News this Week

Science  08 Jun 2001:
Vol. 292, Issue 5523, pp. 1592

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    New Rules on Foreign Contacts Resurrect Cold War-Era Distrust

    1. Vladimir Pokrovsky,
    2. Elena Kokurina*
    1. Vladimir Pokrovsky and Elena Kokurina are writers in Moscow.

    MOSCOW—Is it a benign measure to protect Russian scientists from unwittingly revealing state secrets, or a chilling return to Soviet-style authoritarianism? Debate is swirling over a sweeping directive from the Russian Academy of Sciences (RAS) that requires its 55,000 researchers to report any international activities and contacts to the academy's governing presidium.

    The directive, stamped “for internal use only,” has an eye-catching title: “The Academy of Sciences' action plan to avoid any harm to the Russian state in the sphere of economic and scientific cooperation.” It orders “specialist departments” and institute chiefs to analyze “international agreements signed by scientific bodies in order to prevent the transmission abroad of information concerning national security.” It also calls for “strengthening controls on articles being prepared and the exchange of information with foreign countries” in order “not to permit the publication abroad of unauthorized information.”

    News of the directive was first divulged on Echo Moskvy radio by prominent human rights campaigner Sergey Kovalyov. He reported that the directive requires researchers at the 357 RAS institutes to file reports on all international grant applications, articles sent for publication abroad, travel to international conferences, and the activities of foreign colleagues who visit Russian labs. Kovalyov charged that the directive is yet another sign of Russia's transformation into a “police state.” The Kremlin moved quickly to dismiss that allegation. Deputy Prime Minister Valentina Matviyenko, quoted by the ITAR-TASS news agency, called the charge “groundless.”

    It's hard to know whom to believe. It is unclear how institutes will implement the directive, how the presidium plans to use the information, or in what instances foreign activities will be reported to the KGB's successor agency, the Federal Security Service (FSB). The undefined scope of the FSB's involvement worries researchers, who are already more prudent in the wake of several high-profile cases in which the FSB relied on an ambiguous reading of what constitutes a state secret to level accusations against Russian researchers and an American technology specialist (Science, 10 March 2000, p. 1729, and 15 December 2000, p. 2043).

    Back to the future.

    Critics charge that the academy's futuristic building may house Soviet-era thinking.


    Physicist Mikhail Feugelman of the prestigious Landau Institute of Theoretical Physics in Moscow takes a dark view. He charged last week on Echo Moskvy that the directive may be a thinly veiled attempt to allow the FSB to exert more control over the scientific community, such as by barring publication of certain articles in foreign journals or by preventing certain researchers from traveling abroad or seeking Western grants. If these fears prove true for scientists not involved in classified research, he said, a research establishment already crippled by a massive brain drain in the early 1990s could suffer further losses. “I'll stop persuading my students to stay in Russia,” he said.

    Other prominent researchers see merit in the new rules and discount a return of Soviet-style controls. “The old system of secrecy with all its drawbacks and idiotic features is ruined today,” says Leonid Bezrukov, deputy head of the RAS Institute for Nuclear Research in Moscow. But that may result in secrets being leaked inadvertently, he says, and in that respect, the directive “is very useful, as a scientist cannot always understand what is secret and what is not.” Clearing submissions to foreign journals, he adds, could offer protection if the FSB chose to investigate someone's activities. He notes that scientists have left themselves particularly vulnerable by Internet postings; these, too, must be cleared under the new rules.

    Resolving the intent of the directive is challenging, in part, because the presidium has not revealed where the order originated. Several RAS institute heads contacted by Science speculate that the FSB is the source. Others trace the initiative to the presidium, which is increasingly asserting its authority over the institutes in the run-up to elections this autumn that will usher in a new RAS president for the first time in 10 years. RAS scientific secretary Nikolai Plate responds that the directive's aim is solely to remind scientists to guard intellectual property. “There are no attempts to restrict the freedom of Russian scientists to contact scientists from other countries,” he says.

    Most scientists are warily watching how institutes interpret the directive, which is supposed to be implemented this month, and how aggressively it's enforced. “It might be a completely harmless document,” Alexandr Berlin, director of the RAS Institute of Chemical Physics in Moscow, says hopefully. Then again, he notes, “it might be something much more serious.”


    Academies Seek Release of Egyptian Scientist

    1. Constance Holden

    Leaders of the U.S. science academies are protesting an Egyptian court's decision to jail Saad Eddin Ibrahim, a longtime human rights activist and perhaps the most prominent social scientist in the Arab world. Ibrahim was convicted in Cairo on 21 May of misusing foreign funds and defaming the Egyptian government, drawing a prison sentence of 7 years. The presidents of the U.S. National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine sent a plea for mercy to Egyptian President Muhammed Hosni Mubarak on 31 May, saying that Ibrahim did not get a fair trial. They ask Mubarak to make a “magnanimous gesture” by “immediately and unconditionally” releasing him.

    Human rights groups and scientists around the world have been stunned by the court's action, which also led to jail sentences for 27 of Ibrahim's colleagues at the Ibn Khaldoun Center for Development Studies in Cairo. This has been “absolutely a body blow to human rights activity in Egypt,” says Morton Panish, formerly of AT&T Bell Labs and a member of the academies' Committee on Human Rights. The Ibn Khaldoun center, which Ibrahim founded 12 years ago, has been shut down.

    The trial took place in Egypt's Supreme Security Court, a special court operating under “emergency” laws enacted in the 1970s to deal with Islamic extremists. Observers say the charges against Ibrahim appeared flimsy: For example, he was accused of mishandling a $250,000 grant from the European Union for monitoring election procedures, even though the donor had found no misuse of funds. According to the academy committee's report on the affair,* released last week, the prosecutor called no witnesses, and the judges returned a guilty verdict without reviewing volumes of defense material—just 90 minutes after the arguments had been completed. The Egyptian Embassy in Washington, D.C., however, defended the verdict in a letter to The Washington Post, saying that the trial was open, proper procedures were followed, and Ibrahim has the right to appeal.


    Ibrahim looks out from cage where he was put for the trial.


    The Committee on Human Rights has been following Ibrahim's case closely and in February dispatched representatives including Panish to attend part of the trial. Their report calls the treatment of Ibrahim “symptomatic of an increasingly less tolerant attitude toward those working to promote democracy and the growth of civil society.” Says Panish: “Many Egyptians thought this would come out OK. Now they are in shock.”

    Some believe that Ibrahim's efforts to expose official misconduct got him in trouble. Although he has worked for the United Nations and the Egyptian government, the committee's report points out that since the mid-1990s, the Ibn Khaldoun Center has increasingly turned its attention to the government's sluggishness in introducing democratic reforms. Ibrahim has also been involved in studying touchy areas such as conflict between Copts and Muslims. Last summer, while out on bail, Ibrahim said in a speech at the American University in Cairo that he believed his uncovering of election fraud in parliamentary elections in 1995 and his plans to keep tabs on the fall 2000 elections prompted his arrest. Observers say Mubarak may have been ruffled by an article in which Ibrahim sniped at Arab leaders, including Mubarak himself, for grooming their sons to be their successors. “I think the government has been irritated with him for a while,” says Torsten Wiesel of Rockefeller University in New York City, chair of the human rights committee.

    The Egyptian press has been hostile to Ibrahim—who is married to a U.S. citizen, sociologist Barbara Ibrahim, and has dual citizenship—characterizing him as a chronic troublemaker backed by anti-Egyptian supporters of Israel. Wiesel says the committee is working to counter the bad press by contacting about 50 science academies internationally. “We are asking them to write so there are more voices,” he says.

    Ibrahim and his family have steadfastly claimed to have faith in Egypt's system of justice. They now plan to appeal to Egypt's highest judicial authority, the Court of Cassation. That appeal may be heard in a few months.


    German Leaders Spar Over Bioethics

    1. Robert Koenig,
    2. Gretchen Vogel

    BERN—An intense debate over the ethics of embryo and genetic research is setting Germany's president against its chancellor, splitting traditional party allies, and stepping up the pressure on a new federal bioethics council that was scheduled to hold its first meeting on 8 June.

    The dispute had been simmering for months, but it was energized by guidelines issued in May by Germany's main research funding agency, the Deutsche Forschungsgemeinschaft (DFG), that would open the door for researchers to import embryonic stem (ES) cells (Science, 11 May, p. 1037). The federal research ministry asked the DFG to postpone a decision on the first German proposal to use ES cells—submitted by Bonn University neuropathologist Oliver Brüstle—until political leaders and the new bioethics council had explored ethical concerns over such research.

    The council is stepping into a war zone. On 18 May, German President Johannes Rau—whose office is largely ceremonial, but whose opinions carry considerable weight—asserted in a major speech that “certain possibilities and plans of biotechnology and genetic engineering run contrary to fundamental values of human life.” Concerned about research on ES cells and on preimplantation diagnosis—the testing of test tube-fertilized embryos for genetic defects before they are implanted into the mother—Rau demanded a strict demarcation of the ethical limits of research. “Questions about life and death affect us all. We therefore must not leave them to the experts,” he said. “We must debate these issues and then decide on them together.” He also conjured Nazi ghosts, warning that “no one should forget what happened in the academic and research fields” in Germany during World War II. “An uncontrolled scientific community did research for the sake of its scientific aims, without any moral scruples,” Rau said.

    In response, German Chancellor Gerhard Schröder—like Rau, a Social Democrat—led a freewheeling debate in the Bundestag (the lower house of Parliament) on 31 May by defending researchers seeking new treatments against diseases such as Alzheimer's and Parkinson's. “The ethics of healing and of helping deserve just as much respect as the ethics of creation,” said Schröder, who does not want to ban limited stem cell research. He warned that German leaders must keep in mind the potential consequences of “the neglect of research and development” if rules are so strict as to deprive people with intractable diseases of possible treatments. Schröder said it was wrong for politicians to accuse ES cell researchers “of having dark and unethical motives.”

    But Schröder found limited support for his view in the Bundestag. Several fellow Social Democrats lined up against his position, and the leader of the opposition Christian Democrats, Angela Merkel, argued that even importing ES cells for research “violates the spirit,” if not the letter, of Germany's Embryo Protection Law. Merkel plans to introduce legislation that would place a moratorium on such research until Parliament comes to a decision. Delegates of the Green Party—part of Schröder's coalition—also opposed both ES cell and preimplantation diagnosis research. “I've never seen any scientific topic in Germany as vividly debated,” says Detlev Ganten, director of the Max Delbrück Center for Molecular Medicine in Berlin and a member of the bioethics panel, comprised of 24 scientists, theologians, legal experts, business executives, and philosophers. “I find it healthy.”

    Others question whether the panel has any chance of mending the political schism. The ethics council is bound to struggle with the issue of ES cell research, says panel member Christiane Nüsslein- Volhard, a director of the Max Planck Institute for Developmental Biology in Tübingen. “It's likely that such research will be done mainly in England and Israel, and not in Germany and the United States,” predicts the Nobelist, who says she finds Rau's approach “too extreme” and generally agrees with Schröder's pragmatic attitude. Brüstle, who was in Israel last week discussing the possibility of importing ES cell lines for his research project, says he does not expect Germany to agree on a new policy on ES cell and preimplantation diagnosis research anytime soon, in part because of next year's federal elections.


    Canada Eyes Front-Row Seat in Mars Program

    1. Andrew Lawler

    BOSTON—Canada's space efforts over the past 2 decades have focused largely on radar satellites and a robotic arm for the international space station. Now Canadian space officials are asking scientists to help them plan a Mars mission so outstanding that it can overcome tight budgets and leapfrog other research priorities to win government funding.

    As a first step in that campaign, some 120 researchers met late last month in Montreal to kick around ideas ranging from drilling beneath the martian surface to returning samples from one of its moons. “We look at this as the next major space program for Canada,” says Marc Garneau, recently named executive vice president of the Canadian Space Agency. “We want to be involved with Mars in more than peripheral ways.”

    Garneau thinks the timing is right to pump new funds into space science, which receives about 15% of the agency's $234 million annual budget. Spending is winding down on the $600 million robotic arm, which was installed on the space station this spring but is suffering from technical troubles. But even so, the estimated cost of a Mars mission—likely to top $300 million even with the help of international partners—would require a bigger overall budget, says Garneau, who is hoping for an increase in the fiscal year that begins 1 April 2002.

    The agency intends in the months ahead to develop a set of possible missions for 2007 or 2009 that draw on Canadian technological and scientific expertise, complement existing international efforts, and appeal to the public's sense of adventure. This summer the space agency will prime the pump by funding a series of separate space science projects at Canadian universities focusing on planetary geology, atmospheres, terrestrial analogs, and astrobiology.

    Canada already has one instrument headed to Mars. It's a thermal plasma analyzer from the University of Calgary, designed to gather data on the origin and composition of the martian atmosphere, that is due to arrive in late 2003 on board the Japanese Nozomi spacecraft. Other technologies now in use around Earth, such as Canada's highly successful synthetic aperture radar, could provide detailed maps of Mars from a high- flying orbiter. And the nation's experience with robotics could be used on a sophisticated rover on the martian surface. The space agency and Canadian industry already are working on a prototype small arm for a lander. In addition, researchers from the Arctic research station on Axel Heiberg Island hope to apply to Mars their expertise in searching for life in extreme environments.

    One promising technology is a special drill, adapted to the planet's dry conditions, that could penetrate as deep as 10 meters. Hojatollah Vali, a biomineralogist at McGill University in Montreal who helped organize the May workshop, says that a group of geologists and astrobiologists at the meeting suggested putting such a drill on a martian lander. Another workshop group has proposed an orbiter with instruments to study the martian atmosphere, and a third team recommended a sample return from Phobos or Deimos. Neither moon has been explored, notes Alan Hildebrand, a geologist at the University of Calgary who participated in the workshop.

    Canadian officials hope to integrate their plans with efforts already under way by NASA, the European Space Agency, and the Japanese National Space Development Agency. “We want to fill a void and not duplicate,” says Alain Berinstain, chief scientist for the Canadian Space Agency's space exploration program. “We'd be delighted and overjoyed to have major Canadian participation,” says James Garvin, chief scientist for NASA's Mars planning. He says the U.S. agency already is planning its own 2007 lander but might welcome a subsurface drill or robotic arm for that mission or a synthetic aperture radar on a 2009 martian orbiter.

    Time is short and funding uncertain. But Canadian space and planetary scientists are hoping that their blue-sky thinking won't be too late to secure a visit to the Red Planet.


    Faster Maps Mean Fewer Mice

    1. R. John Davenport

    A computer may be worth 1000 mice if a new genetic mapping technique pays off. The approach could markedly speed the first step in identifying genes associated with diseases, making the process cheaper and more efficient.

    Although some human diseases are triggered by a genetic change in a single gene, most involve multiple genes that confer susceptibility to the disease. Because the genetic diversity of human populations makes finding these genes difficult, scientists have turned to the laboratory mouse. One way to home in on these disease-related genes is to look for naturally occurring genetic variation among inbred strains of mice that have different traits—for instance, body weight or cholesterol level. By looking for genetic markers that are associated with particular values of the trait (for instance, high body weight or high cholesterol levels), researchers can identify regions on the chromosomes, called quantitative trait loci (QTL), that likely contain genes that contribute to the trait.

    But finding these QTLs is costly. Geneticists must cross two mouse strains that differ in the trait, produce hundreds or thousands of offspring, and determine the phenotype and genetic signature of each mouse. It takes months just to produce the mice and often years to analyze the animals. And that's just the starting point, as finding a QTL provides only a rough idea of where the gene resides. Further work is needed to pinpoint the gene and the mutations within that gene that lead to increased susceptibility to a disease.

    Now, a team of scientists has come up with a way to accelerate that process. As they report on page 1915, they have compiled a database of common genetic markers called single nucleotide polymorphisms (SNPs) and developed a computer algorithm to sift through these “alternative spellings” among mouse strains. This enables them to identify QTLs “in silico” in a fraction of the time it currently takes researchers in the lab.

    “Identifying a QTL isn't going to take years anymore; it's going to take weeks at greatly reduced cost,” says Robert Karp, director of the genetics program at the National Institute on Alcohol Abuse and Alcoholism, who was not involved in the work. The technique “makes the first part of [gene identification] easier, which means you're not exhausted for the rest of the search.”

    To pull this off, Gary Peltz of Roche Bioscience in Palo Alto, California, along with colleagues at Roche, Stanford University, and Oregon Health Sciences University in Portland, pooled SNP data on 15 commonly used strains of inbred mice. The Roche team identified more than 500 of the SNPs; the remaining 2848 were identified by other researchers.

    Then Peltz and his co-workers created an algorithm that would let them query the SNP database to identify QTLs almost instantly. A user inputs phenotype data on a particular trait, say, body weight, that varies among multiple strains of mice. The algorithm looks for SNP patterns that are similar among strains with similar phenotypes, but different among strains with different phenotypes. Those SNP patterns indicate QTLs that could contain genes contributing to that trait.

    To test the algorithm, the researchers fed published phenotypic data for 10 different traits (including tendency to consume alcohol, bone mineral density, and an allergen-induced asthmalike response) into the computer and checked the computer-predicted loci against published QTLs mapped through the conventional process of mouse breeding. They matched 75% of the time.

    Although the method still leaves large chunks of DNA to search for the culprit gene, Peltz anticipates that as the database grows, the algorithm will pinpoint smaller candidate regions with higher accuracy. He hopes to have 5000 SNPs by the end of the year and to eventually add several additional strains, which will provide more genetic and behavioral diversity to compare. The team, funded by the National Institutes of Health, has made its SNP database and gene- hunting algorithm freely available on the Web ( “It's a great resource,” says geneticist Carollee Barlow of the Salk Institute for Biological Studies in La Jolla, California.

    The traits used in the trial run haven't been mapped down to the gene level by any method, so no “gold standards” exist to test the method, cautions Dean Shepherd of the University of California, San Francisco: “To prove what the method is really worth, we'll have to actually find some specific mutations that explain the differences in phenotype.” As other researchers search for their own favorite genes, the effectiveness of this new method for mapping QTLs should quickly become apparent. Shepherd, for one, is optimistic, saying “It's extremely likely that in the near future this will really have a significant payoff.”

  6. PCR

    Roche Dealt a Setback on European Taq Patent

    1. Robert F. Service

    A key biotechnology patent belonging to Swiss pharmaceutical giant Hoffmann-La Roche ran aground on the legal shoals of a third continent last week. On 30 May the European Patent Office (EPO) revoked Roche's patent on native Taq polymerase, a crucial element of the polymerase chain reaction (PCR), the ubiquitous technique used to amplify snippets of DNA. Roche officials say they will appeal the ruling. But this is a costly setback, because the company is already fighting to overturn related decisions in both the United States and Australia.

    The ruling marked another in a string of victories for a group of small biotech companies that have challenged Roche's Taq patents in recent years. The companies, led by biological reagent supplier Promega of Madison, Wisconsin, have argued among other things that labs in the United States and Russia isolated the native Taq (n-Taq) enzyme before scientists at Cetus Corp., which transferred the patent to Roche in 1992. The Munich-based EPO agreed, ruling that the patent EP-0-258-017 B1 was invalid. “This decision reaffirms once again what Promega and many others in the research community have long believed: that the Taq patents should never have been issued,” says Promega CEO William Liton.

    The decision means that Promega can continue to sell n-Taq without paying royalties to Roche. Roche officials argue that this has little effect on the bottom line, because n-Taq makes up only 10% of the Taq they sell; the other 90% is recombinant forms of Taq (r-Taq), which are widely used in automated gene-sequencing machines and are covered by separate patents. But Promega's general counsel Brenda Furlow contends that the legal damage to Roche is broader, because some of the provisions of the patent struck down by the EPO applied to r-Taq, and Roche's separate r-Taq patent is currently being challenged in Europe. “We think the recombinant [Taq] claims will fall,” says Furlow.

    Genetics researchers are hoping that Roche's patent troubles will bring down prices. Although gene sequencers predominantly use r-Taq, n-Taq remains widely used in a host of other genetic studies, such as genotyping, a procedure used to sort out how genes are inherited in families. These studies typically require Taq or another polymerase enzyme to amplify specific DNA strands. “This is done very well with native Taq,” says Maynard Olson, who heads a genome sequencing center at the University of Washington, Seattle. But cost remains a big issue.

    Taq currently costs about 50 cents for the amplification step used in a single round of genotyping, says Olson: “There would be a lot more genotyping done if it only cost a penny for the Taq.” Olson adds that he is hopeful that if Roche does wind up losing its hold on the Taq patents, this will encourage other companies to enter the market and bring down the cost. “That would be very welcome for us,” agrees James Weber, a geneticist whose lab conducts approximately 6 million genotypes a year at the Marshfield Medical Research Foundation in Wisconsin. Weber says that about 8% of his research budget currently goes to paying for Taq. “If we could reduce the cost of Taq, we could produce more genotypes per year. No doubt.”


    Returning Alien Rocks Right the Second Time

    1. Richard A. Kerr

    The first time astronauts brought rocks and soil back from the moon, efforts to protect Earth from possible contamination were “a travesty,” says meteoriticist John Wood. Exposures to Apollo lunar material meant that if anything pathogenic had come with them, “we'd have been in bad trouble,” says Wood, of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts. To do it right the next time—when Mars rocks are returned as early as 2014—researchers need to start deciding now how to handle extraterrestrial samples both safely and cleanly, according to a report* released last week by the U.S. National Research Council (NRC).

    The challenge of avoiding infecting Earth with any ET life or dirtying Mars samples with terrestrial materials will require a quarantine facility “unlike any in existence,” says Wood, who chaired the NRC committee. “It's not an insurmountable task, [but] we need to get started.”

    Memories of Apollo's troubles heightened the urgency. At the Lunar Receiving Laboratory (LRL) in Houston, “there was not really enough time to do what needed to be done,” says Wood. When samples arrived in 1969, tight schedules and NASA's stress on astronauts' convenience combined to make contamination happen. The hatch was popped open while the Apollo capsule was still bobbing in the Pacific, and a leak in the receiving lab sent 11 exposed people into quarantine with the astronauts. Others fled the area to avoid guards charged with enforcing quarantine rules, according to the report.

    Although the first Mars sample return won't have astronauts to contend with, it will require a receiving facility more stringent than any now used to contain exotic killers like the Ebola virus. In biological containment facilities, the chamber containing the biological agent is kept below atmospheric pressure so that the inevitable leaks will let outside air in but prevent anything inside from getting out. In a clean room designed to keep samples pristine, the reverse is true. The room is held at a higher pressure to keep chemical contaminants out. But any Mars sample receiving lab must “simultaneously achieve biological containment and clean room conditions in one facility,” says Wood.

    The challenge of keeping anything from getting in or out while examining Mars samples mandates 7 years of planning and construction before the samples arrive, the NRC committee concludes, plus whatever time is first required to sort out the technical problems. That means starting now, the committee says, even if the first samples don't get here until 2014. With the LRL's lapses in mind, the committee also recommends that NASA keep it simple this time around—no chilling the samples to Mars temperatures or keeping them at martian atmospheric pressure. NASA welcomes most of the committee's recommendations, says NASA's planetary protection officer, John Rummel. “I would hate to think we'd make the same mistakes” as Apollo workers, he says, “and this report gives us some good guidelines to avoid them.”


    Director of Natural History Museum Quits

    1. Elizabeth Pennisi

    The director of the world's most visited museum has resigned to protest a planned reorganization that would separate the museum's scientific and educational roles. Robert Fri, who heads the Smithsonian Institution's National Museum of Natural History in Washington, D.C., said in a memo to his staff on 28 May that he cannot commit to the proposed changes. He plans to step down by October.

    About three-quarters of the Smithsonian's 425-member scientific staff are based at the Natural History Museum, including geologists, anthropologists, paleontologists, and systematic biologists, as well as technicians who manage the museum's extensive collections of rocks, plants, animals, and artifacts. Many of these researchers have been up in arms in the 2 months since the new Smithsonian secretary, Lawrence Small, proposed closing some research units and reorganizing scientific activities into several centers of excellence (Science, 13 April, p. 183; 11 May, p. 1034).

    Under the new plan, the role staff scientists would play in the museum's exhibits and other educational activities is unclear. Researchers are now actively involved in the design and content of museum exhibits and public programs, and the public has always “recognized exhibits as the veneer with the research and collections behind them,” says David Dilcher, an evolutionary biologist at the University of Florida, Gainesville, who is on the museum's advisory board. “If you cut the threads that pull these three things together, then what will become of natural history at the Smithsonian?”


    Robert Fri says he can't commit to the Smithsonian's reorganization plan.


    Fri, who led the museum for 5 years, said he could not implement Small's proposed plan: “I do not feel that I can make that commitment enthusiastically,” he wrote in his memo. In a prepared statement, Small paid tribute to Fri's contributions but had no comment about his reasons for resigning. Fri's replacement has not been named.

    Museum staff members were disappointed by Fri's decision. “He has been a good manager. He has brought stability that we had not had at the museum,” says Smithsonian paleontologist Brian Huber. But they weren't surprised. Both Dilcher and advisory board member Emilio F. Moran, an anthropologist at Indiana University, Bloomington, said Small had excluded Fri from the planning process for some time. “Many of us are very concerned about the very top-down, nonconsultative approach of the secretary,” says Moran.

    Small's proposal to shift the museum's research into a separate administrative center, says Dilcher, will leave the museum a “skeleton devoid of the energy of the scientists.” He says he understands why Fri apparently does not want to become the caretaker of these bones.


    Transatlantic War Over BRCA1 Patent

    1. Michael Balter

    PARIS—It was not the usual press release hyping a scientific discovery. Last week, when a French-U.S. team reported a newly identified mutation in BRCA1, a human gene linked to elevated risk for breast and ovarian cancer, the Institut Curie announced the result with a broadside against Myriad Genetics, a Salt Lake City, Utah-based biotech firm. Myriad holds at least 17 patents worldwide on the use of BRCA1 and a related gene, BRCA2, and has developed an automated test for mutations in these genes. But because the test doesn't pick up defects like the newly identified mutation, Curie claimed, it represents “a potential danger” to French cancer patients.

    The attack is the opening volley in a battle over the right of Myriad—which earlier had won a hard-fought battle over its patent position in the United States—to market its test in Europe (Science, 12 December 1997, p. 1874). The Curie and 16 other labs are considering a challenge to a European patent awarded to Myriad last January for BRCA1 and BRCA2 applications. Officials at Myriad—whose researchers played a key role in the discovery of both genes—have vowed to protect their intellectual property.

    Mutations in BRCA1 and BRCA2 are thought to be responsible for up to 10% of all breast cancers. A team led by Curie geneticist Dominique Stoppa-Lyonnet describes the new mutation—a deletion of three exons, or coding regions, in BRCA1—in this month's issue of the Journal of Medical Genetics. They discovered the mutation in a patient at Cedars-Sinai Medical Center in Los Angeles who had been diagnosed with breast and ovarian cancer, as well as in other women in her family. She had previously been tested with Myriad's BRACAnalysis technique, which uses automated sequencing to scan for mutations and deletions. But Myriad's test does not detect large-scale DNA deletions or rearrangements, and it failed to pick up any BRCA1 or BRCA2 mutations in the patient.

    The Curie-led team identified the three-exon deletion (covering 11,600 DNA base pairs) using a technique called combed DNA color bar coding. The technique was developed in 1994 by Aaron Bensimon, a co-author on the Journal of Medical Genetics paper, and his Institut Pasteur colleagues. Pasteur has patented the technique, which consists of stretching out DNA strands on treated glass and visualizing their structure with fluorescent molecular probes. In the paper, the team argues that such large-scale alterations—several of which have been identified over the past 3 years—may account for as much as 36% of all BRCA1 mutations, and that the Pasteur technique should be considered as an alternative or supplement to Myriad's test.

    That's where the Curie's attack on Myriad comes into play. Myriad's European patent, and several it has pending, may make it impossible for European clinicians to use the Pasteur technique for BRCA1 and BRCA2 testing, Stoppa-Lyonnet contends. “Their patent gives them the right to demand a monopoly,” she says. The dispute reflects a broader concern among many European researchers that current interpretations of European patent law allow biotech and drug companies to put a lock on the use of human genes (Science, 23 June 2000, p. 2115).

    Myriad officials counter that the French criticisms are off base. “If there is a technique that can detect a mutation not detected by our test, we are not stopping anyone from getting that test done,” says Greg Critchfield, president of Myriad Genetic Laboratories, a subsidiary that markets BRACAnalysis. However, if Myriad were to develop techniques to detect large deletions and rearrangements, the company would have the exclusive right to use them, Critchfield claims. “What gives [Curie] the right to take over our discovery.” he asks. “A company has to protect its intellectual property rights.”

    France's Genetics and Cancer Group—a network of 17 labs, including the Curie, that conduct BRCA1 and BRCA2 testing using a variety of methods—is discussing a legal challenge to the patent Myriad received in January. This “opposition” procedure must be filed within 9 months of the award of a patent—in this case, no later than October. Stoppa-Lyonnet says that the group will decide whether to file an opposition “in the coming weeks.”


    Mass Extinctions Pinned on Ice Age Hunters

    1. Leigh Dayton*
    1. Leigh Dayton writes from Sydney, Australia.

    Until the late Pleistocene era, 11,000 to 50,000 years ago, big, exotic mammals and flightless birds roamed the planet. Then, suddenly, they were gone. Who killed the Pleistocene megafauna? So far the prime suspect in the prehistoric whodunit, Homo sapiens, has walked free, but incriminating new evidence from Australia and North America is tightening the net. If findings reported in this issue of Science convince the scientific jury, humans will be guilty of two counts of serial mass murder, 35,000 years apart, and rival suspects such as climate change will be off the hook.

    “I think we have this problem nailed,” says John Alroy, an evolutionary biologist at the University of California, Santa Barbara. On page 1893, Alroy describes a detailed computer model of North American ecology during the Pleistocene. The model, which simulates the population dynamics of humans and 41 large herbivores, shows that mass extinctions were “unavoidable” once people showed up, Alroy says.

    Meanwhile, scientists led by geochronologist Richard Roberts of the University of Melbourne and mammalogist Timothy Flannery of the South Australian Museum in Adelaide claim to have settled the long-standing question of when the Antipodean megafauna disappeared. On page 1888, they identify a continent-wide extinction of large mammals and birds around 46,400 years ago—a few thousand years after people are believed to have appeared there.

    “The bulk of the evidence is now clearly aligned with a human explanation for the [Australian] event,” says Gifford Miller, a geochronologist at the University of Colorado, Boulder. Miller also finds Alroy's simulation a “convincing argument” that human beings had a hand in the North American extinctions.

    Whatever caused them, the die-offs, like their victims, were colossal. In Australia, 28 genera and 55 species of vertebrates are estimated to have vanished—including fearsome claw-footed kangaroos that weighed in at 300 kilograms and the whopping 100-kilogram Genyornis, the heaviest bird ever known. Ice Age America boasted huge saber-toothed tigers, woolly bison, giant antelopes, and the woolly mammoth. By around 11,000 years ago, more than two-thirds of America's large mammals had died out.

    Intriguingly, all the extinctions, north and south, occurred after modern people arrived. But proving humans guilty has been a slow and hotly disputed process. Analyses of past climates, computer modeling, and conventional archaeological and paleontological studies have failed to provide conclusive evidence.

    Hoping to finger a culprit, Roberts dated megafauna-bearing sediments from 28 sites across Australia. Because traditional radiocarbon dating is unreliable beyond about 40,000 years in the past, Roberts used optical and thorium-uranium methods to get ages for rocks and sediment associated with large-animal remains. Optical dating relies on the fact that electrons in buried quartz grains become excited over time to higher energies by radioactive elements in the surrounding sediments. By measuring the cumulative exposure, scientists can estimate how long ago exposure to sunlight last reset the quartz clock to zero—and thus when remains were buried. Thorium-uranium dating provides the date of calcite bands on the floors of caves, above and below the animals. This provides a minimum and maximum age of death. Taken together, the dates show that large animals at the sites were buried between 51,200 and 39,800 years ago, just as human beings were spreading across Australia.

    Although the results are not a “smoking gun,” Roberts believes they “definitely” implicate people. “If humans hadn't arrived in Australia, the megafauna would not now be extinct,” he says. He and Miller think the lethal blow was indirect. Aborigines, they believe, changed vegetation by firing the landscape, possibly to make hunting and traveling easier. The result was less food for big browsing animals, and hunting and climate fluctuations may then have tipped them to oblivion.

    In North America, by contrast, hunters may have been in the thick of the faunicidal fray. That's the idea behind the “blitzkrieg” hypothesis that geoscientist Paul Martin of the University of Arizona, Tucson, proposed in 1967. Martin reasoned that early hunter-gatherers followed their prey across the top of Asia to North America, and then south into the heart of the continent. Hungry hunters caused local extinctions, which ultimately drove total populations down the slippery slope to extinction.

    To test Martin's ideas, Alroy programmed a computer to run a large-scale simulation of virtual hunters moving into virgin territory in late Pleistocene North America, starting 14,000 years ago. He included a range of parameters that let him specify how quickly the invaders traveled, how efficiently they hunted, and how various prey species competed with one another for food. Alroy found that no matter how he adjusted the variables, mass extinctions ensued. Even the slowest, clumsiest hunters unleashed ecological devastation. Hardest hit were large animals, whose slow growth rates and long gestation periods made it difficult for them to bounce back once their populations slumped.

    Not everyone is convinced. At the American Museum of Natural History in New York City, biologists Ross MacPhee and Alex Greenwood blast Alroy's model, because they say overkill can't explain why extinctions stopped 10,000 years ago, when the Pleistocene gave way to the modern Holocene era. If hunters were wiping out species tens of thousands of years ago, MacPhee says, “they should be just as bad through the Holocene.” Instead, he and Greenwood suspect that the huge animals succumbed to a “hyperdisease”–a highly contagious, lethal virus introduced by human newcomers. But Alroy counters that MacPhee misses the model's main point: showing that the late Pleistocene extinctions could have occurred even without climate change.

    If the two studies hold up, they carry a contemporary message, Alroy says: “The results show how much havoc our species can cause, without anyone at the time having the slightest idea of what is going on, much less any intention of causing harm.”


    Can Adult Stem Cells Suffice?

    1. Gretchen Vogel

    In the political debate over the use of embryonic stem cells, some opponents claim that malleable adult cells can take the place of their embryonic cousins. Many scientists aren't so sure

    At a U.S. Senate hearing last month, a lobbying group passed out a flyer to reporters and congressional staff members entitled “Current Clinical Use of Adult Stem Cells to Help Human Patients.” On the front it lists a dozen ailments, including autoimmune diseases, anemia, and cancer, all of which have been treated with stem cells derived from bone marrow or other tissues. At the bottom, the flyer reads: “Other side of page: complete list of conditions for which embryonic stem cells are in clinical use to help human patients.” The other side, of course, is blank. The flyer is correct—but misleading. Adult bone marrow cells, at least, have been in use for more than a decade, whereas human embryonic stem (ES) cells were isolated for the first time just 3 years ago.

    The group behind the flyer, called the Coalition of Americans for Research Ethics, believes research using embryos is immoral and unnecessary. To bolster their case, they cite recent papers that demonstrate the often surprising flexibility of stem cells found in a variety of adult tissues, from human fat, placenta, and even dead brains.

    But most scientists in the field—including those who work with adult-derived cells—caution that recent advances, although promising, do not mean that adult cells can replace the need for those derived from embryos or fetal tissue. For some diseases, they say, adult cells may indeed turn out to be the better choice. But for other applications, embryo-derived cells have some distinct advantages. Scientists working mostly with ES cells derived from mice have found that they multiply more readily in the lab than do their adult counterparts, providing as many cells as needed, and they seem far more proficient in producing certain specialized cell types, such as dopamine-producing neurons and insulin-producing cells. “It's incorrect to say that these published papers show that the adult cells are equivalent to embryonic stem cells for treating diabetes and Parkinson's,” says Ron McKay of the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland.

    This scientific dispute over the relative merits of embryonic versus adult stem cells might seem arcane, but it is at the heart of raging political debates in several countries, including Germany (see p. 1811) and the United States. In Washington, the Bush Administration is weighing whether to let the National Institutes of Health go forward with its plan to fund studies of human embryonic and fetal stem cells. Both sides are lobbying hard.

    Fat and Frankenstein

    Both types of cells could prove to be a tremendous boon to medicine. Eventually, scientists would like to use stem cells to replace damaged or worn-out tissues—for instance, to treat paralyzing spinal cord injuries. This might work if scientists can figure out how to guide the growth of stem cells—immature cells that can replicate themselves and give rise to mature daughter cells. The stem cells themselves are found in many tissues in the body and also in developing embryos and fetuses. Those isolated from embryos are pluripotent—meaning that, with the correct cues, they can give rise to any kind of cell in the body. Stem cells in adult tissue are often multipotent—they can produce many, but not all, cell types.

    For many years scientists assumed that development was a one-way street: Once committed, cells lost the ability to turn back. Only embryonic cells, they believed, had the power to develop into any desired cell type. But over the past several years, that assumption has been debunked as dozens of studies have shown that cells from the brain could become blood cells, for example, and vice versa.

    One recent paper captured the public's imagination as few others have. In the April issue of Tissue Engineering, surgeon Marc Hedrick of the University of California, Los Angeles, and his colleagues reported that fat cells isolated after liposuction could become cells resembling cartilage, bone, and muscle. The paper has prompted numerous sound bites, with several politicians volunteering to give up some of their fat to further research. But although the image of liposuction as an altruistic operation might be attractive, developmental biologist Douglas Melton of Harvard University says the study leaves several key questions unanswered. He speculates, for instance, that the team may have cultured a circulating hematopoietic stem cell, rather than a fat cell. That may be so, says co-author Adam Katz of the University of Pittsburgh, but he suspects people will prefer liposuction to bone marrow donation any day.

    Cell biologist Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston is similarly circumspect. He points out that the four cell types the team described—fat, cartilage, muscle, and bone—are all part of the mesenchymal cell family and have already been derived from several stem cell sources. The paper reports no sign that the cells could become nerve cells or the much-sought-after pancreatic cells. Fat cells might be abundant, Spiegelman says, but “they are a far cry from being the answer to everything we need.”

    The next paper to make a major splash described isolating stem cells from cadavers. “Frankenstein cells,” several headlines proclaimed. As described in the 3 May issue of Nature, neuroscientist Fred Gage of the Salk Institute for Biological Studies in La Jolla, California, and his colleagues cultured neural progenitor cells from brain tissue taken from cadavers shortly after death. Gage notes that the team members were careful to call their cells neural “progenitors” instead of neural “stem cells.” The cells could divide and differentiate in culture, but the team didn't show that they could both replicate themselves and produce mature daughter cells—the true test of a bona fide stem cell. The cells also had a limited lifetime in culture—a major disadvantage for scientists trying to coax cells to become a particular tissue type. In short, says Gage, the technique is a long way from clinical application.

    At least two companies have announced—but not published—that they have identified or produced pluripotent cells without using embryos or fetal tissue. Although the claims got plenty of play in the press, most stem cell scientists are dubious. In April, a company called Anthrogenesis, located in Cedar Knolls, New Jersey, announced via a telephone press conference that it had isolated stem cells from human placentas that might be the equivalent of human pluripotent stem cells. These placental cells can differentiate into nerves and blood vessels, the company says, although chief scientific officer Robert Hariri says they are still characterizing the cells. “These claims … were just absolutely absurd,” says John Gearhart of Johns Hopkins University, who isolated pluripotent stem cells from fetal tissue in late 1998. “If you don't have published research reports, how are [colleagues] supposed to judge a claim?” Hariri says the company has submitted several papers describing the cells, although none have been published yet.

    And PPL Therapeutics, based in Edinburgh, U.K., and Blacksburg, Virginia, says that its scientists have generated “pluripotent” cells from bovine skin cells. Company managing director Ron James announced the claim at a meeting in February but said researchers will not present their work in detail until they have secured a patent—a process that could take nearly a year, according to PPL scientist David Ayares.


    Strong signs from bones

    In one tissue, at least, scientists agree that the results are encouraging. In the past few months, a series of papers has strengthened the idea that cells in the bone marrow can respond to cues from damaged tissue and help repair it. Until recently, doctors had only attempted to use bone marrow stem cells to reconstitute the blood or immune system.

    But late last year, two teams reported that mouse cells derived from bone marrow could become neuronlike cells (Science, 1 December 2000, pp. 1775 and 1779). In April, another two groups reported that bone marrow-derived cells could help repair damaged heart muscle. In one study, Piero Anversa of New York Medical College in Valhalla and Donald Orlic of the National Human Genome Research Institute in Bethesda, Maryland, induced heart attack-like damage in 30 mice. They then injected the bone marrow cells into surviving heart tissue. Nine days after the injection, the transplanted cells were forming new heart tissue—muscle cells as well as blood vessels—in 12 of the 30 mice, the team reported in the 5 April issue of Nature.

    In the other study, Silviu Itescu of Columbia University in New York City and his colleagues isolated cells from the bone marrow of human volunteers, then injected the cells into the bloodstream of rats in which the team had induced heart attacks. Signals from the damaged heart evidently attracted the transplanted cells, the team reported in the April issue of Nature Medicine; 2 weeks after the injection, capillaries made of human cells accounted for up to a quarter of the capillaries in the heart. Four months after the operation, rats that received the blood vessel precursors had significantly less scar tissue—and better heart function—than control rats.

    Perhaps most impressive, in the 4 May issue of Cell, scientists reported that a single cell from the bone marrow of an adult mouse can multiply and contribute to the lung tissue, liver, intestine, and skin of experimental mice. Researchers knew that a tiny subset of cells purified from bone marrow had the potential to multiply and give rise to all the blood cell types, but isolating those cells has been very difficult. To increase their chances of capturing the elusive cells, Diane Krause of Yale University School of Medicine and Neil Theise of New York University Medical School and their colleagues performed a double bone marrow transplant. They first injected bone marrow cells from a male mouse, tagged with green fluorescent protein, into the bloodstream of female mice that had received a lethal dose of radiation. Two days later, they killed the recipient mice and isolated a handful of green-tagged cells that had taken up residence in the bone marrow. (Previous studies had suggested that the most primitive transplanted cells lodge in bone marrow.) They then injected irradiated mice with just one of the green-tagged cells accompanied by untagged, female-derived bone marrow cells that survive about a month. When the scientists killed the surviving mice 11 months after the second transplant, they found progeny from the cells in lung, skin, intestine, and liver as well as bone and blood. “Bone marrow stem cells can probably form any cell type,” says Harvard's Melton.

    Even so, Krause says her work highlights the need for more work on ES cells rather than suggesting a replacement: “We basically have a black box. We put the cells in at the beginning and look at the mice” several months later. Because only six of the 30 mice that received a single-cell transplant survived, Krause estimates that one-fifth of cells harvested from the first transplant recipients have such broad potential. The scientists don't know why the most versatile cells go to the bone marrow in the first transplant, nor can they predict which ones might have the potential to multiply and differentiate.

    Melton also notes that cells from bone marrow have one major drawback: Although they are fairly easy to collect from donors, the cells do not grow well outside the body—and not for lack of trying. “Biotech companies have spent tens of millions of dollars on that problem,” Melton says. “I don't think it's going to happen very easily.”

    Elusive islets

    One of the most sought-after commodities is pancreatic islet cells— potentially the key to treating type I diabetes. Researchers are trying both embryonic and adult cells and arguing over which is most likely to pay off. The fragile pancreatic islets respond to changes in blood sugar and produce insulin, one of the key hormones that regulate metabolism. In type I diabetes, the immune system attacks and destroys the cells, leaving patients dependent on frequent injections of insulin and vulnerable to serious side effects. A few teams have reported success in growing insulin-producing cells in the laboratory from precursor cells present in the pancreas of both adult mice and humans. Last year, Ammon Peck and his colleagues at the University of Florida, Gainesville, and Ixion Biotechnology in Alachua, Florida, did so with cells from adult mice. When they transplanted some of these lab-derived cells into three diabetic mice, two survived without insulin injections for 3 months. Last July, Susan Bonner-Weir and her colleagues reported in the Proceedings of the National Academy of Sciences that they had succeeded in growing insulin-producing cells from adult human pancreas cells. But NINDS's McKay cautions that the numbers in both papers are small. “There are interesting cells that you can get out of the adult pancreas. They may indeed generate [useful cells], … but right now, the evidence for that is really very thin.” Peck says he is confident his technique works. He and his colleagues are working to repeat the experiments in dogs and in pigs.

    McKay and his colleagues also recently described a method for turning mouse ES cells into pancreas-like cells that produced insulin in response to glucose, albeit just a fraction of the amount that mature cells produce (Science, 18 May, p. 1389).

    Two are better than one

    Most researchers say they need access to both embryonic and adult stem cells. McKay points out that embryonic cells have one huge advantage over adult-derived cells: their ability to divide in culture. “The ES cell will be the basis for how you will get large numbers of cells,” he says. Gearhart of Johns Hopkins adds that the ability of embryonic and fetal cells to divide in the lab makes them a vital tool for learning how differentiating cells behave. “Answers to the problems of how you would do things with adult stem cells will probably come from the embryonic and fetal cells,” he says. “There's no other way you're going to get that information.”

    But ES cells have plenty of limitations, too. For one, murine ES cells have a disturbing ability to form tumors, and researchers aren't yet sure how to counteract that. And so far reports of pure cell populations derived from either human or mouse ES cells are few and far between—fewer than those from adult cells.

    Even if adult-derived cells do become the favorite for some treatments, such applications are years away, says McKay. The long-term consequences of stem cell therapies are completely unknown, as few animal studies have looked at results longer than a year after transplants. And scientists need to know more about the process of cell differentiation before anyone will be able to tell which cells hold the most hope for curing disease, McKay notes. “All of these cells,” he says, “are partial solutions for the moment.”


    An Embryonic Alternative

    1. Gretchen Vogel

    The rallying cry of those who oppose work with embryonic stem cells is that cells from adults are sufficient (see main text). But if scientists must study embryonic stem cells, they should focus on those from rhesus monkeys. That's the argument of Kevin Fitzgerald, a bioethicist at Loyola University Medical Center outside Chicago. Fitzgerald, a Jesuit priest who holds a Ph.D. in molecular genetics, is a founding member of the Coalition of Americans for Research Ethics, a group that lobbies against the use of human embryonic stem cells. Biologists can't draw a line somewhere after fertilization that marks the start of “human life,” says Fitzgerald. “It's a spectrum all the way along. That's why the end- and beginning-of-life issues are so difficult.” For that reason, he thinks that embryos deserve the same protection and respect as infants and so shouldn't be destroyed to obtain embryonic stem cells.

    To determine the potential of stem cells, Fitzgerald suggests pushing ahead with work on adult stem cells and, for any embryonic studies, using primate cells. “We've skipped the somewhat obvious middle step: primate research,” he says. Such cell lines already exist: Reproductive biologist James Thomson of the University of Wisconsin, Madison, derived embryonic stem cells from rhesus monkeys before he succeeded with human cells. Not only can monkey cells enable scientists to answer most fundamental questions without treading on shaky ethical ground, says Fitzgerald, but preclinical trials will have to be conducted, likely in monkeys, before any human trials begin.

    Thomson agrees that primate studies will be critical before attempting stem cell therapies in humans. But he says that for basic studies it is far more efficient to use human cells. Mouse and human reagents are readily available, but “every time you want to work with the rhesus cells, you really have to reinvent the wheel.” And with data from the human genome project now available, identifying key regulatory genes is much simpler in human cells than monkey cells, he says.

    John Gearhart of Johns Hopkins University in Baltimore, who works with stem cells derived from fetal tissue, also doubts that primate cells will suffice. “One of Alexander Pope's maxims was, ‘The proper study of mankind is man,’” he says. Rhesus cell lines “would be far preferable to mouse [lines]. … Would they be sufficient? I don't have an answer to that.” Research over the past 2 decades has turned up surprising differences in how various mouse stem cell lines behave. If such differences exist in human embryonic and fetal cell lines, scientists need to understand them as well, Gearhart says. So although there is clearly a place for primate cells, Gearhart, for one, will concentrate on human cells.


    National Count Reveals Major Societal Changes

    1. Daniel Walfish*
    1. Daniel Walfish writes from Beijing.

    China's population is becoming older, better educated, and more transient. It is also harder to track, resulting in a big jump in the census undercount

    BEIJING—When China's National Bureau of Statistics declared this spring that it had counted 1.266 billion people in the country's fifth national census, it confirmed China's status as the world's most populous nation. But another number—the estimated 22 million people the census missed—may provide a better indicator of how China has changed. Experts say that the undercount, some 30 times larger than that in the last census a decade ago, reflects the impact of a rising standard of living, growing concern about privacy, and a large but elusive migrant population. In addition, the process of allocating it demonstrates how politics interacts with statistics in China's socialist bureaucracy.

    Demographers say that the overall count rings true, based on predictions of 1.27 or 1.28 billion (Science, 17 November 2000, p. 1288). “It's a little bit lower than our projection, but it's basically accurate,” says Zhai Zhenwu, a demographer at People's University of China in Beijing. Even so, the net undercount of 1.81%, based on postcensus sampling, is a huge jump from the official rates of 0.06% in the 1990 census and 0.015% in 1982. The current number falls within international standards—2% is considered “acceptable,” says Y. C. Yu, former head of demographic and social statistics at the United Nations—and is not far above the 1.6% in the 1990 U.S. census. Still, the number may be squishy. Last month the director of the statistics bureau surprised a group of demographers by telling them that government officials are “increasingly doubting” its accuracy.

    Longer life.

    (Top) China's population is aging, with a smaller share of children and more elderly. Missing Persons. (Bottom) A flood of migrant workers into cities like Beijing contributed to a soaring undercount in the 2000 census.


    The exact size of the undercount isn't the only problem. When the central bureau tried to assign portions of the missing 22 million to subtotals from the different provinces, provincial officials balked. Population figures reflect how well officials have enforced China's strict birth control policies. In addition, a larger population means a lower per capita gross domestic product. Finally, a big undercount means that the province did a poor job with the census. “American states would rather be larger. Chinese provinces would rather their population be smaller,” explains Zhai.

    The result, say demographers who attended a recent lecture by the statistics bureau's director, was a set of negotiations between the central bureau and the provincial officials. Even then, the bureau wound up with 1.05 million people that no one would accept, a group the bureau labeled “awaiting decision.”

    Politics was supposed to be kept out of the fifth census. Central government officials swore that there would be no recriminations for discoveries that could reflect poorly on individuals or local officials—like extra children born in violation of the birth control policy. But the past decade of economic development has transformed Chinese society and loosened the government's control of people's lives. One result is a flow of up to 100 million rural workers into cities. At the same time, the established urban population has become wealthier, freer, and more protective of its privacy.

    Those trends complicated the 2000 census. The 10-day count was extended by weeks in some provinces after census takers had problems tracking down migrants and preliminary totals were unrealistically low. “There was a lot of difficulty this time,” acknowledges Sun Jingxin, the former deputy director of the statistics bureau and an adviser on the 2000 census.

    Demographers won't be able to assess the true quality of the census until next year, when the bureau releases full results. But they are already beginning to draw conclusions about important changes in Chinese society.

    For example, the bureau has revealed that nearly 7% of the population is 65 or older, meeting the U.N. criterion for an “aging population” and the resulting social burdens. That situation will only grow worse, says Tian Xueyuan, a demographer with the Chinese Academy of Social Sciences in Beijing, citing estimates that the percentage will grow to 22% by 2050. Family patterns are changing, too, notes demographer Jiang Leiwen of Beijing University, with the average family size dropping from 3.96 in 1990 to 3.44. Fewer extended families could intensify the plight of the elderly in a society where the young traditionally care for the old.

    The Chinese population also appears better educated. The bureau says that 6.7% of the population over 15 is illiterate, compared with 15.9% in 1990, and that 3.6% were enrolled in or had completed higher education, compared with 1.4% in 1990. Although some of that rise is undoubtedly due to a recent drive to broaden enrollment in higher education, Jiang says that the jump might also reflect the prevalence of fake degrees.

    One eagerly awaited statistic is the sex ratio at birth; recent sample surveys have indicated that male babies might outnumber females by as much as 119 to 100. One number already reported—a rise in the total sex ratio, from 1.066 to 1.067, in favor of males—is cause for alarm, says Jiang, who notes that the number should have shrunk as the population aged, because women live longer than men.

    Chinese demographers are not happy about it, but most would probably agree with Jiang when he says that “politics does affect the accuracy of the census.” For despite its limitations, the census is still the best tool they have for painting a picture of Chinese society.


    Can Organisms Speed Their Own Evolution?

    1. Marina Chicurel*
    1. Marina Chicurel is a writer in Santa Cruz, California.

    Intriguing hints from cell and molecular biologists suggest that they might, but evolutionary biologists are not yet convinced

    In November 1970, Miroslav Radman, a molecular geneticist now at the Université René Descartes in Paris, stunned his colleagues with a heretical proposal: that bacteria harbor a genetic program to make mutations. Through this program, Radman suspected, bacteria can crank up their mutation rates in stressful situations, helping accelerate their own evolution. Virtually no one believed him.

    But 3 decades later, with the discovery of a new family of DNA-synthesizing enzymes, or polymerases, Radman feels vindicated. Unlike regular polymerases, this new family is prone to make mistakes. And recently, two independent groups led by molecular geneticist Susan Rosenberg of Baylor College of Medicine in Houston, Texas, and Patricia Foster of Indiana University, Bloomington, fingered one of them—polymerase IV—as a generator of mutations in times of stress. Says Radman: “These are the polymerases that I was dreaming about 30 years ago.”

    Based on these and other recent findings, the idea that organisms have ways of speeding their evolution by boosting their genetic variability is generating increasing excitement among a group of cell and molecular biologists. Within the past 2 years, for instance, researchers have unearthed molecular clues that could help explain apparent increases in genetic variability not only in bacteria but in eukaryotes as well. “I think it's very cool stuff that, amazingly, not enough people have really gotten the scoop on,” says Rosenberg.

    But a number of evolutionary biologists are trying to put the brakes on this mounting enthusiasm. Although the critics say the new molecular findings are intriguing, they question their origins and role in evolution. Specifically, these biologists say it is uncertain whether these processes were selected for their ability to generate variability in the first place. Nor is it clear whether they accelerate long-term evolution. Because most mutations are harmful, increased variability may often be costly to individuals and species. “It is hard to see how selection would directly favor a process that generated random variation or even one that just preserved it,” says evolutionary biologist Jon Seger of the University of Utah in Salt Lake City.

    Thus, a spirited tussle has ensued as researchers from these two camps put forth their interpretations of the new molecular findings. With roots dating back to Charles Darwin in the mid-1850s, the question of whether organisms harbor systems for adjusting their own rate of evolution remains open.

    Error-prone enzymes

    For decades, most biologists have worked under the assumption that mutation rates are constant and that individual organisms passively submit to the forces that shape evolution. Yet the idea that organisms may modulate their genetic variability has surfaced from time to time. Even Darwin suggested in The Origin of Species that environmental changes resulting from animal domestication affect variability.

    But that didn't prepare members of the biological community for the jolt they received in 1988, when molecular biologist John Cairns and his colleagues at the Harvard School of Public Health published in Nature an even more shocking idea than Radman's. Cairns proposed that, depending on their environmental conditions, bacteria might be able to direct mutations to particular genes. The dogma-shattering idea that mutations might not be completely random “touched a raw nerve,” says Cairns. It smacked of “Lamarckism”–a reference to Jean-Baptiste Lamarck's now-discredited theory that species evolve through the inheritance of characteristics acquired during an organism's lifetime. Outraged, a number of evolutionary biologists quickly embarked on their own studies to test the notion. The flurry of studies ultimately revealed that Cairns's original proposal was untenable, and the community, including Cairns, now at the Radcliffe Infirmary in Oxford, United Kingdom, discarded it.

    Bacterial lunch.

    Adaptive mutations allow a strain of E. coli to feed on lactose assessed by a blue indicator dye (solid blue colonies on right). Bacteria can also acquire this ability by amplifying the lactose-digesting genes, a temporary phenomenon (left).


    Thanks to the commotion it ignited, however, Cairns's article prompted the study of a new phenomenon: the increased mutation rate observed in Escherichia coli during times of stress—in particular, starvation. Most of the evidence for this phenomenon comes from studies of a strain of E. coli that carries a mutation inactivating the lac operon, a group of genes that allow bacteria to digest lactose. When cells have plenty of food choices, they rarely acquire mutations that counteract the lactose deficiency. Yet, as Cairns and Foster described in the journal Genetics in 1991, when lactose is the only choice on the menu, rates of these compensating mutations skyrocket.

    Over the past decade, researchers have been dissecting the molecular underpinnings of these so-called adaptive mutations. And within the last 2 years, they have made impressive strides. They have found, for example, that although these mutations are not directed to particular genes, as Cairns originally suggested, they don't uniformly pepper the bacterial genome either. “There are hot and cold regions for hypermutation,” says Rosenberg, who is now working on defining these regions. “All regions are not equal.”

    One of the most exciting findings has been the discovery of the error-prone polymerases. “It's a great novelty,” says Radman. “We knew of these E. coli genes for over 20 years but couldn't recognize them as polymerases.” That changed in 1999, when researchers found that these proteins could copy lesioned DNA in a test tube.

    Microbiologists already knew that when bacteria suffer DNA damage, they switch on a response, called SOS, that arrests the cell cycle and turns on genes that repair DNA and allow its duplication. They suspected that these genes might help regular polymerases avoid getting stuck when they run into a damaged stretch of DNA. But by monitoring the activities of the SOS- induced proteins in a test tube, three independent groups discovered that instead of helping regular polymerases, these proteins were polymerases themselves, capable of copying less-than-perfect DNA.

    These SOS polymerases appear to help cells produce DNA when high-fidelity enzymes can't. In an article published in 1995 in the Proceedings of the National Academy of Sciences (PNAS), Radman and colleagues provided evidence suggesting that starvation could activate the SOS response. And last year, Rosenberg reported in PNAS that efficient adaptive mutation requires RecF, a protein that helps induce the SOS response, as well as other proteins produced during the SOS response. So researchers began to suspect that starvation might activate the SOS response, turning on error-prone polymerases, which results in an increase in the number of mutations. Foster cautions that this scenario has yet to be unequivocally proven. But her results, published last spring in the proceedings of the 65th Cold Spring Harbor Symposium on Quantitative Biology, and Rosenberg's study in the March 2001 issue of Molecular Cell show that the error-prone polymerase IV is indeed responsible for many adaptive mutations.

    This is important, says Rosenberg, because it provides the molecular basis for a potential path for the rapid evolution of new traits. “Everybody in the field [of adaptive mutation] is really excited,” says Foster.

    In a 1999 Nature News and Views article, Radman, one of the chief proponents of this view, enthusiastically described the role—at the time, merely suspected—of the error-prone polymerases in adaptive mutation and dubbed them “mutases.” These mutases, he said, are “enzymes designed to generate mutations”–implying that they had been selected for this explicit purpose during evolution.

    Not so fast, said a number of evolutionary biologists, including Joe Dickinson of the University of Utah. Dickinson was particularly critical of Radman's assertion because he failed to distinguish between the purpose of the enzymes and their effects. “There's a sad history in evolutionary biology of people not making careful distinctions and therefore getting lured into sloppy thinking,” he says.

    Radman now agrees with Dickinson that whether the error-prone polymerases were selected during evolution for their ability to generate mutations remains far from certain. Still, Dickinson chides Radman and others studying adaptive mutation for giving scant attention to the alternatives. For instance, error-prone polymerases may have been selected for their ability to allow cells to cope with damaged DNA; the generation of variability may be simply a nonselected byproduct. It's also possible that when cells are stressed, they can't afford the cost of high-fidelity DNA synthesis. “The cells may be turning the lights off to keep the whole system from crashing, just trying to hang on,” says evolutionary geneticist Paul Sniegowski of the University of Pennsylvania in Philadelphia. What's more, say Sniegowski and others, conjuring scenarios in which evolution selects and maintains elevated mutation rates is not easy (see sidebar on p. 1826).

    The molecular biologists counter that even if increased mutation rates did not evolve for the purpose of tuning evolution, the diversity it generates could nevertheless act as an engine of change. And if this is the case, increased mutation rates could allow organisms to accelerate evolution when times get tough.

    Evolutionary fast track

    Susan Lindquist, a cell and molecular geneticist at the University of Chicago, shares this view. She recently discovered processes in eukaryotes—not just simple bacteria—that she proposes could provide evolutionary fast tracks in times of stress. “The main point is that, no matter how they arose, [these processes] provide a plausible route to the evolution of new traits,” she says.

    Multiple mutations.

    Increased mutation rates also crank up nonadaptive mutations. In a population of E. coli that have acquired adaptive mutations for feeding on lactose (red and white cells), some cells (white) also bear mutations in genes required for feeding on maltose.


    One of these processes involves a yeast protein, Sup35, that helps terminate protein translation—the process by which proteins are generated using messenger RNA (mRNA) as a template. Researchers have known that Sup35 sometimes changes its shape and turns into a prion—a protein that self-propagates by causing other Sup35 proteins to misfold and that can be passed from parent to daughter cells. In this prion form, known as the [PSI+] prion, the protein fails to perform its job properly. That, in turn, causes the translation machinery to miss stop signals in the mRNA and create proteins with extra segments.

    Lindquist and her Chicago colleague Heather True wanted to see whether this increased variability could help the organism cope with a stressful environment, as others have proposed for the elevated mutation rates of starving E. coli. To find out, they compared the growth of yeast harboring either the normal protein or the prion under a wide variety of conditions, including different food sources, a range of temperatures, and exposure to toxic drugs. As they reported in the 28 September 2000 issue of Nature, in nearly half of 150 tests, the prion affected growth—boosting it in over a quarter of these cases.

    Given that random increases in variability, such as the random disruption of single genes, usually squelch growth, the prion's effects were surprisingly beneficial. And Lindquist thinks they may be an evolutionary boon. Nobody knows exactly what triggers the Sup35 protein to switch to its prion conformation. But in a typical yeast population, roughly one cell in a million does. So in large yeast populations, there are probably always a few members that sport new, heritable traits, says Lindquist. If the environment is static and does not favor these traits, these few anomalous organisms will die out. But in a fluctuating environment—say, a vineyard where food and warmth are plentiful in summer but not in winter—the prion could be a source of useful variations, enabling at least a few of the organisms to survive. Those, in turn, would be selected for in classic Darwinian style, the researchers propose. The population wouldn't be ultimately overrun by prions, however, because the prion spontaneously flips back to its nonprion shape.

    Evolutionary biologist Nicholas Barton of the University of Edinburgh, for one, questions that interpretation. “It is not surprising that the prion should sometimes increase growth rates in environments to which the yeast is not well adapted,” says Barton. But “without knowing how the yeast lives in nature, it is hard to assess the significance of this one intriguing example.”

    But there's a bigger problem, Barton and other evolutionary biologists say. Most random mutations are deleterious, so how could processes that boost variability help organisms survive overall? In fact, says Barton, “a major problem in evolutionary biology is to explain why genetic variation is so abundant in nature.”

    One researcher who has examined the benefits and costs of genetic variation is Richard Lenski, a microbial ecologist at Michigan State University in East Lansing. In a series of experiments, his team created high-mutating bacteria and low-mutating bacteria in identical environments to see which adapted faster. To create populations with different mutation rates, Lenski's team inserted gene variants encoding deficient DNA repair enzymes into repair-proficient bacteria. They then monitored the bacteria's increase in fitness over thousands of generations.

    In a few circumstances, elevated mutation rates provided their owners with an adaptive edge, the group reported (Science, 15 January 1999, p. 404). Members of very small populations, for example, sometimes fared better when undergoing high mutation rates, presumably because their chances of acquiring a beneficial mutation at normal mutation rates were exceedingly low. But in other cases, higher mutation rates did not accelerate the pace of evolutionary adaptation. “What they found is that strong benefits will be observed only under special circumstances,” says Penn's Sniegowski.

    Two research teams led by François Taddei at the French biomedical research agency INSERM in Paris and Michel Fons at the French Institute for Agronomy Research in Jouy-en-Josas have performed competition experiments to examine the costs and benefits of increased mutation rates. They inoculated mice with control E. coli and with a strain sporting a high mutation rate due to a defective DNA-repair enzyme. Even when the control bacteria outnumbered the mutators 50 to 1 in the initial inoculum, the mutators quickly outgrew the controls within a few days, they reported (Science, 30 March, p. 2606). Yet over time, the mutators lost their edge and could not keep pace with the controls when nutrients were scarce, the in vitro experiments showed. And when the researchers monitored the transmission of these bacteria between hosts, the controls outperformed the mutators. The researchers speculate that the high mutators accumulated deleterious mutations that weakened their chances of survival as they encountered nutrient-poor environments in their travels between hosts. In short, elevated mutation rates seem to provide benefits only under certain circumstances, and mostly in the short term.

    But these tests are far from definitive on the evolutionary benefits and drawbacks of enhanced genetic variability—in either starving bacteria or prion-carrying yeast. Barton and evolutionary biologist Linda Partridge of University College London think more competition experiments, such as those performed by Taddei, are needed.

    To gain a full picture of the evolutionary implications of these processes, however, theoretical studies will also be necessary, asserts Partridge: “There's actually a huge pedigree of theory that would enable one to analyze this formally.”

    Working up estimates of the costs and benefits of mutation in bacteria under various conditions is one important step in that direction. Previous studies have suggested the frequencies at which beneficial and deleterious mutations arise. Now Sniegowski is planning to factor in the cost of DNA synthesis fidelity to see how much this could contribute to the selection and maintenance of baseline mutation rates. This approach might also help researchers studying adaptive mutation. Enhanced variability is not the only potential benefit of increased mutation rates; another benefit might be a reduced cost of maintaining high fidelity. So systems that crank up their mutation rates may persist because of their cost- reducing benefits rather than their variability-generating abilities.

    “One way to think of the cost of fidelity is that its impact depends on the current economics of a population,” says Sniegowski. If maintaining high-fidelity DNA synthesis is pricey, then cells under stress might be unable to afford it.

    Drawing on the combined wisdom of theory and experiment, such approaches might help sort out some of these unresolved questions. And the increasing interest in evolvability may spark additional approaches. Evolutionary biologist Christopher Wills of the University of California, San Diego, for one, is enthusiastic about the possibilities: “I'm very glad that the evolution of evolvability is finally starting to catch people's attention.”


    Why Evolution Might Not Favor Increased Genetic Variability

    1. Marina Chicurel

    Evolutionary biologists are often stymied when they try to imagine the evolution of mechanisms designed to increase genetic variability. One reason is that such mechanisms can only be selected indirectly, through the beneficial mutations they create.

    For example, if a population of bacteria encounters a deadly antibiotic, only those that have mutations allowing them to survive the toxic effects of the drug will thrive—and those aren't necessarily the same bacteria as those with increased mutation rates, explains Richard Moxon of the John Radcliffe Hospital in Oxford, United Kingdom. Admittedly, bacteria with increased mutation rates may have a better chance of acquiring resistance mutations, but selection acts directly only upon the resistance mutation, not the mutation generator. In other words, mutator mechanisms can only persist by hitchhiking with the beneficial variants they produce.

    An elevated mutation rate can't be maintained in a population simply because of its promise to provide beneficial mutations in the future. “Evolutionary selection lacks foresight,” says Joe Dickinson of the University of Utah in Salt Lake City.

    And in sexual organisms such as yeast, generators of variability face an additional obstacle. In asexual bacteria, a genetic variation coding for an elevated mutation rate can travel for several generations with the beneficial mutation it generated; the two genes are said to be linked. By contrast, in sexual organisms, linked genes can be separated through a process called recombination, which reshuffles the genetic deck every generation. Consequently, any two given genes are not necessarily inherited as a pair, just as two adjacent cards may or may not remain together after shuffling.

    So, in sexual organisms, the chances are low that generators of variability will remain associated with their beneficial mutations for several generations. And once a generator is separated from favorable mutations, natural selection is likely to act against it because of the more common deleterious mutations it causes. “That's a problem that anybody who thinks about the theoretical concept of a mutator, and the proposal that it can be advantageous, has to deal with,” says Moxon. “And that's a very serious objection.”


    A Former Capital Stakes Its Future on Science

    1. Robert Koenig

    Most of the politicians have left for bustling Berlin, but scientists are hoping to keep Bonn from becoming a post-Cold War backwater

    BONN—When reunified Germany moved its capital back to Berlin a few years ago, this placid city seemed poised to fade into obscurity. Instead, Bonn is seeking to redefine itself as one of the country's foremost science cities. Last week, the cornerstone was laid for a $100 million edifice, the Center of Advanced European Studies and Research (CAESAR), which is now rising on the banks of the Rhine. Bonn's 183-year-old university, once known primarily for its law and liberal arts faculties, has been pouring resources into its medical and natural sciences departments. The federal government's science and education ministry and the main research granting agency, the Deutsche Forschungsgemeinschaft (DFG), have remained in Bonn rather than joining the exodus to Berlin, and the city is now home to several international science secretariats. Bonn is also busy refurbishing a collection of unique science museums. All this is intended to breathe more scientific life into a place that, even in the depths of the Cold War, novelist John le Carré dismissed as “a small town in Germany.” But Bonn's ascension is by no means assured: It faces stiff competition from established science bastions like Heidelberg and Munich, as well as upstarts in the east such as Dresden and Leipzig.

    Bonn's venerable university is spearheading the basic research end of this attempt to take on the rest of Germany. The university now houses Europe's most advanced center for epilepsy research, and it is considering a proposal to build a $35 million “Life and Brain Center” that would promote collaborative neurobiology projects between academia and industry. “The idea is to build on a U.S.-style model that would bring together basic researchers, the neurological medical sciences, and the biotech industry,” says Bonn University neuropathologist Oliver Brüstle, who has become one of Germany's most controversial and outspoken scientists since his research team submitted the first application in Germany to import embryonic stem cells for nerve-cell regeneration research (see p. 1811).

    Brüstle, who spent 4 years at the U.S. National Institutes of Health, says he sees great potential for Bonn as a research center—as long as Germany's political and scientific establishments permit the sort of research that needs to be done. The political turmoil over Brüstle's stem cell research—which the DFG has approved in principle, but the German government is now debating—is in some ways emblematic of the problems that Bonn and other German research centers face. University research is often impeded by excessive bureaucracy, and the research and education ministry has been stymied in some of its efforts to make research more flexible.

    Renovating and innovating.

    Bonn University's main building and artist's conception of CAESAR (below).


    CAESAR is trying to buck these hidebound research traditions. “We want to become Germany's leading example of high flexibility in research,” says CAESAR's scientific director, applied mathematician Karl-Heinz Hoffmann. Even though the center is government-funded, it does not operate under rules that bog down research and clog turnover at most German institutes. Scientists are hired on 5-year contracts, for example, and are required to finish their research projects within that time.

    For now, CAESAR's 70 scientists are housed on the upper floors of an office building in Bonn's old town, not far from the birthplace of composer Ludwig van Beethoven. Over the next 2 years, after the center's new headquarters and labs are finished, CAESAR will expand to about 300 researchers in fields ranging from biology to computer science.

    CAESAR, whose acronym recalls the Roman general who invaded the Rhineland 2000 years ago, is aiming to conquer a far different territory: emerging markets in fields such as nanotechnology, “smart materials,” and biosensors. For example, CAESAR has teamed Michael Moske's solid state physics group with Beate Schmid's molecular biology group to develop “microbalances”– resonant quartz sensors that use nucleic acids to help detect minute changes caused by modulations of mass. Other groups are developing materials that aim to improve the links between human and machine, such as connecting electronic devices with nerve cells or other human tissues.

    As CAESAR probes the human-machine interface, other institutions in Bonn are serving as Germany's interface between science and policy-making. Last year, the DFG added a $20 million wing to its Bonn headquarters, signaling a long-term commitment to the city, and the research ministry has also kept its main building here. In addition, the two most important centers for expanding German academic and scientific influence abroad—the Alexander von Humboldt Foundation and the German Academic Exchange Service—are housed in Bonn. They recently benefited from an extra $82 million in federal grants to bolster their programs to attract top scientists to Germany (Science, 9 March, p. 1876). Also striking an international note, the United Nations has established five secretariats in Bonn, including those overseeing conventions on climate change, desertification, and the preservation of migrating species.

    Hailing CAESAR.

    Scientific director Karl-Heinz Hoffmann sees strength and flexibility.


    Across town, the Max Planck Institute for Radio Astronomy held an open house last month that drew nearly 6000 visitors to mark the 30th anniversary of its 100-meter radio telescope in nearby Effelsberg. Billed as the world's largest moveable radio telescope, it has helped the institute's scientists learn about the early development of the universe by analyzing pulsars, quasars, and distant galaxies. And Bonn is bringing science to the public as well. The science-oriented Deutsches Museum Bonn, for example, is putting on a major exhibit this year, in coordination with the Smithsonian Institution in Washington, D.C., on the history of the Nobel Prizes. Farther down Bonn's “museum mile” is the Museum Alexander Koenig, a century-old zoological institute that is expanding (see sidebar).

    From his vantage point in the hothouse of Bonn's 200-year-old Botanical Garden, botanist Wilhelm Barthlott views Bonn as an ideal place for scientists to pursue research and to find ways to apply it. He should know: Industry beat a path to Barthlott's door after he and a colleague explained the “lotus effect”–how the leaves of the lotus and related species, which have a rough and complex surface structure studded with wax crystals, are so good at keeping themselves clean. A host of “lotus effect” products—such as self-cleaning paint and Teflon-like pan coatings—are now on the market. Today, Bonn itself is aiming to become a hothouse for German science—although it may be a few years before that ambition takes firm root.


    Zoology Institute Shakes Off the Dust

    1. Robert Koenig

    BONN—The Museum Alexander Koenig has long been a taxonomist's dream but a bench researcher's nightmare: scientists jammed into cramped basement labs, having to elbow their way past stuffed giraffes and antique wooden cases packed with desiccated birds or formaldehyde-soaked snakes. But the century-old museum, which began as the vision of the Bonn University ornithology professor for whom it is named—a researcher who amassed Europe's largest collection of species of stuffed birds—is now being transformed into a modern research center. These days, DNA sequencers are more important than formaldehyde, and global biodiversity research is pushing aside old-fashioned expeditions to bag trophies.

    Now undergoing a $14 million renovation and expansion, the present building of the Museum Koenig was finished just before World War I broke out; it was converted to a field hospital during the war and afterward a barracks and prison. It reopened as a zoological museum in 1934; then Nazi minister Hermann Göring tried to turn it into a hunting museum. Its basement was again converted to a hospital during World War II, and afterward the museum was co-opted by the West German government, briefly housing the offices of the first postwar chancellor, Konrad Adenauer. It wasn't until the 1950s that the museum was able to reassemble its collection and return in earnest to research.

    Young at heart.

    Like other Bonn institutions, the Museum Alexander Koenig is pouring money into modernization.


    Officially a zoological research institute, the museum was also designated an Institute for Terrestrial Biodiversity in 1997—connecting it to a worldwide biodiversity research network—and it was the first German museum to establish its own molecular biology lab for speciation research. Its 15 full-time researchers keep the Global Register of Migratory Species, and they coordinate the Biodiversity Monitoring Transect Analysis (BIOTA) project for East Africa, focused mainly on Kenya. “We are setting up biodiversity observatories and measuring the impact of humans on that diversity,” says Jörn Köhler, a biologist with the museum's BIOTA program.

    Nearby, in a workroom packed with lizard cages, renowned herpetologist Wolfgang Böhme lords over an extensive collection of reptile and amphibian species. He recently succeeded in tracking down a population of dwarf crocodiles—believed for years to be extinct—that lives in the deserts of southeastern Mauritania. In addition, he and a colleague verified an extinct giant lizard species, Celestus occiduus, by examining the stomach contents of a preserved lizard collected in Jamaica in 1851.

    In another jammed lab on the museum's lower floor, evolutionary biologist Bernhard Misof's research group is conducting phylogenetic studies to better understand the startling burst of speciation of killifish in ponds and creeks in the Central African rainforests. His group also is studying speciation processes of other animals, including skinks, amphibians, dragonflies, and butterflies. “We were the first museum in Germany to establish its own molecular biology lab,” boasts Misof, whose equipment includes DNA sequencers and protein electrophoresis instruments. With the museum expansion project and the blossoming of Bonn as a science city, he says, “there is great potential here.”