalosaurus wyomingensis has such a prodigious pate that paleontologists speculated males butted heads with each other, although many now doubt it (Science, 5 November 2004, p. 962). In 1983, a related species made its debut. Stygimoloch spinifer (“horned devil from the river of death”) had a smaller dome but fearsome spikes. The newest addition was introduced last year: Dracorex hogwartsia has a flat head with telltale nasal horns. The dragon-king was named in honor of J. K. Rowling, whose Harry Potter novels feature the Hogwarts School of Witchcraft and Wizardry.

    Horner and colleagues—MSU doctoral student Holly Woodward and Mark Goodwin of the University of California, Berkeley—suspected that young dinosaurs might have been misidentified as adults. During previous work on another pachycephalosaur, Stegoceras, they noticed that the bone of smaller specimens was full of radial canals, a spongelike texture that indicates rapidly growing bone and suggests that they were juveniles.

    The team cut open skulls of Pachycephalosaurus and found dense bone without canals, suggesting that the specimens were full-grown adults. Stygimoloch bone was full of canals. “This is not even close to being full-grown,” Horner says. The spikes had a spongy texture and showed signs that the bone was being resorbed—suggesting it was a juvenile Pachycephalosaurus.

    E pluribus unum.

    Three species of pachycephalosaurs may actually be just one that changed drastically during adolescence.


    There is only one specimen of Dracorex, housed in the Children's Museum of Indianapolis, so Horner couldn't cut it open to look at the tissue. Horner notes that little bumps on the top of the head of Dracorex resemble those that give rise to radial bone growth in Stygimoloch. Two large holes in the top of the skull are another characteristic of juveniles that haven't finished growing. Given the lack of a dome and the shorter skull, Horner suspects that Dracorex is an even younger Pachycephalosaurus. He says the hypothesis could be falsified if researchers were to discover, say, a new skull of Dracorex that is as big as Pachycephalosaurus or that has mature bone.

    The argument makes sense to Robert Sullivan of the State Museum of Pennsylvania in Harrisburg, who co-authored a paper describing Dracorex published last year in the New Mexico Museum of Natural History and Science Bulletins. In another talk at the meeting, Sullivan speculated that juvenile pachycephalosaurs in Asia may have been misidentified as new species. But another author, Robert Bakker of the Houston Museum of Natural Science in Texas, adamantly opposes lumping together the three North American species. “The differences are [so] astonishing,” he says, that he can't imagine that one could have grown into the other. Evans, on the other hand, says such big changes are possible. “What dinosaurs teach us is that relative growth can be extreme, particularly in the skull,” he says.

    What's needed are careful measurements of many specimens to see how shape changes with size, Evans says; this can help reveal whether various specimens all belong to a so-called growth series. If some features, such as the height of the dome, do not depend on size, it would suggest they rightly belong to different species. Because juveniles tend to start out with features of their evolutionary ancestors and modify them as they grow, it's important to distinguish juveniles from adults or family trees may get confused. That would give researchers a skewed picture of how various pachycephalosaurs are related to one another and to more distant taxa.

    If Horner turns out to be right, the diversity of pachycephalosaurs would be 50% lower than previously thought for the latest Cretaceous. “It makes a lot more sense,” he says, because other kinds of dinosaurs were also declining in diversity at the time. Not even an honorary degree in wizardry, it seems, was enough to save them.


    Jaw Shows Platypus Goes Way Back

    1. Erik Stokstad



    Ancestors of the duck-billed platypus may have had the same electrosensory bill.


    When scientists first laid eyes on the duckbilled platypus and the echidnas in the late 18th century, they were so baffled by these bizarre egg-laying mammals that some considered the specimens a hoax. Modern researchers have uncovered other implausible features, including 40,000 tiny glands in the broad bill that sense electric currents, which may help the platypus catch prey underwater. The ant-eating echidna has about 100 in its tiny snout. The platypus and echidna are so unusual that they were assigned an order—the Monotremata—separate from the more common marsupial and placental mammals.

    The fossil record of monotremes is also sparse. The oldest known specimen is a single tooth from Patagonia, about 62 million years old, with a distinctive compressed shape like that of juvenile platypuses before they lose their teeth. A reanalysis of fossil jaws from Australia, reported at the meeting, suggests it belonged to a platypus that lived at least 112 million years ago. “It's really, really old for a monotreme,” Timothy Rowe of the University of Texas (UT), Austin, told the audience.

    Teinolophos trusleri was discovered near Inverloch, Australia, in 1997 and described by Thomas Rich of the Museum Victoria in Melbourne, Pat Vickers-Rich of Monash University, and colleagues. The specimens consist of jaws and teeth.

    Grand canal.

    The dark gray area in the CT scan (above) of a jaw marks the path of nerve fibers.


    Looking for more anatomical clues to the evolution of mammals, Rich's team took fossil jaws to Rowe, a paleontologist who also runs a computed tomography-scanning facility at UT Austin. Scans of three specimens revealed a large internal canal along the entire length of the jaw, like the canal in a modern platypus that carries nerve fibers from the electrosensory glands in the bill to the brain. “There's no other mammal that has a canal this size,” Rowe said. Even back in the early Cretaceous, it seems, the platypus was using electrosensation. “This is the most compelling evidence to us that Teinolophos is a platypus.”

    That would push back the fossil record of the platypus quite a bit; the next youngest fossil is Obdurodon dicksoni from 15-million-year-old rocks in Australia. It is also much older than current estimates from DNA of when platypuses and echidnas diverged from their most recent common ancestor. Molecular clocks put that date somewhere between 17 million and 80 million years ago. Rowe speculated that one reason for the underestimate may be that monotremes evolve at slower rates than other mammals do, an idea that fits with their lower diversity.

    Zhe-Xi Luo of the Carnegie Museum of Natural History in Pittsburgh, Pennsylvania, agrees that the canal in Teinolophos resembles that of a modern platypus: “I'm leaning toward accepting Rowe's idea.”


    Snapshots From the Meeting

    1. Erik Stokstad

    Hopping toward frogs. About 340 million years ago, amphibians began to evolve into an amazing array of now-extinct forms. Some grew 3 meters long; others developed armor. One of the most diverse groups, called the Dissorophoidea, also concocted some more familiar shapes that resemble modern amphibians. Jason Anderson of the University of Calgary in Canada described an unnamed fossil that strengthens the case that dissorophoids gave rise to frogs and salamanders.

    The 12-centimeter-long fossil was discovered in Texas in 1995. The nearly complete specimen is housed in the collections of the Smithsonian Institution's National Museum of Natural History. The skull looks froglike enough that the fossil was dubbed “Froggy,” and the number of bones in the digits are also froglike. The short ribs and fused bones in the ankle are like those of salamanders. A classic dissorophoid called Amphibamus had 21 vertebrae, the oldest fossil frog had 14 vertebrae, and Froggy fits in between with 17. All told, Anderson says, Froggy is the closest fossil relative to frogs and salamanders. “It really neatly fills the gap,” says Rainer Schoch of Staatliches Museum für Naturkunde in Stuttgart, Germany.

    Flight first. A stunning new fossil unveiled at the meeting suggests that bats evolved flight before they began to echolocate. “We're all excited about it,” says Nicholas Czaplewski of the Oklahoma Museum of Natural History in Norman. “There's a lot you can learn from a specimen that well preserved.”

    In her presentation, Nancy Simmons of the American Museum of Natural History in New York City described the 52-million-year-old bat, which came from Green River Formation in Wyoming and is now housed in the Royal Ontario Museum in Toronto, Canada. “When we first saw it, we knew it was special,” she recalled. The bat has traits that make it the most primitive yet discovered. For example, there are claws on all five digits; modern bats have claws on at most two fingers of each hand. The claws could have made the bat a skilled climber.

    Long fingers, a keeled sternum, and other features suggest that the bat could flutter under its own power. It probably couldn't fly as far or as fast as other fossil bats, because of the stubby wings, but it would have been able to maneuver well. The skull lacks the features of echolocation, such as an enlarged cochlea, found in modern bats. “It finally gives us an answer: Flying evolved first, echolocation second,” Simmons said.

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