News this Week

Science  10 Jan 2003:
Vol. 299, Issue 5604, pp. 180

    Human Flight Is Next Step for China's Space Program

    1. Ding Yimin,
    2. Dennis Normile*
    1. With reporting by Pallava Bagla in Bangalore, India.

    BEIJING—China is poised to become the third country to launch humans into space after the safe return of its latest craft, which carried instrumented dummies. The recovery of the Shenzhou 4 capsule, which touched down 5 January in northern China after a 7-day flight, sets the stage for a flight later this year by one or two members of China's 12-person corps of “taikonauts.” Space officials said that the latest Shenzhou mission, which carried more than 50 experiments, also demonstrates China's determination to pursue microgravity and life sciences research in space.

    Taking flight.

    China says “taikonauts” will be on board the next launch of its Shenzhou capsule.


    Guo Baozhu, deputy director of the China National Space Administration (CNSA) in Beijing, told an international space summit last week in India that barring unforeseen problems, China will put a human being into space sometime before the end of the year. Guo said that China's human space flight program, which has been managed by the military, “is quite expensive” but that its growing (and classified) budget “has not come at the cost of civilian space programs.”

    The decision to replace the dummies with a live crew will shape which experiments receive priority on future missions. “I assume that the first [human] flight will mainly focus on the safety of astronauts,” says a scientist at the Shanghai Institutes for Biological Sciences who had a payload on Shenzhou 4. “So my fellow scientists and I are not expecting more opportunities on the next flight.” One of the Shanghai institute's experiments monitored the effects of microgravity on the fusion of two cells; another examined the isolation of proteins as a step in space-based drug manufacturing.

    But human flight could be a boon for Hu Wenrui, a physicist at the Chinese Academy of Sciences' Institute of Mechanics in Beijing. He had an experiment aboard Shenzhou 4 and is studying how droplets of one fluid flow through a matrix of a different fluid in microgravity, behavior which he says is critical for space-based materials processing. “I am looking forward to conducting more complicated experiments on future [human] flights,” he says.

    Other experiments aboard an orbiter that will remain in space for several months include a microwave sensor to gather a variety of oceanic data and several detectors to record the impact of high-energy particles on the spacecraft. “We're downloading lots of data,” says Wu Ji, deputy director of the Center for Space Science and Applied Research in Beijing, which coordinates the scientific experiments carried on the Shenzhou missions.

    Xu Yansong, a senior CNSA official, says that China hopes the coming program will lead to new technologies and materials but readily admits that a string of successful missions also “will enhance national prestige.”


    Expert Panel Urges a Boost for Smithsonian Science

    1. Jennifer Couzin

    A special commission told the Smithsonian Institution this week that it needs to bolster its science budget and improve its oversight of basic research. The report, assembled by an independent 18-member group that included six institution scientists, was requested in May 2001 by the Smithsonian's Board of Regents after the institution's new secretary, Lawrence Small, advocated sweeping changes in research programs. In November, a report from the National Research Council lauded the quality of Smithsonian science (Science, 8 November 2002, p. 1157).

    New directions.

    Jeremy Sabloff and his commission offered Smithsonian science a blueprint.


    The new report contains 76 recommendations and few surprises. The regents have already endorsed the 123-page document, which among other things gives some support to Small's contention that the Conservation and Research Center in Front Royal, Virginia, doesn't fit under the Smithsonian umbrella. The report also laments the high turnover in leadership: The National Museum of Natural History, for example, has had 11 directors in the last 22 years.

    “There has not been an overall vision for Smithsonian science,” says commission chair Jeremy Sabloff, director of the University of Pennsylvania Museum of Archaeology and Anthropology in Philadelphia. To improve the focus of research, the review proposes four broad themes: the origin and nature of the universe, the formation and evolution of the planets, discovering and understanding life's diversity, and the study of human diversity and culture. In addition, it urges administrators to improve communication with scientists.

    The panel's biggest concerns were financial. The Smithsonian, which receives 57% of its funds from Congress and most of the rest from philanthropic sources, is struggling to cover basic research expenses even as it carries out $1 billion in new construction projects. The report advocates increased funding from Congress for Smithsonian science and proposes that Smithsonian staff be allowed to apply for federal grants, now largely off-limits.


    New Look at Old Data Irks Smallpox-Eradication Experts

    1. Martin Enserink

    For the past 9 months, Yale University mathematician Edward Kaplan has been a thorn in the side of architects of the U.S. bioterrorism policy, arguing that they are placing too much faith in a strategy called ring vaccination to contain a smallpox epidemic. Now, Kaplan has published a paper that he says deals another blow to that strategy—further raising the ire of his opponents, some of whom are veterans of the global smallpox-eradication effort in which the strategy was introduced and tested. “Kaplan doesn't understand what he's talking about,” fumes Donald A. Henderson, who led the eradication campaign and is now a top adviser to the Bush Administration.

    Now you see it …

    Ring vaccination seemed to have a dramatic effect in a graph published in 1971 and 1975 (top)—but not in Edward Kaplan's new analysis (bottom).


    The aim of ring vaccination is to stamp out an epidemic by isolating smallpox victims and then rapidly immunizing everyone they've come in contact with. In the January issue of Epidemiology, Kaplan and his colleague Lawrence Wein pick apart a widely cited graph, published in scientific papers in 1971 and 1975, that demonstrates the success of this approach. The duo claims that close analysis of the underlying data, gathered in West and Central Africa, reveals that ring vaccination didn't help much at all.

    William Foege, the first author on both of the earlier papers and now a consultant to the Bill and Melinda Gates Foundation, stands by the figure. Henderson, a co-author on the 1975 paper, does concede that “I've always had difficulty with that graph myself,” asserting that it was deliberately drawn to make ring vaccination look good and win support for the strategy. But even though Henderson grants Kaplan that much, he, like Foege, accuses Kaplan of ignoring an abundance of evidence that ring vaccination does indeed work. Jeffrey Koplan, a former director of the Centers for Disease Control and Prevention (CDC) who is now at Emory University in Atlanta, agrees. Kaplan's paper is “very simplistic,” he says, calling it “Epidemiology Lite.”

    So far, the debate about how to handle a smallpox attack has been overshadowed by the issue of preemptive vaccination, which the Bush Administration resolved for now with last month's decision to vaccinate up to 11 million people (Science, 20 December 2002, p. 2312). The postattack game plan is still evolving, but the current version, published on CDC's Web site, calls for ring vaccination at the first sign of an outbreak. But CDC has also asked states to file plans on how they would vaccinate their entire populations within 10 days, if necessary. (The government has not specified just how “bad” an outbreak would have to be for this strategy to be implemented.)

    Last June, Kaplan's team published a computer model in the Proceedings of the National Academy of Sciences showing that, under most scenarios, mass immunization would quell a smallpox outbreak much faster, and with fewer deaths, than ring vaccination would. Henderson and others dismiss Kaplan's model as exaggerating the speed at which the disease would spread. Moreover, mass vaccination alone would never have eradicated the disease globally, they assert. Indeed, the disputed figure, which a CDC official presented at several key policy meetings last year, seems to show that the number of new cases dropped steeply only after ring vaccination was introduced in 20 countries in West and Central Africa in September 1968.

    But Kaplan says the figure uses tricks to make its case. By inappropriately using a logarithmic scale on the Y axis, he says, the authors portrayed gains in overall vaccination coverage (expressed as a decreasing percentage of unvaccinated people) between January 1968 and March 1969 as unremarkable. In fact, says Kaplan, the vaccination rate tripled during that time. The same log scale also exaggerates the plunge in smallpox incidence, he says. So does the fact that the graph presents the ratio of reported to “expected” cases based on the years before 1968—a time when vaccination coverage was much lower.

    When Kaplan reanalyzed the data and plotted the actual number of cases and the percentage of unvaccinated people over time on an arithmetic scale, the two measurements appeared to decline in lockstep; nothing notable happened shortly after ring vaccination began. Success was due to continuing mass vaccination, he concludes, and ring vaccination made a marginal contribution at best.

    Foege strongly disputes that claim, arguing that logarithmic plots are perfectly acceptable in epidemiological graphs. But more important, he says, by March 1969, no more than 60% of the population in West and Central Africa had been immunized—which, under normal conditions, would never suffice to wipe out smallpox. Even in India, where coverage reached more than 90%, he says, the scourge kept festering in some areas. Once ring vaccination was introduced, it was gone within a year.

    Henderson adds that even if the figure is misleading, it served a worthy political goal: persuading reluctant governments in developing countries to adopt ring vaccination. “We used pretty much anything we could lay our hands on” to convince them, Henderson recalls.

    Henderson says he doesn't want to debate the issue with Kaplan any longer. But Kaplan says he's now crunching the numbers from the eradication battle in India, and they seem to support his point of view. And, he adds, there are others in the Bush Administration who are interested in his results.


    Surveys Spot Ring Around the Milky Way

    1. Robert Irion

    SEATTLE—Two teams of astronomers rang in the new year by announcing that our galaxy—like Saturn and a certain hobbit—possesses a grand ring of its own. The thick torus of stars, about twice as far from the center of the galaxy as our sun, probably arose after the Milky Way shredded a much smaller neighbor billions of years ago. “This is a vivid smoking gun of the disruption of a satellite galaxy,” says astronomer Bruce Margon of the Space Telescope Science Institute in Baltimore, Maryland.

    Galactic jewel.

    New surveys have unveiled a thick ring of hundreds of millions of stars around the outskirts of our Milky Way. The structure is about 120,000 light-years wide.


    The new ring, described here on 6 January at a meeting of the American Astronomical Society, is a galaxy-spanning structure consisting of hundreds of millions of stars. It had remained hidden because it lies in the plane of the Milky Way's disk, which contains our sun and most of the galaxy's stars, gas, and dust. Two sensitive surveys of broad patches of the sky have now peered through that clutter to expose a procession of stars beyond the disk, embracing the galaxy in a circle about 120,000 light-years wide.

    Astronomers had seen much smaller arcs and ribbons of stars coursing through our galaxy's vast outer halo, a sparsely populated sphere of old stars. Researchers think these stellar streams are the remnants of dwarf galaxies and globular clusters that dissolved in the Milky Way's powerful gravitational field (Science, 3 January, p. 62). By using a 3.5-meter telescope at the Sloan Digital Sky Survey's (SDSS's) Apache Point Observatory in Sunspot, New Mexico, astronomers have now identified a band of stars wrapping one-sixth of the way around the galaxy.

    The smooth distribution of the stars suggests that a satellite galaxy merged with the Milky Way as long ago as 10 billion years, giving the stars ample time to spread out. Independently, European and Australian astronomers using the 2.5-meter Isaac Newton Telescope at La Palma, Canary Islands, spotted the torus in two other directions, strengthening the suspicion that it girdles the galaxy.

    Astronomers have floated other ideas about how the ring arose. Its near-perfect alignment with the Milky Way's disk suggests that the stars in the ring might have spread out from the galaxy itself, says astronomer Annette Ferguson of the University of Groningen, the Netherlands, a member of the Canary Islands team. But SDSS astronomer Heidi Newberg of Rensselaer Polytechnic Institute in Troy, New York, notes that stars in the ring move through space at similar speeds—whereas stars puffed up from the disk would have more-scattered velocities. “We have to assume that this is a group of stars coherently moving together” and with a common birthplace, Newberg says.


    Tropical Pacific a Key to Deglaciation

    1. Richard A. Kerr

    Despite their obvious role as the solar-driven “firebox” that fuels global weather, the tropics have long been neglected by researchers sorting through the ups and downs of climate over the millennia (Science, 27 April 2001, p. 660). But now paleoclimatologists are bringing the heat-laden tropics back into the climate system.

    In this week's Nature, paleoceanographers present the latest and most persuasive evidence yet that the tropical Pacific did not stand idly by as the world melted out of its latest ice age 18,000 years ago. Instead, the tropical Pacific was a participant, if not the dominant driver, in one of the biggest climate shifts of the past half-billion years. “It is a sea change in how we look at climate change,” says paleoceanographer David Lea of the University of California, Santa Barbara. “It points to the tropics being a big player.”

    Giving the tropics their due required all the latest paleoceanographic tricks. Paleoceanographers Katherine Visser of the U.S. Geological Survey in Woods Hole, Massachusetts; Robert Thunell of the University of South Carolina, Columbia; and Lowell Stott of the University of Southern California in Los Angeles went to a climate record likely to hold vital information on any role for the tropics—a sediment core punched from the sea floor in the Makassar Strait of Indonesia. The piston core comes from the hottest part of the tropical firebox, called the Indo-Pacific warm pool. A near-record 55 meters long, it contained a detailed, well-preserved record locked in microscopic skeletons of a surface-dwelling foraminifer.

    Tropics first.

    Warming of the tropical Pacific (rising green line) preceded and presumably caused ice melting (purple).


    The group members made two kinds of analyses so they could separate the fingerprints left by the melting of the great northern ice sheets from those of the Pacific warming. They measured oxygen isotopic composition, which reflects both varying seawater temperature and seawater salinity. The scientists also determined the ratio of magnesium to calcium in the foram skeletons, a new technique for measuring paleotemperature without salinity's influence. Before the magnesium-calcium technique came along a couple of years ago, paleoceanographers had trouble telling whether tropical warming came first and thus could have driven high-latitude melting. But because the fresh water from the melting ice sheets reduces seawater's salinity globally, the dual measures allowed them to track the start of the western Pacific warming relative to ice melting.

    Visser and her colleagues were able to show that the tropical Pacific was both powerful enough and early-acting enough to drive climate change. The warm pool warmed a hefty 3.5°C to 4.0°C at the end of each of the last two glaciations, according to their analysis, not the 1°C to 2°C assumed since the landmark 1976 CLIMAP study. And the Pacific warming began 2000 to 3000 years before melting ever got under way. “That's a very, very important result,” says Lea, who in 2000 reported a similar lead of tropical warming over ice melting. Adds Thunell, “It's now obvious to most people that the tropics are important.”

    Determining exactly how important the tropics were in triggering deglaciation—or in lesser climate swings from decade to decade or millennium to millennium—will require more work. “We have a system in which it is not just one hot spot controlling everything,” says Thunell. Other players may include the greenhouse gas carbon dioxide, the deep circulation of the North Atlantic, and, ultimately, changes in where and when the strongest sunlight falls as Earth's orbit changes.

    But some meteorologists think that the tropical Pacific might go it alone. In new climate-model simulations by Keith Rodgers of the Laboratory of Dynamical Oceanography and Climatology in Paris and his colleagues, a uniform warming of the glacial tropics by 3°C warms North America's great ice sheet by up to 6°C in summer. In the model, the tropics reach out to high glacial latitudes over a “bridge” of changing atmospheric circulation, much as El Niño does year to year. If researchers can find evidence to support such behavior in the distant past, the tropics will truly have arrived.


    UC Ties at Stake in Los Alamos Shakeup

    1. David Malakoff

    Can this marriage be saved? Top officials of the troubled Los Alamos National Laboratory in New Mexico stepped down this week amid a fraud scandal, stoking rumors that the Department of Energy (DOE) may end the lab's 60-year relationship with the University of California (UC).

    Implosion ahead?

    DOE Secretary Spencer Abraham is reviewing the University of California's management of Los Alamos National Laboratory.


    Lab chief John Browne announced last week that he and top deputy Joseph Salgado were resigning after deciding that “only a change in leadership” could “restore [the government's] confidence” in managers of the lab, who oversee a $2.2 billion budget and nearly 11,000 employees. Browne, a physicist who's spent 23 years at Los Alamos, has been embroiled in several controversies since becoming director of the science and nuclear weapons research center in 1997. In 1999, the lab came under fire for the government's bungled effort to prosecute physicist Wen Ho Lee for mishandling weapons secrets. In 2000, it suffered a temporary loss of classified information, as well as extensive damage from an accidental forest fire. The latest incident involves the November firings of two internal investigators who had revealed credit-card misuse by employees and the apparent loss of computers and other lab equipment worth millions of dollars.

    After each episode, prominent members of Congress and other critics demanded that DOE remove the university as manager of Los Alamos. (UC also runs the Lawrence Livermore and Lawrence Berkeley laboratories in California.) Their criticism builds upon those of some faculty members who have long insisted that the university's stewardship of the weapons labs clashes with academic values. But DOE has repeatedly resisted such efforts to end its UC ties, most recently by extending the arrangement through 2005.

    But the streak could be drawing to a close. The recent problems “have called into question the [university's] ability to run” Los Alamos, DOE Secretary Spencer Abraham wrote in a 24 December letter to UC president Richard Atkinson. Abraham has asked aides to report to him by 30 April on the department's options.

    “This could be the beginning of a very messy divorce,” says one congressional aide familiar with the issues. But finding another manager willing to take on Los Alamos could be difficult, he and other observers say. The University of Texas has expressed interest in running a weapons lab, but any move could generate opposition from those who say no academic institution is capable of imposing the necessary security requirements. Other possible candidates include companies with defense interests and Battelle Memorial Institute, a Columbus, Ohio-based nonprofit that already manages four of DOE's nonweapons labs.

    In the meantime, the 60-year-old Browne says he plans to return to research. The university has named George Nanos, a lab official and retired Navy admiral, to be interim director.


    Relativity Goes Where Einstein Sneered to Tread

    1. Charles Seife

    In physics, quantum mechanics and Einsteinian relativity are usually incompatible. A recent paper, however, has spun them together in an unexpected way.

    In the 30 December 2002 issue of Physical Review Letters, two physicists show that quantum entanglement, a notion that Einstein loathed, can be deeply affected by the laws of relativity. In fact, when particles are sped up to near the speed of light, entanglement can appear seemingly out of nowhere. “Most people in the community think that entanglement is absolute,” says Valerio Scarani, a physicist at the University of Geneva. But he hopes that the new result will change their minds.

    The laws of quantum mechanics state that two particles can be rigged so that their fates are interlinked, no matter how far apart the particles get. Even from halfway across the universe, an entangled particle will instantly “feel” what happens to its distant partner. Einstein despised the idea, because he thought such “spooky action at a distance” violated relativity's basic tenet that information can't travel faster than light. Even now, after decades of experiments showing that entanglement is real, traces of the schism remain. Few researchers have probed what happens when entangled particles travel at relativistic speeds.


    Undaunted, Robert Gingrich and Chris Adami of the Jet Propulsion Laboratory in Pasadena, California, ventured into no-physicist's land. In a thought experiment, they analyzed the behavior of two particles whose spin—a quantum property that is something like the spinning of a top—was entangled when at rest. Then, mentally boosting the particles to speeds close to the speed of light, the physicists calculated the degree to which the two particles stayed entangled. Surprisingly, they found, experimental measurements would indicate that the entanglement had disappeared. Similar calculations showed that particles whose spins were unentangled when viewed at rest could become entangled when boosted to relativistic speeds. “It's quite surprising and not very intuitive,” says Gingrich.

    Actually, Gingrich and Adami say, entanglement isn't really appearing or disappearing; it's just being reshuffled. According to the theory of relativity, just as the length of an object or the timing of an event will vary depending on the motion of an observer, so does a particle's apparent spin. What's more, at high speeds, a particle's spin bleeds into another of its quantum properties—its momentum.

    The team's calculations show that when particles are kicked up to relativistic speeds and lose their spin entanglement, their momenta become entangled to compensate. Similarly, a boosted pair of particles can't acquire spin entanglement out of nowhere. Their momenta must be entangled before the boost, and the momentum entanglement becomes spin entanglement at high speeds. So when both spin and momentum are taken into account, entanglement is neither created nor destroyed by a relativistic boost.

    Gingrich and Adami say their discovery might have implications for ultraprecise clocks. Future Global Positioning System satellites, for example, may keep time by relying on extremely sensitive measurements involving entangled particles. As the satellites hurtle around Earth, disagreements about entanglement might put them out of synch with earthbound observers. “For quantum clock synchronization and long-range communication between satellites, you need to take into account relativity,” says Gingrich.

    Although it might be years before physicists are able to test the team's conclusions with an experiment, Gingrich believes that the work highlights the mysteries surrounding entanglement. “I hope it gives the message that it's an interesting area to study,” he says. “We don't quite understand it.”


    Clinical Recruitment Stumbles on a Logo

    1. Jocelyn Kaiser,
    2. Jon Cohen

    A push by the Department of Health and Human Services (HHS) to approve all publications centrally has got clinical researchers hopping mad at one HHS agency, the National Institutes of Health (NIH). Since last fall, according to government scientists, NIH has canceled patient recruitment ads, costing an extra $81,000 and triggering a significant drop in calls from people interested in volunteering.

    Before and after.

    Offending ads, and a replacement for one, with an added HHS blurb (on bottom).

    HHS has long had a policy that requires prior clearance of all print publications —from clinical trial announcements to brochures to meeting reports. But in past administrations, some NIH institutes were allowed exemptions for ads recruiting study subjects, says John Burklow, acting communications director of NIH. The new enforcement is “a more rigorous implementation of an existing policy,” Burklow says.

    In addition, HHS is requiring that all publications—from ads to business cards—bear the department's name or logo. In October, NIH director Elias Zerhouni announced the requirement. Now all NIH offices are being asked to submit patient ads for approval. “It's not for content but for appearance,” says HHS spokesperson Bill Pierce, to make sure the rules are followed.

    Some institute officials say the tightened rules have caused few problems and that ads have been approved fairly quickly. But other clinical researchers, who asked to not be identified, said the rules have been a nightmare. In October, they were told by NIH to cancel submitted clinical trial ads and radio spots without the HHS identifier, a staffer says, resulting in a loss of $70,000. A later canceled batch cost at least $11,000. In addition, the staffer says the number of calls from possible volunteers dropped from about 600 to 200 a month.

    In November, HHS officials apparently became frustrated that NIH was not complying with the rules. Tracy Self, HHS deputy assistant secretary for public affairs, complained in a 13 November memo to Burklow about an ad promoting AIDS vaccine research that had been published last May in national newspapers and magazines, supposedly without HHS's blessing. The memo, which HHS provided to Science, says that employees “absolutely may not publish unless and until they have received written clearance.” “Willfully” violating the policy, the memo warned, “could result in adverse action.” Self's words about prepublication traveled far and wide as Burklow distributed an e-mail with the subject, “Clear Message from the Department,” quoting Self's memo.

    It turns out the message from HHS was anything but clear. Several officials and public affairs officers became alarmed that the memo implied that researchers must clear scientific publications, book chapters, and the like, which would have been a significant policy change. But HHS spokesperson Bill Hall says that reaction was based on “a miscommunication about the normal process” of clearance and that the ad's content was not an issue. Pierce says that NIH also overreacted by pulling the recruitment ads: “There's no way we fiscally conservative Republicans would want them to do that,” he says.


    A New Road for Indian Science

    1. Pallava Bagla

    BANGALORE—Indian Prime Minister Atal Bihari Vajpayee has laid out a new road map for science and technology that would double the country's spending on research over 5 years, improve training, and streamline bureaucracy. Speaking last week to 6000 delegates gathered here for the annual meeting of the Indian Science Congress, Vajpayee also proposed “a new funding mechanism for basic research” that observers likened to the U.S. National Science Foundation.

    Advancing science.

    Prime Minister Vajpayee outlines new policy to Indian Science Congress.


    The 28-page report grows out of a 2-year dialogue with the scientific community. Although lacking details, it is a major improvement over piecemeal, outdated statements that officials had been using to guide the country since the shift from a state-run to a market-based economy in the early 1990s. “The new policy is anchored in our abiding belief that for science and technology to grow, it must be green, it must be ethical, and it must have a human face,” says physicist Murli Manohar Joshi, cabinet minister for human resource development, science and technology, and ocean development and a key architect of the plan.

    The prime minister called on Indian scientists to reduce the growing number of advanced university degrees “of indifferent quality” being awarded and to avoid “becoming afflicted with the [bureaucratic] culture of our government agencies.” He also urged industry to increase its support for research. N. R. Narayana Murthy, chair of Infosys Technologies Ltd. in Bangalore, a giant global software company, applauded the new policy as a way “to help the Indian S&T community better focus its research efforts.”

    Not everyone is so optimistic, however. C. N. R. Rao, an organic chemist and honorary president of the Jawaharlal Nehru Center for Advanced Scientific Research in Bangalore, says that real change will require considerably more than a few supportive words from the prime minister. Although Rao praises the document's linkage of science and technology and welcomes any boost in spending, he fears that the country's notorious bureaucracy will resist any permanent reform effort.


    The New Face of Traditional Chinese Medicine

    1. Dennis Normile*
    1. With reporting by Ding Yimin in Beijing.

    Asian governments hope that high-volume screening and rigorous clinical trials will unlock the secrets of ancient herbal remedies—and that the results will pass muster with Western scientists

    TOKYO—Epidemiologists had long suspected that the low cancer rates in southeast China might be related to coix, a grasslike relative of maize that is a dietary staple in the region and a key ingredient of many traditional Chinese herbal medicines. But no one had as much faith in coix as pharmacologist Li Dapeng, who in 1975 began trying to coax the anticancer compounds out of the plant's seed. Twenty years later, Li won government approval to market the fruits of his research, a drug he calls Kanglaite, to help cancer patients fight their disease and reduce the side effects from other treatments.

    Although scientists still don't know how it works, the injected drug has been taken by more than 200,000 patients and is China's best-selling cancer treatment. This year, the U.S. Food and Drug Administration approved a phase II trial to test its efficacy in treating non-small-cell lung cancer. It's the first drug derived from a traditional Chinese herbal remedy to go into clinical trials in the United States, and officials and scientists in mainland China, Hong Kong, and Taiwan are betting it won't be the last. All three regions are ramping up efforts to screen the 10,000 or so plants described in the Chinese herbal medicine literature. In addition to searching for new drug leads, they are investigating the herbal remedies themselves.

    Rooting around for drugs.

    Shanghai's Li Dapeng found the active compound for his cancer-fighting Kanglaite drug in a traditional medicinal herb.


    Traditional Chinese medicine (TCM) has also made it onto the region's political agenda. Hong Kong Chief Executive Tung Chee Hwa has laid out a 10-year plan for making the city an “international center for Chinese medicine,” and his government is currently funding 18 TCM research projects that include clinical trials, developing quality standards, and basic pharmacological studies. The Hong Kong Jockey Club Charities Trust is equipping research labs and donating $64 million to get research started at a new Institute of Chinese Medicine. Last year, Taiwanese President Chen Shui-bian proposed spending as much as $1.5 billion over 5 years to develop Taiwan's Chinese medicinal herb industry, although a detailed spending plan is still pending and will need legislative approval. China's Ministry of Science and Technology has made the modernization of TCM one of 12 focal points in its current Five-Year Plan, with $3.6 million budgeted for screening both conventional chemical compounds and medicinal herbs for drug leads.

    Officials see these efforts as a way to use rising research budgets to boost domestic biotechnology research efforts and capitalize on a cultural treasure. “Screening [herbal remedies] is a way for China to try to catch up with Western countries in developing new drugs,” says chemist Yang Xiuwei, director of the National Research Lab of Natural and Biomimetic Drugs at Beijing University of Medical Sciences.

    The timing is right, says biochemist S. D. Kung, who is coordinating herbal medicine research at Hong Kong University of Science and Technology (HKUST). A new generation of Western-trained scientists is eager to take on the challenge of “demonstrating the efficacy [of traditional remedies] to [meet] the standards of the U.S. Food and Drug Administration,” he says. Chinese researchers and officials also want to stay ahead of the growing Western interest in herbal medicine. “This is our culture!” says Yang Ning Sun, director of the Institute of Agrobiotechnology at Academia Sinica in Taipei. “We should be interested in making good use of it.”


    Ironically, as interest in herbal remedies and acupuncture has boomed in the West, the Asian public is turning increasingly to modern medicine. According to a 1999 survey by the Hong Kong government, only 22% of outpatient medical consultations in the city were provided by Chinese medicine practitioners. Officials think the percentage in mainland China is even lower, and they believe that safety concerns are driving people away from TCM. To address that problem, Hong Kong is drawing up regulations to ensure the quality of herbal medicines and the qualifications of practitioners. “Once the regulatory system is in place and we upgrade professional standards, I'm sure the usage rate [for TCM] will increase,” says microbiologist Edmund Lee, who heads the new Hong Kong Jockey Club Institute of Chinese Medicine.

    How well the efforts will pay off—and how soon—is a matter of debate. Even optimists concede that it could take a decade before the work results in marketable pharmaceuticals. Many Western scientists remain skeptical, however, and some believe that the efforts are misguided. Relying on the traditional Chinese medicinal texts for hints to effective remedies for specific diseases, or even direction on what plants to screen, is wishful thinking, says Wallace Sampson, professor emeritus of clinical medicine at Stanford University and editor of The Scientific Review of Complementary Medicine. “Those empirical observations on herbs are unreliable, fanciful, false, [and] irrelevant,” he says, adding that any promising leads would arise purely by chance.

    A few successes

    The belief in the promise of herbal remedies rests on an admittedly minimal track record. The first compound derived from Chinese herbal remedies to enter the Western pharmacopoeia was ephedrine, an amphetamine-like stimulant. A Japanese scientist isolated it in the 1880s from the Chinese medicinal herb mahuang (Ephedra sinica), which was used to treat congestion. It's a common ingredient in over-the-counter decongestants and prescription medications for bronchial asthma, among other products. (Mahuang is also used alone or in combination with other herbal compounds in nonprescription dieting aids, and as a legal way to get high, often under the label “herbal ecstasy.” But a lengthening list of adverse effects has led several countries to ban nonprescription uses, and the United States may soon join them.)


    The next significant pharmaceutical derived from a Chinese medicinal herb didn't appear until a century later, but it may be a far more important find. In the 1970s, Chinese scientists isolated a compound called artemisinin from qinghao, or Artemisia annua, a relative of the sweet wormwood found in North America. The traditional texts identified qinghao as beneficial for fever; the researchers found that artemisinin killed even chloroquine-resistant strains of Plasmodium, the parasite that causes malaria. Recent work in U.S. and European labs suggests that artemisinin may also have anticancer properties. But although artemisinin may be a boon to humankind, the original Chinese researchers earned nothing but bragging rights for their efforts. Zhou Weishan, a chemist at the Shanghai Institute of Organic Chemistry who led the efforts to synthesize artemisinin, says they never patented any part of the work.

    Chinese researchers vow not to repeat that mistake when developing the next drug. When Li decided to take Kanglaite global, “our very capable patent attorneys soon got a process patent and a use patent on the Kanglaite Injection,” says John Harmer, chief executive officer of Salt Lake City-based Kanglaite USA, a subsidiary of Li's Zhejiang Kanglaite Pharmaceutical Co.

    The phase II trial will pair Kanglaite with another chemotherapy to treat non-small-cell lung cancer, following on Chinese results suggesting that Kanglaite enhances the efficacy of chemotherapy and mitigates side effects such as fatigue, nausea, and hair loss. Not as far along in the drug pipeline is a compound derived from huangchi, or yellow root (Astragalus membranaceus), that, like Kanglaite, ameliorates the side effects of cancer chemotherapy. Taiwanese biochemist T. S. Jiang started screening fractions of yellow root more than a decade ago, after observing its traditional use in patients supposedly suffering what could be translated as a deficiency of vital energy, or “qi.” To Jiang, that sounded exactly like the lethargy and weight loss that often accompany chemotherapy.


    The compound, called Xue Bao PG2, has been approved for use in China as a chemotherapy adjuvant treatment and will soon enter phase III clinical trials in Taiwan. Jiang, president of Taipei-based PhytoHealth Corp., created to commercialize the drug, hopes to find a partner to help him penetrate the U.S. and European markets. He says the company is also investigating a drug derived from an herb that is applied traditionally to ease arthritis-like symptoms.

    Full speed ahead

    Scientists in the three regions hope that modern screening efforts will turn this trickle of drugs into a flood. The most ambitious program is at HKUST's Biotechnology Research Institute (BRI), which in 1999 set up a $1.6 million High-Throughput Drug Screening Center for Traditional Chinese Medicine, with support from the government, the Hong Kong Jockey Club Charities Trust, and other local charities and private companies. The center is taking aim at neurological diseases, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and diabetic neuropathy. Catherine Wong, BRI's research projects coordinator, says neurological disorders were chosen because “no good cure is available for most neurorelated diseases yet, and [HKUST] had assembled a critical mass of [neuroscience] experts.”

    The center spent 3 years setting up equipment and developing its own assays before beginning to screen crude herbal extracts, active fractions, and pure compounds for bioactivity. The plants being screened were picked “mainly based on the clinical experience as recorded in the voluminous Chinese medicine literature,” Wong says. She declined to reveal details of what she calls a number of promising hits, adding that they have drawn interest from “major pharma and biotech companies.” Beijing University of Medical Sciences' Yang is similarly circumspect about screening efforts, which he says have already led to at least one patent application.

    It's not surprising that traditional remedies are yielding useful drug leads, Chinese scientists say. But herb enthusiasts think that screening misses the point, because traditional remedies rely on the joint actions of up to 20 herbs. They even worry that screening could produce negative results: “Extracting only some of the ingredients from the herbs might impair the original effectiveness and cause more serious side effects,” says Bian Baolin, director of research and development at the Institute of Herbal Medicine, China Academy of Traditional Chinese Medicine, in Beijing.

    Traditional herbal remedies still suffer a credibility gap in the West because the claims made for them rest largely on anecdotes and clinical observations instead of randomized, double-blind, placebo-controlled trials. Edzard Ernst, a professor of alternative medicine at the University of Exeter, U.K., and colleagues at the Chinese University of Hong Kong (CUHK) reviewed more than 2000 clinical trials reported in mainland Chinese journals and found them almost universally flawed. “What were called randomized clinical trials really weren't, because they didn't have control groups,” says Ernst. “We were very disappointed.” The track record for Western trials is not much better, says Tony Mok, a clinical oncologist at CUHK. Although hundreds of trials have been conducted in the United States and Europe in recent years, he says, “only one or two have been worthy of publication in high-quality, peer-reviewed journals.”

    Ramping up.

    Hong Kong University's High-Throughput Drug Screening Center churns through thousands of compounds every week seeking the bioactive components of medicinal herbs.


    Mok and more than a dozen colleagues at CUHK hope to fill in some of the missing data. They are conducting 20 randomized, double-blind, placebo-controlled clinical trials of traditional herbal remedies and acupuncture, with another dozen in the planning stage. The trials focus on ailments often treated with herbal remedies: asthma, insomnia, drug dependence, Alzheimer's disease, and osteoporosis, among others. “These trials are being led by orthodox clinicians and researchers,” says Mok, who trained abroad, like most of the principal investigators, earning his M.D. from the University of Alberta, Canada, and working in clinical oncology at the Princess Margaret Hospital in Toronto. “The traditional practitioners don't have the training to conduct modern clinical trials,” he says.

    To ensure consistency, most of the trials are using generic herbal formulations. But Mok's trials—one using herbal remedies to counter the side effects of cancer chemotherapy and one pairing herbs and chemotherapy to treat lung cancer—give more scope to traditional methods. All patients are seen not only by an oncologist but also by a traditional practitioner, who prescribes an individualized herbal recipe. Then, depending on a code known only to a pharmacist, the patient gets either the actual remedy or a placebo. Each patient's response is graded on standard measures used in FDA-approved cancer trials, which Mok hopes “will maintain a high standard of quality so we can publish in mainstream scientific journals.”

    A higher bar

    Academic researchers are not the only ones testing the efficacy of traditional remedies. Sometime next year, Taipei-based Cathay Biotech Co. expects to launch FDA-approved, phase II clinical trials of an extract drawn from a collection of 15 herbs as a treatment for hepatitis B. Winston Town, Cathay's chief operating officer, says the multiherb extract is the result of 10 years of work, primarily in China. Starting with a remedy identified in the Chinese medical literature as useful for viral infections, Cathay scientists varied the ingredients, testing different combinations on human subjects until they arrived at a standard formulation. Their extract, given orally as a capsule or injected, has been used clinically in China since 1996. FDA trials will be randomized, double blind, and placebo controlled.

    Cathay's strategy sidesteps two problems that have hindered wider clinical use of herbal remedies: trouble with patents and quality control. Because most herbal remedies are not new inventions, they cannot be patented, and companies have little incentive to pay for the clinical trials that might prove efficacy. Town says Cathay created a novel, nonobvious combination of herbs not described in any of the traditional texts and patented it. Four additional patents are pending on the processing technologies. Cathay also might have solved the second big problem: It chemically characterizes both the raw herbs and the finished product to ensure quality and batch-to-batch consistency.

    Quality control remains a big issue, affecting herbs, formulations, and even the practice of TCM itself. TCM supporters say its diminishing popularity in Asia is due more to lax enforcement of standards than to a failure of the remedies themselves. “I think the majority of scientists in Hong Kong believe [TCM] works,” says Ge Lin, a CUHK pharmacologist studying the pharmacology of herbal remedies. “The problems are in the practice.”

    Ge and others say that spotty regulation leads to inconsistent herb quality, unsubstantiated claims for secret formulas, unqualified practitioners, and both deliberate and inadvertent mislabeling and adulteration, sometimes with fatal consequences. “There are a lot of fake [Chinese] medicines out there,” says HKUST's Kung.


    To restore both local and global faith in the traditional herbal approach, Hong Kong is moving to regulate every aspect of the business. Beginning this year, no one can practice Chinese medicine without a license, which requires completing an approved course of study and passing a test. Herbal pharmacists will soon face similar licensing. On the advice of a new Chinese Medicine Council, 31 potentially toxic herbs can now be dispensed only with prescriptions. The council is also studying ways to regulate the quality of raw herbs and formulations. “Hong Kong is spot on in its approach to regulating Chinese medicine,” says Alan Bensoussan, an associate professor of health sciences at the University of Western Sydney, Australia.

    The screening, trials, and regulations should bring much-needed modern scientific rigor to traditional herbal medicine, says the Institute of Chinese Medicine's Lee. That's even more important today, he notes, as the competition to capitalize on herbal remedies heats up not only among the three Chinese regions but among companies and institutions in North America and Europe as well. “Whenever you approach a subject scientifically, you are bound to generate new knowledge, new analytical techniques, and new methods of quality control,” says Lee. The key, he adds, is making sure that the new, herb-based formulations meet the same standards of safety and efficacy as conventional pharmaceuticals.


    Prion Disease Treatment's Early Promise Unravels

    1. Peter Follette*
    1. Peter Follette is a writer in Ville d'Avray, France.

    PARIS—More than 200 researchers met at a Left Bank hotel in December for the first international conference dedicated exclusively to therapeutics for prion diseases. Their reports, however, dampened hopes of an imminent solution.

    The videotapes showed dramatic improvements in patients being treated for Creutzfeldt-Jakob disease (CJD). A man whose eyes had rolled aimlessly behind closed lids now scanned the room and fixed his gaze on the doctor standing beside him. A woman once mute and inactive smiled, laughed, and held out her hand to a researcher.

    Twisted foe.

    Contorted, toxic prion proteins have so far resisted all medical assaults.


    Both patients had been treated with the drug quinacrine, one of a handful of experimental therapeutics for this debilitating disease. But encouraging as they were, the gains seen on tape were short-lived, reported Masashi Nakajima, a neurologist at Fukuoka University in Japan; within weeks of starting treatment, both patients returned to their previous states.

    Jean-Philippe Brandel, a neurologist at the Pitié-Salpêtrière Hospital in Paris, also reported disappointing results. In a nonblinded study of the same drug, researchers detected neither “clinical improvement in the [CJD] patients nor an increase in their length of survival.”

    Despite initial hopes for quinacrine and a few other compounds approved for human use, scientists have been unable to gain the upper hand on CJD, the most common of several rare, fatal neurodegenerative diseases thought to be caused by misshapen proteins called prions. Most CJD cases occur spontaneously in the elderly, although a propensity for CJD can be inherited. But it is the still-unfolding outbreak of a variant of the disease—vCJD, caused by eating infected beef—that has captured public attention and galvanized research.

    Since 1995, vCJD has killed more than 120 people in Europe—and no one knows how many harbor latent vCJD infections from having eaten tainted beef during the height of the “mad cow disease” epidemic in the late 1980s and early 1990s. Experience with kuru, a prion disease that was spread by ritualistic cannibalism among New Guineans until the 1950s, suggests that prion infections can lie dormant for decades. Stanley Prusiner of the University of California, San Francisco (UCSF), who won a Nobel Prize for his work on prions, says that “for the last 41/2 to 5 years, we've seen 20 to 30 cases a year, and no one knows where this is going to go.”

    Most researchers believe that all forms of CJD are caused by the same miscreant proteins. These misfolded prions coerce normal prion proteins to adopt a pathogenic form, which ultimately kills neurons and leaves the brain riddled with holes, like a sponge.

    Quinacrine is one of many compounds capable of stopping the spread of prions in cultured neuroblast cells or in infected lab animals. It stood out as a drug candidate because it was immediately ready for testing in CJD patients. Used in people for more than 60 years, largely as an antimalarial agent for soldiers serving in the Pacific during World War II, quinacrine was known to cross the blood-brain barrier.

    In 2001, headlines around the world heralded the apparent recovery of Rachel Forber, a young British woman with vCJD who had flown to San Francisco to receive the drug. But, like the Japanese patients in the videos shown at the meeting, Forber's recovery was transient, and she succumbed to the disease a few months later.

    No one knows why quinacrine shows modest, early success in some patients but fails to halt the disease. Testing conditions have been less than ideal. High doses of quinacrine can damage the liver, a side effect that has forced several CJD patients to stop taking the drug. And in the absence of a blood test for CJD, a diagnosis is possible only once symptoms appear, when the damage to the brain is already extensive, perhaps beyond repair. “The problem with all the quinacrine studies right now,” says Prusiner, “is that we are treating only people … with very advanced disease.”

    Reports at the meeting failed to offer much hope that disappointing quinacrine results would be offset anytime soon by success with any of the other drugs that show antiprion activity and have been approved for human use. A clinical trial in Germany suggests that the analgesic flupirtine can slow down the cognitive deterioration seen in CJD patients, but it has no significant effect on the length of survival. And despite some encouraging results in experimental animals with pentosan polysulfate, an anticoagulant that the British High Court ruled last month could be administered to two teenagers with vCJD, this compound cannot pass the blood-brain barrier and must therefore be injected directly into the brain.

    With first-generation drugs falling short, researchers are racing to identify new compounds. Prusiner and his UCSF colleagues plan to screen thousands of quinacrine analogs over the next several years for more potent derivatives. Others are trying to parlay the current explosion of knowledge about prion biology into new treatments. The approaches on display at the meeting included methods to prevent the conversion of the normal prion protein into its misshapen form, ways to nudge the immune system into fighting prions (an approach once thought impossible because of people's natural tolerance to the normal prion protein), and strategies to interrupt the life cycle of prions in cells.

    In one such study, Corinne Lasmézas, a researcher with the French Atomic Energy Commission in Fontenay-aux-Roses, and her colleague Stefan Weiss of the Gene Center in Munich targeted a receptor that interacts with the normal prion protein while it's on the cell surface and that may be involved in its conversion to the misshapen form. When the researchers blocked the receptor's expression in infected cells, there was a striking reduction in the number of malformed prions.

    Although most of the therapeutic strategies described at the meeting aim to rein in the infectious prion particles, some researchers are seeking ways to repair the structural damage to the brain that causes the disease's symptoms. In one presentation, Janet Fraser of the Institute for Animal Health in Edinburgh, U.K., reported that stem- or fetal-cell transplants can colonize damaged areas of the brain and restore some lost tissue in experimental animals.

    Intercepting the disease well before it eats away at the brain, however, would open up the most treatment options. Many people at the meeting emphasized the dire need for diagnostic tools that would permit widespread screening for carriers of the infectious agent. Such tools would signal who should receive compounds—perhaps including quinacrine—that might prevent prions from spreading within the brain, or even from reaching the central nervous system in the first place.


    The Practical Benefits of General Intelligence

    1. Constance Holden

    NASHVILLE, TENNESSEE—About 60 psychologists, cognitive scientists, and psychometricians gathered here last month for the society's third annual meeting.

    Many applied psychologists still regard the intelligence quotient (IQ) test as their field's crowning achievement. But the test has been taking a public battering for the past few decades; it's often denigrated as measuring little more than test-taking ability. Various efforts have been made to supplant the test with better measures of creativity, practical abilities, or street smarts. But at the meeting, the assembled researchers defended IQ. No instrument has yet been devised, they argue, that can outdo classic IQ tests in predicting school and job performance.

    The basis of the predictive power of IQ tests, psychometricians posit, is that they measure “g”—for “general intelligence factor”—an ability to manipulate information that underlies skills such as learning and problem solving. Although the tests come clothed in words and concepts that require cultural learning, psychometricians argue that they in fact measure something deeper. For example, researchers point to the fact that IQ scores correlate with performance on nonverbal (and thus, theoretically, less culturally loaded) tests such as Raven's Progressive Matrices, which involves discriminating among geometric figures.

    But how important is g? That's long been a matter of debate among psychologists, some of whom argue that it's relevant only to academic skills and not to many real-world activities, whereas others say that it is directly relevant to life outside of work or school.

    Sociologist Linda Gottfredson of the University of Delaware, Newark, presented two papers arguing that g is a useful predictor of how well an individual copes in most areas of life. “IQ scores predict a wider range of important social outcomes than perhaps any other psychological trait; … bright people have a tail wind in virtually all aspects of life,” says Gottfredson. Because the g abilities—including learning, reasoning, and problem solving—are relevant in every sphere, she says, life can be viewed as “one long mental-test battery.”

    Health care is a prime example, Gottfredson says. According to a test of health literacy, more than 40% of the population in one study could not, for example, understand directions about taking medicine on an empty stomach, and 60% could not understand a basic consent form. People at this level of comprehension “experience much higher health costs, poorer health, and more frequent hospitalization,” Gottfredson reported. The reason, she claims, is low g, as measured by the health-literacy test. The test retains its predictive power even after controlling for education and social class, she says.

    People who score poorly on IQ tests also have more accidents, Gottfredson points out (see table). Remarkably, she says, “the only accidental death not correlated with lower g is death in a private plane.”

    View this table:

    Health-care providers should give low scorers more support, says Gottfredson, adding that “patients are loath to let people know they don't understand or can't read.” To deal more effectively with all patients, she says, “we might develop simple psychometric measures to help service providers unobtrusively assess people's capabilities for self-care.” There are many areas, from drug labeling to health insurance, where unnecessary complexity could be reduced, according to Gottfredson. Such measures could help service providers adjust their help in accord with clients' “cognitive complexity,” or g.

    The message that g has direct bearing on quality of life was supported by reports from two other researchers. Jody Hendrix, a graduate student at the University of Texas, Austin, used data from the 1998 National Longitudinal Study of Youth to look at the well-being of 466 children from homes deemed high risk (that is, poor and fatherless). Some children, she found, were “resilient,” which she defined as showing no signs of depression, delinquency, or school failure. In her study, the 160 most resilient children tended to have the highest IQs at age 8 or 9, and the low-IQ children were among the least resilient.

    Resilience also seems to be linked to IQ at the other end of life, reported Ian Deary of the University of Edinburgh, U.K. He has been studying a group of 80-year-olds for whom he has childhood IQ records. The high scorers, he found, are the most successful in terms of health, longevity, and daily functioning. High g, sums up Gottfredson, is the ability to “simply live a less error-plagued existence.”

    Physiology of IQ

    High-IQ people use less brain energy than do low-scoring peers when performing a mental task, according to a report 12 years ago by positron emission tomography (PET)-scan imager Richard Haier of the University of California, Irvine. He later found that people expend less brain energy on a computer game after they've learned it—a phenomenon that was more pronounced in those who score well on IQ tests. Now, he's found that high- and low-IQ people also differ when they're doing something that requires little mental effort: watching videos.

    Busy brains.

    Unlike low scorers on a spatial test, high scorers show a correlation between activity in a visual area (cross-hairs) and activity in the frontal lobe.


    Twenty-two volunteers were divided into two groups based on how well they performed on the Raven's geometric shape test. Each was scanned by PET twice—while watching an emotional video and a boring video. Each person's test score was matched with patterns of brain activation during the videos. In the high-IQ group, Haier found a correlation between an area in the back of the brain involved in processing vision and language and an attention area in the frontal lobe, but he did not see the correlation in the low-IQ group.

    Haier says the findings, in press in Intelligence, suggest that the higher scorers are involved in more “active processing” of the material. “We believe this is evidence that smart brains work differently, even when there is no reasoning task,” he concludes.

    John Gabrieli of Stanford University, who does imaging studies of cognitive processes, says Haier's result is “entirely reasonable,” in view of what's known from human and animal brain studies. Gabrieli explains that there's good evidence that the frontal cortex, the seat of the brain's more complex functions, has a big role in choosing what brain regions are activated in the posterior cortex. Therefore, he suggests, it's possible that “people who are better at quick, flexible thinking” show more “tight orchestration” between the two parts of the brain.


    Shrugging Off Doubters, NIH Launches a New Institute

    1. Jocelyn Kaiser

    As the imaging and bioengineering institute builds its portfolio, some researchers worry that their projects could get lost in the shuffle

    It's never easy being the new kid on the block, as the new National Institute for Biomedical Imaging and Bioengineering (NIBIB) is discovering. Congress created this latest addition to the National Institutes of Health (NIH) 2 years ago, despite arguments that it would balkanize research on NIH's campus in Bethesda, Maryland. Now it is ready to join the club: It got a permanent director last fall, and its first advisory board is meeting next week. But NIBIB is still struggling to win over critics, define its priorities, and reassure jittery scientists that their grants won't fall in the cracks between institutes.

    Sharper image.

    Bioengineering projects such as this one, using a patch of needles thinner than a human hair to deliver drugs, will be in NIBIB's portfolio.


    NIBIB's mission is to do technology-based research not specific to an organ or disease. To launch it with a respectable budget, lawmakers last year instructed NIH to transfer extramural grants from other institutes. However, some don't fit NIBIB's mission, according to officials at some NIH institutes, who worry that the resulting problems might take years to correct.

    NIBIB's leaders brush aside such concerns. Deputy director Donna Dean says it's painful for program managers at other institutes to release grants, but no worthy projects will go unfunded. She notes that NIBIB has already expanded the field, supporting new research in areas from biosensors to small-animal imaging that wouldn't fit comfortably in NIH's other institutes. Its budget could more than double this year, to $283 million, if Congress approves a proposal that passed the Senate. NIBIB's new director, Roderic Pettigrew, a radiologist from Emory University in Atlanta, says NIBIB's goal is straightforward: “optimizing the positive impact that technology can have on the nation's health-care agenda.” But doing that without stepping on the toes of other institutes presents a challenge.

    Other new institutes were established in recent years by expanding a piece of an existing institute or by promoting a center. NIBIB came into being from scratch on 29 December 2000 when President Clinton signed a law mandating its creation. Lawmakers were responding to years of lobbying by radiologists who teamed up with a bioengineering advocacy group to argue that technology got short shrift at NIH.

    To give NIBIB a portfolio in 2001, NIH's 26 other institutes and centers picked out $67 million in grants that they agreed belonged at the new institute. But NIBIB's congressional sponsors weren't satisfied. Congress ordered a working group to identify more.

    This group, which included three NIH staffers and six outside scientists, started last winter with a list of 2647 extramural grants culled by key word from NIH's grants database. The panel winnowed the tally to 889, supposedly by eliminating those specific to a disease or organ. This “very tentative list,” says Dean, was converted to dollar figures in a report delivered to Congress in May by then-NIH deputy director Ruth Kirschstein. Six institutes were told to transfer $10 million to $60 million in grants each, for a final total of $150 million. “They have tried to make [this process] sound pseudoscientific, but it's really a political game,” says one NIH program manager.

    Reaching out.

    NIBIB chief Pettigrew seeks collaborations.

    The initial list included illogical transfers, staffers say, such as a tumor vaccine study that happened to have “molecular engineering” in the title. Institutes were given limited bargaining room to swap for other grants or give cash instead, program managers say.

    Although the negotiations have ended, NIH has not made public the final list because the NIH 2003 budget is pending in Congress. The funding transfers to NIBIB are a “mishmash” that includes many disease- or organ-specific grants, NIH staffers say, as well as 25 of 42 technology centers funded by the National Center for Research Resources (NCRR). “The list [of centers] has no logic that I could discern,” says Watt Webb of Cornell University, who is unhappy that his biophysics imaging center is being moved from NCRR to NIBIB.

    NIH program managers say they have short- and long-term concerns about the reshuffling. Some see an immediate risk that grants could get caught in a bureaucratic loop if they are steered to NIBIB and get turned back for failing to match NIBIB's still-evolving goals. Such projects might become orphans. One official, for example, says his institute has “taken a pass” on several new applications in areas NIBIB is supposed to fund. Researchers, meanwhile, are confused about whether to word their grant proposals so they will be routed by reviewers to NIBIB or to other institutes. If all the grants go to NIBIB, “people are worried that [it] won't have enough money,” says bioengineer Bernhard Palsson of the University of California, San Diego (UCSD). Over the long term, some program officials worry that NIBIB's staff won't have enough disease-specific expertise to steer technology into clinical applications.

    NIBIB officials say these fears are not well founded. NIH will “feel a responsibility” to make sure grants that receive good scores in review are funded; this is how the system works, Dean says. And to gain additional expertise in disease areas, NIBIB expects to issue joint program announcements with other institutes. Pettigrew, who came on board in September after the grant transfers had been decided, says, “We will be very collaborative.” Outside scientists who lobbied for NIBIB also believe the disruptions are temporary. “I don't think people need to worry,” says bioengineer Shu Chien of UCSD. “The institute is developing quite well.”

    Dean also points out that changes to NIH's review system should hearten the bioengineering and imaging community. For example, the instructions to grant reviewers have been revised to make it “more explicit” that grants can be judged by engineering principles rather than a disease-related hypothesis, she says. The NIH Center for Scientific Review, which reviews most NIH grant submissions including all of NIBIB's, has proposed adding more bioengineers and imaging experts to panels as part of an ongoing overhaul of study sections. NIBIB will eventually have some of its own study sections.

    Hot field.

    Optical imaging—here, using fluorescent probes to give a view of rat lymphocytes—will be in the portfolio of NIH's new institute.


    As for NIBIB's intramural component, Pettigrew says, NIH officials are discussing it; decisions could still be years away. Dean says that members of Congress who expressed interest last year in placing NIBIB's intramural arm in Mississippi have apparently dropped the idea (Science, 5 April 2002, p. 24).

    To focus its agenda, NIBIB organized a workshop last month in Bethesda aimed at defining priorities for the next 5 years. The 40 or so participants, including outside scientists, agreed on a list topped by new imaging technologies, biosensors, optical imaging, biological systems, and cell/molecular imaging. Pettigrew says the meeting “confirmed that the institute is on track.” Its conclusions will be presented to the NIBIB council on 16 to 17 January.

    Pettigrew says NIBIB's emphasis on technologies rather than specific diseases is “a natural for me.” An M.D. with a doctorate in applied radiation physics from the Massachusetts Institute of Technology, in his own work he's using high-field magnetic resonance imaging to study arterial wall changes that can lead to plaque development and stroke, heart attack, or kidney infarction. He expects to continue this research part-time in a lab on the NIH campus, saying: “If you're going to lead cutting-edge research, it's good to do cutting-edge research.”

    Despite the uncertainty about NIBIB's agenda, some grant managers at NIH predict that the institute will have a positive impact on bioengineering and imaging research. William Heetderks of the National Institute of Neurological Disorders and Stroke points to an NIH bioengineering consortium started in 1997, which “led to a flowering and explosion” of research. If NIBIB can do the same, he says, it will be a success.


    Cool Corals Become Hot Topic

    1. David Malakoff

    New discoveries about deep-water corals have mobilized marine scientists to strengthen international collaboration and mitigate damage from fishing

    When Robert Stone tells people he studies corals in Alaska, he gets some puzzled looks. “Everybody knows corals live in warm waters,” says Stone, a marine ecologist at the National Oceanic and Atmospheric Administration's (NOAA's) Auke Bay Laboratory near Juneau. “They think I'm joking.”

    He's not. While many scientists focus on understanding warm, shallow tropical reefs, a growing number of them are turning their attention to little-known “cool corals.” Researchers are using a new generation of submersibles and other technologies to probe the cold, dark waters of the deep ocean where these corals live. To their surprise, they have found remarkably vibrant coral gardens in the inky blackness and enormous deep-water reefs whose size confounds conventional scientific wisdom.

    Next week, cool-coral experts from Europe, the United States, and Canada will gather in Ireland to begin crafting an international research plan to document the distribution, biology, and ecology of these unusual organisms. Along the way, they also hope to strengthen efforts to protect deep-water corals from fishing practices that threaten to reduce some ancient reefs to rubble.

    Researchers agree that mystery enshrouds their subjects. “We know that these corals can be very old and very fragile,” says Anthony Grehan, one of the meeting organizers and an ecologist at the National University of Ireland's marine institute in Galway. “But we have a lot to learn.”

    To the untrained eye, cool corals look much like their tropical kin. They range in size, shape, and color from ivory cups no bigger than a thimble to crimson gorgonian fans 3 meters tall. Some build rock-solid edifices, whereas others are soft or leathery. But there are important differences. Deep-water corals can survive much colder temperatures —for instance, down to 4 degrees Celsius. And in living at sunless depths of up to 2000 meters, the corals lack the symbiotic algae called zooxanthellae that convert sunlight into energy for tropical corals.

    Coral fan.

    Researcher Robert Stone holds a find from Alaska.


    Researchers believe that some cool corals sift their food from passing currents or periodic “snowfalls” of dead plankton. But scientists know relatively little about how these corals evolved, reproduce, recover from damage, or interact with other sea-floor creatures. And climate scientists wonder if old corals can help them unravel ancient ocean conditions, much as tree rings provide clues to past weather. Scientists do know that deep-water corals grow very slowly—sometimes less than a centimeter per year.

    In part because deep-water corals are hard to study, researchers showed little interest in early accounts of prodigious colonies of cool-water coral, including reports in the 1980s of extensive gardens along the U.S. and European coasts. A decade later, however, they took notice after Norwegian scientists announced the discovery of an enormous reef in 250 meters of water along the Sula Ridge, about 100 kilometers offshore. The 14-kilometer-long structure, composed mostly of hard, bristly Lophelia coral, rises up to 30 meters off the sea floor. Some of the corals appeared to be hundreds of years old, the researchers noted in papers published in the late 1990s, and the reef might date back several thousand years.

    At about the same time, a French-led European team discovered vibrant coral gardens of Lophelia and other species growing 600 meters down atop huge, unusual sea-floor mounds off the coast of Ireland. “Even the most hard-bitten [researchers] were absolutely stunned,” says Grehan. “It was totally unexpected at those depths.”

    Soon, researchers from Scotland to New Zealand were combing old data for hints of similar structures and launching expeditions with new, remotely operated submersibles to videotape previously inaccessible areas. They also had access to state-of-the-art multibeam sonar maps of the ocean floor that highlight humps, ridges, and sediment types that might be hospitable to corals. By the end of last year, such tools enabled the Norwegians to document an even bigger Lophelia reef (35 kilometers long), and British researchers found smaller growths atop mounds off Scotland. Canadian marine scientists discovered an exotic coral landscape on a 100-square-kilometer swath of sea floor off Nova Scotia. U.S. researchers hunted down their own treasures, including hauntingly beautiful colonies along Alaska's Aleutian Islands that Stone began documenting last summer.

    Increased knowledge also led to growing concerns about the impact of destructive fishing practices in deep waters, particularly bottom-hugging trawling nets. The Norwegians discovered that huge swaths of their Lophelia reefs had already been crushed by the nets, and they have barred trawling in several unspoiled areas. Canada created a coral preserve in 2001, and Ireland, the United States, and other nations are formulating similar plans.

    But picking the right places for these reserves is a challenge, notes marine ecologist Les Watling of the University of Maine's marine center in Walpole. “We're still pretty shaky on basic distribution and abundance patterns,” he says.

    Participants at the Ireland workshop—sponsored by NOAA and the Irish government's marine institute—hope to fill those and other gaps by laying the groundwork for collaborative studies around the Atlantic. Both the United States and Europe have already poured more than $5 million into cruises and studies, and agencies on both sides of the Atlantic have requested proposals for future work. The network may eventually spread to the deep-water corals in the Pacific.

    An international conference this fall in Erlangen, Germany, is expected to produce solid plans for at least one major international coral cruise in 2004. Stone, meanwhile, would be satisfied if these meetings simply raise awareness that corals aren't confined to the tropics. “I'd have a lot less explaining to do,” he says.

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