# News this Week

Science  12 Nov 1999:
Vol. 286, Issue 5443, pp. 33
1. GENETIC DISEASE

# Storm Brews Over Gene Bank of Estonian Population

1. Lone Frank*
1. Lone Frank is a writer in Copenhagen, Denmark.

Tallinn, Estonia—The Icelanders do it, the Swedes do it, and now the Estonians want to do it: A group of Estonian geneticists is hoping to catalog information on the health status and genetic makeup, or genotype, of more than 70% of Estonia's population of 1.4 million. The researchers, who have organized themselves under the auspices of a not-for-profit organization called the Genome Center Foundation, presented the plan late last month to the Estonian government and the scientific council of the University of Tartu. Over the next 10 years, they propose to collect extensive health questionnaires and blood samples and commit the information to a database that will be used for research as well as individual health care purposes.

The Genome Center estimates that collecting data on 1 million people will cost $90 million to$150 million over 10 years, but it expects that more than half the costs will be covered by companies buying rights to use the data for genetic research. The project is already gathering considerable momentum: According to the Genome Center, the approval won last month by the scientific council sends out an important signal, as Tartu University is home to the country's only medical faculty. The government also reacted favorably, naming the gene bank proposal one of three large-scale national projects to receive state funding next year. Chair of the Genome Center Jaanus Pikani says this government funding will help the team refine its methods of data and sample collection, prepare legislation to win formal parliamentary approval, and inform the public about the project. Assuming that governmental and public approval is forthcoming, the researchers hope to begin gathering data and sampling blood from consenting Estonians by 2001.

But the proposal may not get an easy ride: As news of the plan begins to leak out, it is provoking a heated reaction in some medical circles. “With an underfunded health care system and a population that would benefit more from a focus on lifestyle factors, such as smoking and abuse of alcohol and drugs, we should not enter into expensive high-tech endeavors,” says Tiina Tasmuth, a professor of medical education at the University of Tallinn.

Andres Metspalu, a professor of biotechnology at the University of Tartu and a key figure in developing the idea of a gene bank, says there are two main goals: One is to identify disease genes, particularly those involved in multifactorial diseases—such as asthma and heart disease—by comparing genotypes within a group of patients with a given disease. The second goal is to set up a health care database that would give Estonians access to their own data, so they can benefit from the personalized medicine of the future. “Medical treatment will increasingly be tailored to specific genotypes, and this database would allow individuals to gain knowledge of disease risks and to receive the most effective medication,” says Metspalu. His colleague, geneticist Toomas Veidebaum of Tallinn's Institute for Experimental and Clinical Medicine, adds that it is “necessary for us to start implementing modern technologies if we are not to fall hopelessly behind.”

The disease pattern of the Estonian population is quite similar to that of Western Europe in general, but Metspalu is not concerned about overlap with other genomic projects. “With 80,000 genes to discover, and with the multigenic nature of many diseases, optimal results will come from coordination of various projects,” he says. The Genome Center team is seeking to collaborate with the Icelandic company deCODE Genetics, which has recently embarked on a similar project. DeCODE president and former Harvard University geneticist Kari Stefansson told Science he is open to collaboration, adding that “the idea behind the Estonian project is interesting, and although specifics have not been discussed, I think working together would allow us to solve some technical problems and explore possible synergies.”

But deCODE's experience does not bode well for the Estonians. Stefansson's project provoked fierce debate in Iceland and around the world. Researchers, medical ethicists, and data-protection specialists in many countries unsuccessfully lobbied the Icelandic government last year not to pass a law giving deCODE access to the health records of the entire country (Science, 1 January, p. 13). Since then, some physicians and patients have refused to cooperate in building up deCODE's database.

Some critics question whether the issues raised by the Estonian proposal will be fully addressed. “Creating an informed public debate about the ethics of genetics is a major challenge, because our countries have not yet developed the professional bioethics seen in the West,” says Eugenijus Gefenas of Vilnius University, chair of the Lithuanian National Committee on Biomedical Ethics. The “paternalistic tradition” of the postcommunist Baltic states makes it difficult to ensure that informed consent and nondirective counseling of individuals are carried out properly, Gefenas says. “[It is] irresponsible to provide genetic information that may have profound implications for the individual as well as family members and unborn children” if it may not be properly understood, adds Tasmuth.

Tasmuth says she is outraged that the researchers presented the proposal to the government before there had been any public debate. She has published an article about it in an Estonian daily newspaper, and Genome Center researchers have been invited to discuss the proposal at a meeting on 13 November arranged by the Estonian Christian Physicians' Society, of which Tasmuth is head. Metspalu recognizes the need to educate Estonians about genetics, but he believes that obtaining informed consent will not be a problem. “In a small pilot study, questioning 111 people resulted in a 90% acceptance rate, and I expect something similar for the general population,” he says.

2. INFECTIOUS DISEASES

# Malarial Genome Comes Into View

1. Elizabeth Pennisi

In 1986, Thomas Wellems set out on a seemingly narrow quest. He wanted to find the gene that enabled the malarial parasite Plasmodium falciparum to become resistant to chloroquine, the drug that had been a mainstay therapy for decades. But along the way, Wellems, a malaria expert at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, accomplished what may be a more far-reaching feat. As reported on page 1351, he and his colleagues from NIAID and from the National Center for Biotechnology Information pinpointed a series of genetic landmarks across the entire 14-chromosome genome of this deadly parasite. It is one of two new maps of the parasite unveiled this month; the second, published in the November issue of Nature Genetics, shows a different type of landmark.

Richard Hyman of the Stanford DNA Sequencing and Technology Center in Palo Alto, California, says that the new maps will be “really useful” for researchers working to sequence the parasite's genome, because the landmarks will enable them to align short stretches of sequenced DNA in the correct order along P. falciparum's chromosomes. Producing that sequence is a top target, Hyman notes. There's no preventive vaccine for malaria, which kills about 2 million people a year, and in the past 2 decades the organism has become resistant to other key antimalarial drugs in addition to chloroquine. The completed sequence may reveal potential targets for antimalaria vaccines or drugs.

A sequenced genome seemed an impossible dream when Wellems first started his project. “At the time, we didn't even know how many chromosomes there were,” he recalls. He and his colleagues planned to home in on the location of the chloroquine-resistance gene by identifying genetic landmarks in the genome and seeing which of them were inherited along with the drug resistance. The team did this by tracking down microsatellites, short, easily identifiable bits of repetitive DNA that could serve as these landmarks.

For that effort, they also spent more than 5 years developing new resistant and sensitive parasites and then cross-breeding them. Only then could they trace the inheritance of the markers and the drug-resistance trait in the offspring of the hybrids to glean clues to the gene's location.

The map naturally emerged from this effort, as the group determined the patterns of microsatellites in the offspring of the crosses. Markers that are close to one another on a chromosome are more likely to be inherited together than those far apart, and so the team could establish the relative orders of the markers—901 in all—along the chromosomes and the approximate distances between them.

The second map, produced by David Schwartz of the University of Wisconsin, Madison, and his colleagues, pins down the physical locations of its markers. These researchers used a technique called optical mapping, which Schwartz devised while at New York University (NYU) in New York City. It uses electrostatic forces to hold pieces of fluorescently labeled P. falciparum DNA stretched out on glass. Then, for this map, the researchers treated the DNA sequentially with two enzymes, each of which cuts it at different, specific sites, leaving the DNA fragments lined up in the right order.

After each enzyme treatment, the researchers measured the fragments. They put DNA pieces of known lengths on the slide for reference and used fluorescence microscopy to digitally image the DNA fragments. Finally, a sophisticated computer program developed by NYU's Bud Mishra and Thomas Anantharaman compiled the map showing the cut sites. “It's a brilliant [approach],”says Wellems.

The payoff will come as an international team completes the actual sequence of the parasite's genome, and later, as new genes are found with the help of the genetic map. In genome sequencing, researchers first generate lots of tiny, overlapping bits of DNA, then they assemble them in the right order along the chromosomes to get the full genome sequence. Now, they can use the locations of the cuts and of the microsatellite markers to figure out where newly sequenced DNA belongs along the P. falciparum genome. “They provide a scaffolding of sequence that we can use as a reference,” says Leda Cummings, a molecular biologist who is sequencing the parasite's DNA at The Institute for Genomic Research in Rockville, Maryland.

Indeed, with the help of these and other maps, the sequencers expect to finish the malarial genome by the end of 2001. Wellems predicts that with this sequence and the many other experimental resources that are becoming available (see p. 1251), the parasite's secrets “are going to unroll very rapidly.” As for the chloroquine-resistance gene that sparked the map work? It's been found, says Wellems, and its identity will soon be published.

3. PUBLISHING

# Kennedy Named Editor-in-Chief of Science

Donald Kennedy, president emeritus of Stanford University and a former commissioner of the Food and Drug Administration (FDA), has been appointed the next Editor-in-Chief of Science. A neuroscientist by training, Kennedy is currently Bing Professor of Environmental Science at Stanford.

Kennedy's appointment was announced on 9 November by the board of directors of the American Association for the Advancement of Science, which publishes Science. Board chair M.R.C. Greenwood, chancellor of the University of California, Santa Cruz, said in a statement: “He brings to this task a broad understanding of current science issues, a wealth of experience in government and university, and incomparable insight.” He will take over the editorship on 1 June 2000 from Floyd Bloom, who announced last year that he would not seek a second 5-year term when his current appointment expires in May 2000. Kennedy will retain his Stanford faculty position through the 2000–01 academic year.

Kennedy, 68, received A.B. and Ph.D. degrees from Harvard and joined the Stanford faculty in 1960. His research focused on invertebrate neurobiology, in particular on how organisms generate and control patterned motor output. He served as FDA commissioner from 1977 to 1979, returned to Stanford as provost, and was appointed president in 1980, a position he held for 12 years.

His current research and teaching focuses on environmental policy. He co-chairs an interdisciplinary center at Stanford that explores the development of policies on issues such as land-use changes, shifts in agricultural practices, and global climate change.

4. NEUROBIOLOGY

# Key Brain Receptor Gets an Unusual Regulator

1. Ingrid Wickelgren

A team of researchers at The Johns Hopkins University School of Medicine has unearthed a strange new regulator of nerve cells—a looking-glass molecule not previously known to be made by higher mammals. In the 9 November Proceedings of the National Academy of Sciences, neuroscientist Solomon Snyder and his colleagues report that they have cloned a brain enzyme that makes the amino acid D-serine, rounding out their case that this unusual molecule plays a central role in learning and memory.

Snyder's team had previously implicated the amino acid as an activator of the so-called NMDA receptor—a molecule with pivotal roles in learning, brain growth, and brain cell death. But as Snyder himself concedes, the idea that D-serine acts on the NMDA receptor was so radical that people “paid no attention” to it. For one, the NMDA receptor was supposed to be activated by the neurotransmitter glutamate in partnership with another amino acid, glycine. For another, D-serine would be an extraordinary glutamate partner indeed as “D,” or right-handed, forms of amino acids were not supposed to be made by mammals.

But cloning the enzyme that makes D-serine proves that the amino acid is made in the brain. Snyder's team went on to trace the enzyme to the same cell type, astrocytes, and the same brain areas where D-serine is found. And to nail their case, they showed that destroying D-serine in the brain greatly reduces NMDA receptor activity. “It's a significant advance,” says neuroscientist Joseph Coyle of Harvard Medical School in Boston. “They've now characterized at a molecular level a key new participant in NMDA receptor function.”

Medicine should also benefit, as the newly cloned enzyme, called serine racemase, provides a novel target for drugs to treat a range of neurological conditions in which NMDA receptors play a role. Drugs that block or quiet the enzyme, for example, might be used to quell anxiety and epilepsy and prevent damage from strokes, which can be caused by excessive activity at NMDA receptors. On the other hand, stimulating serine racemase might improve schizophrenia symptoms, which are partly caused by depressed NMDA receptor function.

Snyder became intrigued with D-serine in the early 1990s, after stumbling across an obscure paper by scientists at the National Institute of Neuroscience in Tokyo, who had detected the amino acid in rat brains. Although the rats might have acquired it from their food, Snyder thought its presence might be more than accidental. He noted that the Tokyo team had found D-serine in brain areas rich in NMDA receptors, and that other workers had shown that the amino acid stimulates the receptor in slices of brain tissue.

To follow up on his hunch, Snyder put his then-graduate student, Michael Schell, to work making antibodies to D-serine to use for mapping its brain distribution more precisely. Applied to brain slices, the antibodies homed in on the D-serine, showing that it is indeed closely juxtaposed to NMDA receptors. The researchers also discovered, to their surprise, that the cells housing D-serine are not neurons but “supporting” cells called astrocytes, and that glutamate could spur D-serine's release from those astrocytes. From those findings, reported in 1995, the researchers surmised that when a neuron dumps glutamate into a synapse, the transmitter not only sticks to the NMDA receptor but simultaneously triggers the release of its coactivator, D-serine, from an adjacent astrocyte.

The evidence for this offbeat theory was still circumstantial, however, so Snyder set out to find proof. To nail D-serine's origin to the brain, Snyder's postdoc, Herman Wolosker, went after the enzyme that makes it, serine racemase. He first purified the enzyme from rat brain, a tour de force completed earlier this year. And now, Wolosker, Snyder, and Seth Blackshaw have cloned the gene for serine racemase and shown that it is active in the same astrocytes that harbor D-serine, making D-serine's role in the brain hard to dispute. “The paper is extremely tight,” says neuroscientist Gavril Pasternak of the Memorial Sloan-Kettering Cancer Center in New York City. “It all fits together nicely.”

In as yet unpublished work, Snyder and his colleagues, Jean-Pierre Mothet and the University of Chicago's Angele Parent, added a final buttress to the case by showing that the brain's D-serine really does act on the NMDA receptor. They applied D-amino acid oxidase, an enzyme that degrades D-serine, to rat brain slices and cell cultures. As predicted, the enzyme drastically reduced NMDA receptor transmission.

Still to be determined, however, is exactly what role D-serine plays in the brain. For example, neuroscientists will want to know whether it will totally supplant glycine as glutamate's coactivator of the NMDA receptor, and if not, how the two share the job. But by uncovering this surprising new neuronal regulator, Snyder's team has pointed scientists toward original ways of tinkering with and exploring the mind.

5. COSMOLOGY

# Balloon Flight Brings Cosmic Glow Into Focus

1. Robert Irion

Seven years ago, the Cosmic Background Explorer (COBE) satellite thrilled cosmologists by revealing subtle temperature ripples in the faint microwave glow that pervades the universe. The ripples were the first glimpse of imprints left on the young universe during its birth in the big bang. But COBE could only view great chunks of the sky at once, so the fine details of the ripples remained elusive. Now, a telescope carried aloft by a balloon has scrutinized the microwave glow much more closely—giving cosmologists who have seen the early results another thrill.

The data come from BOOMERANG, a joint U.S. and Italian mission that flew over Antarctica for more than 10 days in December 1998 and January 1999. BOOMERANG's 1.3-meter telescope—soaring 36 kilometers high, above the atmosphere's moisture—zeroed in on fluctuations some 35 times smaller than COBE did. A preliminary display of the resulting temperature map sent ripples through an audience of astrophysicists at a recent meeting.* “It was a moment like seeing the COBE data for the first time,” says astrophysicist Craig Hogan of the University of Washington, Seattle. “It's the most beautiful map of the sky I've ever seen.”

BOOMERANG researchers are closely guarding their analysis until it is complete, which could take many months. But cosmologist Andrew Lange of the California Institute of Technology (Caltech) in Pasadena, the U.S. team leader, says the final results will expose the intricacies of the sky's temperature variations as never before. “We have moved into a new epoch,” Lange says. “These are the first maps in which you can actually look and point in great detail at which parts of the sky are hot and which parts are cold.” Lange and cosmologist Paolo de Bernardis of the University of Rome, La Sapiènza, who leads the Italian component of the team, think the tiny temperature bumps will help cosmologists pin down the proportions of matter and energy in the newborn universe.

The radiation measured by BOOMERANG and a myriad of other current and planned cosmic microwave probes is a cosmic fossil, dating from when temperatures in the young universe were so high that light and matter seethed together in an interacting soup. Small gravitational disturbances inside this plasma tried to draw the matter into clumps, but radiation pressure from the energetic photons fought back. The tug-of-war drove a series of acoustic oscillations within the fluid, much as drawing a bow across a violin's strings causes the instrument's wood to resonate at many different frequencies. Then, when the cosmos reached an age of about 300,000 years and cooled enough for energy to stream through the matter unimpeded, the photons escaped. They form the faint microwave background we see today, imprinted with the remnants of those primordial oscillations.

Cosmologists typically graph the oscillations as a function of power (differences in temperature) and angular scale (their apparent sizes on the sky). The resulting “power spectrum” resembles a roller coaster, with a high initial peak followed by ever-diminishing peaks, which mark the higher frequency overtones of the first oscillation peak. As it turns out, the details of those peaks—such as their relative heights and their precise angular scales—encode critical information about the nature of the cosmos.

For example, the first peak should fall at a scale of about 1 angular degree in a universe containing just the right density of matter and energy to make space geometrically flat, so that parallel light rays remain parallel forever. A flat universe is expected in a popular scenario of cosmic origins called inflation, which posits an extraordinarily fast expansion of space within a fraction of a second after the big bang. Other probes of the microwave background have suggested that the first peak meets this test, with varying degrees of confidence (Science, 17 September, p. 1831).

But “in order to really believe these results, we need to be able to see the higher peaks as well,” says theorist Marc Kamionkowski of Caltech. Astrophysicists who saw BOOMERANG's temperature map believe that the data will pinpoint the first and second acoustic peaks and perhaps even outline the third. Their locations could make the flatness of space unmistakable, and they could also reveal how the makeup of the universe is divided between matter and a mysterious “vacuum energy” called the cosmological constant.

Other missions will provide a check on any conclusions. A balloon mission that flew over Texas in June, called MAXIMA, may also map the first and second acoustic peaks, says cosmologist George Smoot of Lawrence Berkeley National Laboratory in Berkeley, California, who led the original COBE analysis. And next fall, NASA will launch the long-awaited Microwave Anisotropy Probe to chart the background temperature fluctuations from orbit, with unprecedented precision.

For now, says astrophysicist Rocky Kolb of the Fermi National Accelerator Laboratory in Batavia, Illinois, BOOMERANG “certainly seems to show that we live in a flat universe.” But he adds, “I'm a little worried about that, because it's the expected result. It's always easier to see what you expect.”

• *Cosmic Genesis and Fundamental Physics, Sonoma State University, Rohnert Park, California, 28 to 30 October.

6. IMMUNOLOGY

# Memory T Cells Don't Need Practice

1. Michael Hagmann

Once learned, some abilities, such as swimming or riding a bike, are never forgotten even after years without practice. Others, say running a marathon, need a regular brushing up. Immunologists have long debated which category our immunological memory falls into. Once immune cells learn to recognize a particular antigen, such as a viral protein, do they need constant reminders to stay on top of things, or are their memories permanent? Two reports in this week's issue of Science (pp. 1377 and 1381) now bolster the notion that immune cells never forget.

The immune cells in question are T cells, which spring into action to kill infected cells or orchestrate other immune responses when other cells “present” them with an appropriate antigen, together with a so-called MHC protein. The new work, which comes from two independent groups, led by Rafi Ahmed of Emory University in Atlanta and Susan Swain of the Trudeau Institute in Saranac Lake, New York, shows that memory T cells don't need to repeat this experience: They persist and maintain their ability to recognize their specific antigens, even when put into mice that have been genetically altered to eliminate the MHC proteins, which makes antigen presentation impossible.

View this table:

For many immunologists, the findings cast a final verdict on the long-standing controversy. “These two papers nail it down pretty firmly that you don't need antigen or some orthodox signaling by classical MHC molecules” to maintain T cell memory, says Peter Beverley of the Edward Jenner Institute for Vaccine Research in Compton, U.K.

Not everyone is convinced, however. Benedita Rocha of the Necker Institute in Paris, whose own work suggests a need for constant “tickling” of memory T cells by MHC molecules, says the experiments on which the findings are based are very complicated and pose many pitfalls. At best, she maintains, “the results are not conclusive yet.”

Ahmed and his colleagues worked with so-called killer T cells, which, when activated, attack and destroy certain abnormal cells, such as those infected by viruses. The team began by immunizing normal mice with the lymphocytic choriomeningitis virus (LCMV), a well-known mouse pathogen. After waiting several months until the antiviral T cell memory was established, the researchers purified the animals' killer T cells, including any anti-LCMV memory cells, and then transferred the cells into two mouse strains that had no T cells of their own. The strains were genetically identical, with a single exception. One also lacked the gene for a protein called β2-microglobulin (β2M), which helps transport the class I MHC proteins needed for antigen presentation to killer T cells to the cell surface.

As a result, T cells transplanted to these mice should get little or no stimulation by antigen-presenting cells. Yet when the researchers recovered virus-specific T cells from the recipient mice 10 months later, they found the same number of memory T cells regardless of whether β2M was present.

Rocha sees a flaw in this experiment: She suggests that the MHC class I-positive T cells might have stimulated each other. Ahmed and his colleagues tried to guard against the possibility by testing memory T cells that themselves lacked β2M, but Rocha maintains that “even these so-called MHC class I-negative T cells are not completely devoid of MHC.” Immunologist Peter Doherty of St. Jude Children's Research Hospital in Memphis, Tennessee, dismisses her doubts, however: “We don't have any evidence whatsoever that [killer] T cells can stimulate each other.”

The Emory team also showed that, far from being nonfunctional look-alikes, the long-lived memory T cells were in a “ready-to-hit” mode. When he and his colleagues restimulated the cells with viral antigens in a petri dish, they churned out the immune messenger interferon γ, an early step in the immune response, just as fast as their counterparts from MHC-bearing recipients.

The memory T cells also seemed to renew themselves continually, as more than 20% divided within a 1-week period in both MHC class I-positive and deficient mice. “That tells us that unlike naïve T cells, memory T cells have developed a new way of proliferation that is independent of either antigen or MHC,” says Ahmed.

Swain's team studied another kind of immunologic memory, that of T helper cells, so-called because they help jump-start other immune cells, including the antibody-producing B cells. Working with a genetically modified mouse strain in which almost all T cells were specific for the same antigen, Swain and her colleagues extracted spleen cells and activated them with the appropriate antigen. Four days later, presumably before memory cells had developed, they transplanted the cells into hosts that lacked MHC class II molecules, which are needed to present antigen to T helper cells.

There, the T helper cells gave rise to memory T cells that again persisted. And because the memory cells seem to have developed after the helper cells were transplanted to antigen-free mice, Swain thinks that memory is only established once the antigen has been cleared from the body. “A persisting antigen might be counterproductive” for generating T cell memory, she says, because it could push T cells into overdrive and ultimately trigger cell suicide. If so, says Beverley, promising vaccines should be designed to degrade rapidly, or else memory might not develop.

In contrast to the slow renewal of memory T cells that Ahmed's group observed, almost all of the transgenic T helper memory cells were quiescent. “They seem to persist mainly as nondividing cells, similar to the long-lived neurons of the brain,” suggests Swain.

But even though the two findings don't agree on every point, most experts are convinced that memory T cells don't need constant stimulation by either antigen or MHC molecules to stay in shape. The great unknown now is the nature of the signal—if there is one—that keeps memory T cells alive and kicking, says Ahmed: “My guess is that this work will set the stage for the next 5 years of T cell memory research.”

7. NUCLEAR CITIES

# U.S. Cuts Retraining of Russian Weaponeers

1. Richard Stone

Congress has slashed by 75% a planned expansion of an effort to produce 20,000 civilian jobs for weapons scientists and engineers in 10 closed cities in Russia. But while the Department of Energy (DOE) is reeling from the blow to its 1-year-old Nuclear Cities Initiative (NCI), European countries hope to start their own program next year to keep nuclear scientists employed—and perhaps avert a brain drain to rogue countries.

During the Cold War, the Soviet Union set up a secret network of cities to build the country's nuclear arsenal. Soon after the superpower fissioned in 1991, Russia and the United States began allowing their nuclear scientists to strike up collaborations. The pace picked up last year, after Russia's Ministry of Atomic Energy announced that as many as 50,000 workers in the nuclear cities would need new jobs in the next several years. “The cities are in desperate shape and suffering terribly,” says Jack Segal, director for nonproliferation and export controls at the U.S. National Security Council.

To stimulate job creation, DOE launched NCI last fall with $15 million. The agency modeled the effort after a program it began in 1994, the Initiatives for Proliferation Prevention (IPP), which matches U.S. national labs and companies with former Soviet weapons scientists engaged in peaceful work with commercial promise (Science, 8 January, p. 160). In February, however, the General Accounting Office reported that the$25 million IPP program was spending only 37% of its funds on former Soviet institutes and pouring the majority into the U.S.-based collaborators. More damning, the report charged that the IPP “has not achieved its broader nonproliferation goal of long-term employment” for weapons scientists but rather is keeping them afloat on R&D contracts. Given IPP's lack of success, the report concluded, the NCI “is likely to be a subsidy program for Russia for many years.” The current NCI program “is not selling and may not even be working,” says Kenneth Luongo, director of the Russian-American Nuclear Security Advisory Council (RANSAC), a private research group focused on the Russian nuclear complex.

Such doubts spelled trouble for NCI, which hoped to see its budget double, to $30 million, in 2000. Picking up on the report, the House committee that oversees DOE's budget declared “it is not clear that [DOE] is the best agency to implement this program since the most important training needed in these cities is marketing and business expertise”—not traditional strengths of the U.S. national labs. NCI was launched “with a lot of money, a lot of fanfare, and not a lot of programmatic planning,” says Madelyn Creedon, counsel for the Senate Armed Services Committee, which reviews Defense Department efforts to reduce the former Soviet nuclear threat. The House wanted to nix all but$1.5 million for NCI, but House-Senate conferees agreed to provide $7.5 million, half the current level, in 2000. “This reduced funding is absolutely insufficient to support business activity in even a single city,” says Olga Vorontsova, deputy director of international relations at the nuclear center in Sarov. Unless the program expands, she predicts, NCIwill “contribute little to the reduction of the nuclear weapons workforce.” The funding cuts mean that DOE will have to postpone plans to expand NCI beyond its three current sites (see table). DOE officials, meanwhile, have stepped up their outreach to Congress and also hope to win support from the seven other federal bodies on NCI's advisory board. “I would applaud and encourage facilitation of a team approach,” says NCIsenior adviser Terry Plummer. But DOE and the national labs “have built trust and confidence with the nuclear cities,” so the agency is “the logical home” for the NCI, says another NCI official. View this table: In the meantime, Europeans are forging ahead with their own plans for an initiative that would plow$10 millon or more a year into the cities. At a meeting later this month in The Hague, Netherlands, they will join with U.S. and Japanese representatives to identify potential projects. “It will be an attempt to prioritize unmet problems,” says Segal, and “to try to get countries to commit money.” Leading the charge for a European NCI, announced last week at a RANSAC-sponsored meeting in Washington, D.C., is the Landau Network-Centro Volta in Como, Italy, a nongovernmental organization that supports scientific cooperation with the former Soviet Union. The Landau network will follow up discussions at The Hague with its own meeting with nuclear city officials next month in Rome.

If the European effort gets off the ground, it could play a vital role in supporting the nuclear cities until NCI recovers. “It's a daunting agenda,” says Segal, “but one for which we'll never be forgiven if we fail.”

8. GENETICS

# Gene Skews Patterns of Inheritance

1. Elizabeth Pennisi

In the eyes of Mendelian geneticists, all chromosomes are created equal. In anticipation of sexual reproduction, paired chromosomes split up so that each developing egg or sperm ends up with just one of the partners. In theory, both partners have the same chance of making it into the next generation. But in mice and some fruit flies, reality is not so egalitarian. Sometimes one chromosomal partner consistently wins out over the other, seemingly breaking one of the basic rules of genetics.

Last March, researchers at the University of Wisconsin, Madison, solved part of that mystery in fruit flies. They showed that early in sperm development, while partner chromosomes are still close together, a truncated protein encoded on one copy somehow prevents pre-sperm cells carrying the other from maturing (Science, 12 March, pp. 1651 and 1742). Now mouse geneticists have fingered the gene responsible for a similar phenomenon in mice.

Last week at the 13th International Mouse Genome Conference in Philadelphia, Bernhard Herrmann, a geneticist at the Max Planck Institute for Immunology in Freiberg, Germany, described a mouse gene, located on chromosome 17, that can also skew chromosomal inheritance patterns. This gene, which codes for a protein kinase enzyme, apparently works by altering the ability of mature sperm to swim to their target, the egg. (The results also appear in the 11 November issue of Nature.)

The finding solves “one of the oldest riddles in mouse genetics,” comments John Schimenti, a molecular geneticist at The Jackson Laboratory in Bar Harbor, Maine. It might even have practical uses. Putting the gene on an animal's sex-determining chromosome can alter the sex ratio of its offspring, allowing farmers breeding dairy cows, for example, to produce almost all female calves. “You could save a lot of animals and at the same time enormously increase the productivity,” Herrmann says.

Geneticists first noticed the unequal transmission of a then-unidentified chromosome in the 1930s while studying a mutation that produces tailless mice. Mendelian genetics predicted that when the males breed with normal females, 50% of the progeny should have short tails, as a result of inheriting one mutant and one normal copy of the gene. But the crosses produced far fewer short-tailed animals. “This was the first time people saw a distortion in the Mendelian ratio in mammals,” Herrmann notes.

In 1984, Mary Lyon, a mouse geneticist at the Medical Research Council Laboratory of Mammalian Genetics in Harwell, England, took a stab at explaining this distortion after observing strange inheritance patterns of tail lengths in her breeding studies. She suggested that up to four genes had to be involved: one called the responder and as many as three others that she called distorters. She figured out that the responder reduced sperm fitness when not accompanied by distorter genes. As a result, both responder and the presumably closely linked tailless gene would be passed on less than 50% of the time. But when distorter proteins were present, Lyon predicted, the responder could counter their detrimental effects, skewing inheritance in favor of any chromosome carrying the responder. “It turns out that her model is correct,” says Lee Silver, a geneticist at Princeton University.

Silver himself had gone looking for the responder gene, working with Schimenti. But although both they and Herrmann came up with candidates for the responder gene, neither panned out. Herrmann's gene, called rsk3, provided a lead to the right one, however.

The stretch of chromosome 17 where the rsk3 gene is located has undergone several duplications and rearrangements. On a hunch, Herrmann decided to find out whether one of those rearrangements might have linked all or part of rsk3 to the true responder gene. The hunch paid off.

The responder gene Herrmann found, called Tcr, consists of the partial rsk3 gene fused to another gene that resembles genes for sperm-motility kinases, or Smoks. To make sure the new gene was the right one, the Max Planck group inserted it into various mouse chromosomes and showed that it does skew inheritance patterns. When present on the Y chromosome, for instance, the mice fathered far more than the normal 50% male progeny.

Herrmann thinks the responder gene handicaps sperm that carry it by causing their flagella to beat too slowly, while the distorter genes—whose identities are still unknown but which seem to be on the same chromosome—cause them to beat too fast. As a result, only the sperm lucky enough to get both distorter and responder proteins move optimally and are able to beat out the sperm that lack either a responder or distorter.

The discovery in flies and mice of two very different genes that promote their own inheritance—and incidentally that of the chromosome they ride on—suggests that the evolutionary pressure to become such a self-promoter must be quite strong, says Silver. Successful transmission should lead to ever greater representation of that version of a chromosome in a population. Consequently, he adds, “there's probably thousands of examples out there that we can't see,” perhaps even in people.

9. ANIMAL REGULATIONS

# FDA Report Scores Chimp Research Lab

1. Gretchen Vogel

A federal investigation has found that the country's largest chimpanzee facility has violated dozens of regulations relating to good laboratory practices. The violations, described in a preliminary report detailing the results of an August inspection by the U.S. Food and Drug Administration (FDA), mostly involve inadequate record keeping, but they also include unapproved changes in experimental protocols. Animal activists who obtained the report claim that the irregularities raise questions about the integrity of trials involving potential new drugs and medical devices.

The Coulston Foundation, a private breeding and research facility in Alamogordo, New Mexico, conducts research into AIDS, spinal cord injury, and vaccine development. It has long been a target of animal rights groups, most recently when the Air Force transferred 111 chimps, many of them descendents of animals used in the space program, to the facility. In September, the foundation agreed to give up 300 of its 600 chimps after the U.S. Department of Agriculture charged the lab with animal welfare violations related to the deaths of five chimpanzees (Science, 10 September, p. 1649). Last month the Center for Captive Chimpanzee Care was awarded custody of 21 of the Air Force chimps.

The lab irregularities are described in a 31-page report by an FDA investigator, who lists alleged infractions without comment. The report, obtained by In Defense of Animals (IDA), based in Mill Valley, California, states that laboratory workers kept inadequate records of some animal conditions, changed experimental protocols without proper approval, and failed to collect necessary tissue and urine samples. In one case, according to the report, three animals in a study lost approximately 20% of their body weight in a matter of weeks and another died. Despite this, the report states, no animals were removed from the study for medical reasons. Another item notes that there was no documentation of physical and neurological exams required by an experiment. The report also found violations in record-keeping requirements, including data and observations recorded on loose “scrap paper,” and noted the use of “deteriorated or outdated reagents and solutions.”

IDA says that the document highlights sloppy science by Coulston, which receives much of its support from the National Institutes of Health but also tests new products for pharmaceutical and medical device companies. “It's far more than just record keeping,” says IDA's Eric Kleiman. “If a protocol calls for tissue samples to be taken and they're not, that could damage the whole study.”

Coulston Foundation spokesperson Don McKinney says the lab has responded to the report with “foundation-wide changes” in record-keeping procedures to comply with FDA requirements. He says he does not believe the infractions jeopardize the validity of the three studies covered by the inspection, but “we always take these things very seriously.” Coulston's top management, he says, met with quality-assurance and scientific staff to discuss the report.

James McCormack of the FDA's Bioresearch Monitoring Program declined to comment while the investigation is still active. However, in some other cases involving violations of good laboratory practices, the agency has ruled that affected studies could not be included in applications for drug or product approval. Punishments can range from a warning letter to disqualification of the facility. The agency is expected to issue a final report in a few months.

Other researchers who carry out clinical studies with primates say the report is likely to be a blow to the foundation even if it does not affect the results of specific studies. “Anytime FDA raises concerns … it's a pretty serious matter,” says virologist and immunologist Krishna Murthy of the Southwest Foundation for Biomedical Research in San Antonio, Texas, who has served as principal investigator on several primate studies subject to FDA approval. Bill Hobson, president of Sierra Biomedical in Sparks, Nevada, says he would be “surprised” if the research was compromised but that the report could have financial repercussions. “These things are open to the public, and our competitors use them” as ammunition when bidding for contracts, he says.

10. INTERNATIONAL COLLABORATION

# University of Cambridge to Team Up With MIT

1. Michael Hagmann

Cambridge, U.K.—When leaders of the Massachusetts Institute of Technology (MIT) gathered in their Cambridge, Massachusetts, offices to consider which top-notch European university might make the best partner for a broad research and education alliance, it is perhaps not surprising that they chose that other Cambridge, home to one of Europe's oldest and highest profile universities. And their choice may have been swayed by the fact that it's not going to cost them a dime. On Monday, Britain's Chancellor of the Exchequer Gordon Brown announced that the British government would invest more than $100 million over the next 5 years to help jump-start the new Cambridge-MIT Institute. Brown was the principal architect of the partnership and first approached MIT leaders about 18 months ago, having been deeply impressed by MIT's track record in converting science into successful businesses. “If you look at what MIT has achieved in its time, it is actually quite frightening,” a treasury spokesperson says, pointing at MIT's top ranking in patents awarded to U.S. universities and the more than 4000 companies it has spawned. MIT had been approached by several foreign institutions, but “the fit seemed to be best with the University of Cambridge,” says Lawrence Bacow, chancellor of MIT. The institute will not be built of bricks and mortar, but will make use of existing infrastructures. Staff and student exchanges, joint research and education projects, and adapting MIT's business programs to the United Kingdom are the main ingredients of the deal. The British government will provide about 80% of the total budget for the next 5 years through its Capital Modernization Fund, and private industry will chip in the rest. Despite Brown's focus on what Britain has to gain, MIT insists it is more than a hired gun. “We'll get a lot out of it as well,” says Bacow. “This relationship provides extraordinary resources [for MIT] and an opportunity to collaborate with the University of Cambridge in a lot of areas.” Cambridge Vice Chancellor Alec Broers agrees: “This ties together two prime research institutions from two different environments, and that's the way the world will have to go. If you want to be at the forefront of the scientific endeavor, you've got to have an international outlook.” International ties between universities are not new, but what makes this alliance unique is its broad scope. Unlike some more focused collaborations MIT has embarked on, such as a pending deal between MIT's Media Lab and the Irish government that would create a$200 million information technology teaching center in Dublin, “faculty from all our five schools will be engaged,” Bacow says. Whether the new institute delivers will be seen after the initial 5-year funding runs out, when spin-offs and licensing fees are expected to pay more of the bills. If everything goes as planned, Bacow expects a lot more Cambridge-to-Cambridge traffic by next spring.

11. SCIENTIFIC COMMUNITY

# Tenured Women Battle to Make It Less Lonely at the Top

1. Andrew Lawler*
1. Andrew Lawler is a Science staff writer and former Knight Science Journalism fellow at the Massachusetts Institute of Technology.

Senior scientists at MIT and Harvard find their voice amid growing discontent with their institutions' slow progress in hiring and retaining female researchers

“I thought how unpleasant it is to be locked out; and I thought how it is worse perhaps to be locked in.”

—Virginia Woolf, contemplating women in academia, in A Room of One's Own

Cambridge, Massachusetts—It took more than a year of fussing with tape measures, typing out a 13-centimeter stack of pleading memos, and haggling with her department chair, dean, and provost, but Nancy Hopkins finally won an additional 19 square meters of lab space to expand her promising work on the mutagenesis of zebrafish. It wasn't until a few months later, as she sat writing a grant proposal on a cold Saturday morning in early 1994, that the ignominy of the experience hit her.

“I suddenly realized my own insignificance, my lack of value” in the eyes of her colleagues, recalls the 56-year-old tenured molecular biologist at the Massachusetts Institute of Technology (MIT) here. She reran in her mind a long series of unpleasant incidents that had dogged her 26 years at the institute—from the big fight for a little lab space to an ongoing battle with male professors over ownership of an undergraduate course she had developed. And for the first time in her career, she felt that the common thread was gender—that she was of less account than her male colleagues and that her accomplishments were all but invisible in a primarily male world. “It was as if I didn't exist. It was a very strange sensation and very unpleasant. Fortunately, it turned to anger.”

The fruits of that anger landed Hopkins on a White House dais this past April, where she discussed gender inequities in her workplace as she sat between an admiring U.S. President Bill Clinton and his wife Hillary. Even more surprising was the astonishing public admission just weeks before by MIT President Charles Vest that the university had been guilty of systematically depriving distinguished women scientists like Hopkins of their fair share of salary, lab space, and other resources.

Hopkins's sudden celebrity coupled with MIT's admission and an accompanying report are part of a new groundswell of concern about the status of women professors in the sciences. A congressionally mandated committee is holding public hearings on the issue, a series of recent symposia have focused attention on the small number of female researchers, and faculty women and sympathetic male colleagues around the country are debating the matter more openly with administrators (Science, 11 June, p. 1757).

In contrast to the bitter affirmative action battles of the 1970s and '80s—marked by legislation and angry marches—the new challenge to university administrators is quieter but potentially more formidable, for it is being mounted by respected professors with tenure. They have chosen to spend their careers inside the academic enclave—and so are locked in, as Woolf put it—but now they find themselves frustrated by the glass ceiling that many male and female academics say still separates the sexes at universities. “We probably won't be as radical as [previous activists], since we want to work within the system rather than be confrontational,” says Cynthia Friend, the sole woman chemist on Harvard's faculty and co-founder of a new panel seeking to increase the number of women researchers at that university.

Their task is quite different and in some ways more difficult than that of their predecessors. Rather than confronting open opposition from institutions, they are struggling with subtle inequalities stemming from the unconscious attitudes of individuals. “But the people involved are not going to give up easily, and we're not going away,” says Friend. Adds Melissa Franklin, Harvard's first female tenured physicist, “It's up to us to force the issue.”

The numbers tell part of the story. After nearly 2 decades of struggle, resulting in considerable gains, women still make up only 12.5% of senior faculty (associate and full professors) in the natural sciences and engineering at all U.S. universities and 4-year colleges (see upper graph), according to National Science Foundation data. In the top 90 U.S. research universities in 1995, less than 10% of senior faculty in those disciplines were women. And at the very top of the academic heap, the numbers are particularly lopsided: In 1995 less than 5% of Harvard's senior faculty were female, and at the MIT campus just down the street, women made up only 6.2% of the top ranks.

Although the percentages of female junior faculty members in all of these categories are roughly double those of full professors—a promising trend—women remain a small minority on science and engineering faculties. And at some institutions, even though the national pool of young women scientists continues to expand (see lower graph), the numbers are moving down rather than up. At Harvard, for instance, the percentage of women junior faculty in the natural sciences dropped from 19.7% in 1995 to 13.7% this year.

The fact that women tend to leave the scientific track at much higher rates than men is well documented (Science, 29 March 1996, p. 1901). Now there is disturbing evidence that even the highly successful women who remain in academia and prosper may feel desperately unhappy and out of the loop with their colleagues. That unhappiness gets transmitted to younger women starting out and may help scare a new generation away from academia, many researchers warn. “I've talked to many female students who tell me, ‘I don't want to be like you’” because of the treatment of women, says MIT materials scientist Lorna Gibson. Other MIT and Harvard female professors repeat that story.

The situation may be most acute at leading institutions, where, for reasons that are under debate, senior women tend to be fewer and thus more isolated. A close look at women scientists at two of the nation's top universities, Harvard and MIT, reveals trends that likely affect women at most research universities, but are more acute and visible at these two elite schools. At MIT, the administration has admitted the problem and started on solutions, but most observers say that Harvard is only beginning to struggle more openly with this sensitive issue. And the way these top schools deal with the problem of women faculty inevitably will have national effects. “When an institution like MIT says, ‘Yes, we have a problem,’ it puts a lot of pressure on everyone else,” says Marc Kastner, chair of MIT's physics department.

Hopkins has clear evidence that the concerns she helped raise extend beyond Cambridge. Since spring she has received a flood of phone calls from women academics asking advice (see sidebar on p. 1278) as well as numerous invitations to speak on the topic around the country. “It's pretty clear this is a general problem,” she says.

## MIT's quiet revolution

Hopkins is an unlikely ringleader for women's rights. Her prim manner, conservative dress, and the slight English accent inherited from her mother are hardly evocative of an academic radical. “Feminism?” she asks. “I avoided it like the plague throughout my entire career. I just ran from it. I didn't have this problem; I thought it belonged to a previous generation.” Nobel Prize-winning biologist Barbara McClintock, who befriended Hopkins early in her career, tried to warn her. She said that in terms of discrimination, “to be a woman scientist is worse than to be black in America,” recalls Hopkins, who was aghast at the comparison. In a 1976 letter to her young colleague, McClintock noted that “successful competition with men is just out of the question … even when the woman is intellectually superior.” At the time, Hopkins thought the message too harsh. “I didn't want to hear it. I felt totally accepted.”

It wasn't until nearly 20 years later, secure in an MIT tenured professorship, that her first real doubts were sown as she struggled for the additional lab space. Then a course she had developed was taken over by other (male) professors, who wanted to commercialize it, and she stopped teaching entirely in protest. After her realization in January 1994, she decided to send a letter to Vest spelling out her mistreatment, and she asked a politically savvy female colleague to read it first. When that woman, whom Hopkins declines to name, asked to sign it as well, “I was completely dumbfounded. I wasn't alone anymore.” With trepidation, Hopkins and two other colleagues began to talk with the other 14 tenured MIT women scientists among a total science faculty of 280. “I was so embarrassed—these were very distinguished researchers, and I worried they would think I was one of those feminist types who just isn't good enough so I'm complaining,” says Hopkins.

The women had never before met as a group, but they quickly discovered common ground. Within weeks, all but one agreed there was a problem that required immediate action, and they scheduled an audience in August with Robert Birgeneau, dean of sciences. They spent hours discussing strategy and even held a dress rehearsal to ensure they got their points across succinctly. But they were nervous about their reception. “He could have brushed us off in a dean-like way, and that would have been it,” says Hopkins.

## Religious experience

Birgeneau, to their surprise, was ready to listen. A lanky 57-year-old physicist, father of three ambitious daughters and husband of a social worker, the dean calls himself “attuned to social issues.” One colleague credits his open-mindedness to his Canadian heritage. “Canadians do have a deep-rooted sense of fairness—it's deep in the culture,” Birgeneau adds. MIT was also facing other gender-related problems at the time, including a lawsuit by a former female engineering professor who was denied tenure (see sidebar on p. 1275), although Birgeneau was not involved.

To the dean, the meeting in his conference room that August day was “akin to a religious experience.” Each woman took a turn discussing her career at MIT, relating stories of condescension from male colleagues, a veil of invisibility that seemed to drape their accomplishments, and general frustration over benefits, resources, and administration support. The women agreed that the slights were typically not overt but rather stemmed from unconscious attitudes. Senior women simply did not get as much respect from their colleagues as senior men. “Death by a thousand pinpricks” is how one woman describes the experience.

The effect on Birgeneau, he recalls, was electrifying. “It was not possible to explain why the vast majority were extremely unhappy people” because of purely individual experiences, he says. “I became convinced that this was a systemic issue.” He agreed that the women could form a committee to gather data.

Hopkins says she and her colleagues “floated out of the office and danced down the street.” Soon after, however, Birgeneau appeared at Hopkins's office door with news of a snag: Department chairs were reluctant to admit that there was any kind of discrimination—conscious or unconscious—and strongly opposed creation of the committee. They feared that the panel could unnecessarily open a can of worms by digging for data on sensitive matters such as salary and lab space—typically confidential matters at a private university such as MIT.

But the effort went forward, thanks in large part to Birgeneau, who with the support of Vest brought the two sides together. Hopkins recalls an impasse at a 27 September 1994 meeting between the women and the seven male department heads in which six of the seven remained opposed. “They just sat there looking stony,” says Hopkins. But Birgeneau brokered a deal to add several distinguished male scientists to the committee, defusing the opposition, and the panel first met in February 1995.

The data that the group gathered over the next 3 years with the dean's assistance surprised even the tenured women. In one department, for example, they discovered that although both male and female junior faculty members had roughly 185 square meters of lab space, senior male faculty members had about 280 square meters, whereas their female counterparts had the same amount as their juniors, according to unpublished charts assembled by the committee. The number of university-granted awards within departments was often similarly skewed as well.

Perhaps the most shocking statistic was the most obvious: The total number of female faculty members in the sciences had not changed much since the days when McClintock had written to the young Hopkins. For more than 10 years, from the late 1970s to the mid-1990s, the figure had hovered around 20, out of about 280, or about 7.1%—a period during which the national pool of female science Ph.D.s grew steadily.

The committee also interviewed each woman professor in depth. They found that although junior women had relatively few complaints, tenured women felt marginalized and excluded from the workings of their departments. For example, several said they were excluded from search committees and encouraged to do more teaching than research. “The data part of the report has been overrated,” says Birgeneau. “The descriptive part is as important as the objective part. If these outstanding and high-achieving people—in the top 1% of women in the country by any measure—are miserable, that is a crucial kind of data point.” Much of the unhappiness, he says, originated in “daily insults—mostly unintended—and in obvious things like [space].”

Birgeneau didn't wait for a final report to move on the most obvious problems. “They started fixing things immediately,” Hopkins says. “Salaries, space, awards … they got right on it. It was a wonderful thing.” The dean also focused on building up the numbers of female faculty members: “I put a lot of pressure on the department heads to make sure they were working hard to find women candidates—and that has been very successful.” And indeed, since 1994, the number of women faculty in the school of science has grown more than 50%, from 22 to 34, as the number of men dropped from 252 to 222. The math department, for example, had no women, and now has four. Physics chair Kastner says that “it is absolutely necessary to change our attitudes,” adding that he and his colleagues “scour the landscape” for qualified female candidates and compete fiercely with other institutions to get them.

The report included an extensive rebuttal from male colleagues, who in several cases said that the negative statements were simply untrue. One MIT official denied a written statement by three of his female colleagues alleging a long-standing pattern of discriminatory behavior, according to sources familiar with the document. Despite the rebuttal, the administration clearly took the women's concerns seriously, and although the 150-page report was deemed confidential, a summary was made public last spring, generating an unprecedented wave of publicity for MIT. That publicity culminated in Hopkins's trip to the White House and the Clintons' praise of the university for doing the right thing—and for creating what they said should be “a model for the rest of higher education.”

MIT is now setting up similar committees in the other four schools—engineering, architecture, humanities and social sciences, and management. Each will examine teaching loads, search committee membership, and benefits, along with salaries, space, and award issues. “We want this effort to spread,” says Gibson, who leads the engineering school's women's committee. She says she feels that the administration is committed to doing so, although she worries that some areas, such as benefits—which many women say are out of step with the realities of two-career marriages and child care—require a more dramatic overhaul than MIT has been willing to consider. Gibson adds that the spotlight of publicity will help ensure continued change: “If they don't keep moving, they will look hypocritical.”

## Harvard women: Rarest of the rare

Just two subway stops away, Cynthia Friend says she has no complaints about salary, resources, or benefits. “I've been treated very well by the university,” says the Harvard chemist. But she and a handful of other female as well as male senior faculty members at the nation's oldest university echo the chief concerns of their MIT colleagues: too few women and too little respect and power for the few who are there.

Friend, a trim 45-year-old with more than 17 years of experience at Harvard, is wary of discussing matters that don't pertain to her number one priority, research. But after a busy day teaching class, working with graduate students, and writing grant proposals, she hesitantly confesses to an intense feeling of isolation in her tenured job. “I'm often excluded from informal meetings and interactions, where comments are made and decisions taken behind the scenes,” she says.

Friend is in fact quite isolated: She is the sole woman among Harvard's 21 chemistry faculty and one of only 10 tenured women, out of 156 tenured professors, in the natural sciences. One-third of Harvard's natural science departments have no senior women at all, and nearly half have no junior female faculty members. Even the two biology departments—where, for nearly a generation, half the graduate students have been women—have only seven women out of a total faculty of 55, or 12.7%. In other words, says Friend, Harvard lacks a critical mass of women in the sciences. “We can't do the kind of report MIT did,” she adds. “We don't have the numbers to do anything that is statistically meaningful.”

None of this particularly bothered her as a junior professor intent solely on research, says Friend, echoing the pattern laid out in the MIT report. It is only as a mature faculty member, trying to have an impact on the institution, whether in organizational issues, hiring, or student requirements, that she has become frustrated. “This isn't about quality of life; this is really about power, about respect from colleagues,” she says.

As a first step, Friend set out to change the statistics. She joined forces with John Dowling, a tenured microbiologist who has watched with concern for more than 25 years as talented female graduate students and postdocs left for jobs in publishing, teaching, and industry. The pair then signed on three other like-minded men and women, including computer scientist Barbara Grosz, who chaired a 1991 panel that concluded that Harvard was having “serious difficulties” attracting women to its science graduate programs and faculty. Their common goal: more female hires.

This past July, they gained an audience with Jeremy Knowles, the powerful dean of Harvard's arts and sciences faculty, in his elegant corner office overlooking Harvard Yard. The courteous 64-year-old chemist welcomed their initiative to encourage the hiring of more women scientists at both the junior and senior levels. Their plan is not to force more hires but rather to meet with department chairs to create a strategy for increasing the pool of women candidates in each discipline, starting with chemistry and the two biology departments. “It is absolutely essential that departments come up with plans to track and recruit women to join the faculty,” says Grosz. “Not a quota system, but a way to ensure that serious women candidates are being considered.”

The group has no formal power, but it does have the dean's imprimatur in the form of a 28 September letter urging cooperation, which was sent to the entire natural sciences faculty, as well as administrative support from his staff. The panel members, however, say they will not write an MIT-style report. “Our objective is action,” says Friend.

Knowles is under pressure from above as well as from below. The university's board of directors, called overseers, last spring urged Harvard President Neil Rudenstine in a confidential report to take specific steps as quickly as possible to increase the number of women faculty in all departments. Although Harvard officials declined to release the report, which was written for Rudenstine by an overseers' subcommittee, overseers say the message is clear. “The numbers are deplorable,” says Charlotte Armstrong, a New York management consultant and Harvard alumnus who chaired the subcommittee. “This has been a gnawing problem for too long, and something should be done,” particularly about the stagnant numbers of junior women faculty members. “And in science, the problems are more acute and require more attention,” she adds.

What's more, there is a perception among some leading outsiders that Harvard is out of step on the matter of women. “There is some feeling outside Harvard that it is not really serious about promoting women,” says Marye Ann Fox, chancellor at North Carolina State University in Raleigh. In Harvard's defense, Knowles notes that the number of tenured women on the natural sciences faculty has more than doubled—from four to 10—since he took the job in 1991, the same year MIT's Birgeneau became dean. “It's getting to be not such a small number,” he adds delicately. And he and other Harvard administrators also stress that many of the issues raised in the MIT report are not a problem at Harvard. For example, Knowles, not the department chairs, sets senior professor salaries, and junior salaries are on a scale; lab space is allocated not solely by department chairs but is subject to central control. Says Carol Thompson, Knowles's associate dean for academic affairs: “We don't have the same kinds of problems” as neighboring MIT.

## Poor pickings

All the same, the Friend panel confronts an organization entrenched in its traditions. Once someone receives Harvard tenure, for example, it is extremely rare for him or her to leave. “I can turn over the whole college in 4 years,” says Knowles, “but the tenured faculty takes more than 35.” That means fewer slots and many old men. Second, Harvard in the past has opted to bring in world-class scientists from outside and very rarely promoted junior faculty, “though the most successful tenured women [at Harvard] come from within the junior ranks,” says Joan Hutchins, a Los Angeles manufacturing executive and chair of the Harvard overseers. And Friend notes that “competition is high for senior women candidates, and they are often not as mobile.” Knowles notes that the tradition is changing: Today, nearly 40% of full professors came from within.

Perhaps the most intractable tradition is the mysterious process that transforms a junior professor into a member of the elite caste of tenured Harvard professors—a remarkably grueling procedure in which a panel of outside experts vets candidates. Each professor in the department writes a confidential letter to the committee, and ultimately the president makes the closely held decision. One male professor familiar with the process says it judges candidates on their merit. “We don't look at sex or ethnicity or other nonintellectual qualifications,” he says. “It's all what they published, their status, and how clear their thinking is.”

The reason there are so few tenured women, several department chairs say, is not discrimination but simply that there are so few qualified women candidates in most natural sciences. “The existing pool is just too male-dominated—there are not many women,” says Ramesh Narayan, who heads the 17-member astronomy department, which has two women—one of whom was tenured earlier this fall and one whose status is in dispute (see sidebar on p. 1277). “The pickings are just not very good,” adds another.

But that's not the way Friend and others see it. They note that the steadily growing pool of women candidates in all disciplines outpaces Harvard's hiring. And the tenure process “is an invitation to abuse,” says Howard Georgi, a Harvard physicist who has served on search committees and is a member of the new panel. “There's no question this has affected women.” The letter in particular allows faculty members to slight those candidates who may be different in any way, he says. “It is easier for someone who is exactly the same as everybody else on the faculty to get tenure.” Friend agrees, saying that “there's a tendency to use the reflecting pool method of hiring—which means you have a bunch of faculty who see themselves and that's who they hire.”

Her group argues that there are excellent qualified women out there—if one troubles to look for them. The panel therefore plans to work with the departments to find them. “We don't dig like we should,” says microbiologist Dowling. “We can't sit still. We need to be aggressive.” Department heads promise that they are open to the idea. “I don't know what more we can do, but we will listen to what they have to say,” says Narayan. And Hutchins says she hopes the new Radcliffe Institute—formerly the college for women—which plans to bring promising women scholars to the Harvard campus for a year, will provide a forum for showcasing top-notch women.

Ultimately, tracking progress and encouraging action falls to those at the top, and some are skeptical that hiring women is a priority at Harvard's most senior levels. “Saying this is a departmental issue is really passing the buck,” says one female former junior professor who left Harvard after not getting tenure. “There has to be a clear and specific directive at the level of the dean and the president.” Dudley Hirschbach, a Harvard chemist on the new panel, adds: “The attitude here is ‘Oh yes, we would like more women,’ but because no one is focused on this attitude, change is very slow.”

But, as at MIT, change is possible. Georgi describes the physics department in the 1980s as a male club that was “something out of an old English novel.” But while chair in the early 1990s, he made the issue of women a top priority, and junior professor Melissa Franklin became the first tenured woman in physics. Since then, two more women have joined the senior ranks. Did he meet resistance? “Resistance is the wrong word—it was more bemusement and lack of understanding,” he says.

Despite the relatively progressive atmosphere among Harvard physicists, however, Franklin says “this is not the nicest place to be an old woman. People are still condescending. They can be pretty rude.” She recalls, for example, being asked in a departmental meeting to speak more quietly. “It was as if I was being told to be somebody else,” she says. How does she cope? “You move a little way out of the action; you do your own thing,” she says. “And sometimes I go into my secretary's office and cry.”

## Fairy-tale ending?

The winds of discontent at MIT and Harvard appear to be spreading south and west. When MIT physicist and Harvard overseer Mildred Dresselhaus visited the University of Texas, Austin, in September to discuss research matters, she was ushered into an auditorium of 250 people eager to hear about the MIT report and her experiences as a woman scientist. The next morning, a dozen female postdocs bombarded her with questions at breakfast. “This is a front-page item,” she says. “There's a lot going on.” Hopkins reports similar reactions during her visits to universities ranging from the California Institute of Technology in Pasadena to the University of Vermont, Burlington, to discuss gender issues. “The universality of [those issues] is completely astounding,” she says. Although eager to return to full-time research, Hopkins adds that she feels obliged to respond to the barrage of interest in the subject. “It's awkward, but how can I avoid it?” she asks.

Meanwhile, the congressionally chartered Commission on the Advancement of Women and Minorities in Science, Engineering, and Technology Development is holding public hearings (the next will be held 7 December at the National Institutes of Health in Bethesda, Maryland) and is formulating a report on specific strategies for how to deal with the slow pace of change in academia as well as business and government. Hopkins advocates radical action by the commission—even recommending that federal research dollars go to easing the struggles of women scientists through child-care funding, for example.

She and others maintain that universities and science as a whole will be the ultimate beneficiaries of the push to boost the numbers and improve the lot of women researchers in academia. “This is not a women's issue—this is a university issue,” says Harvard's Grosz. “If we are not getting the best women, we are not getting the best people. We are supposed to be the best university in the world, so we ought to have the best women. Why don't we?”

Improving the lives of female professors will also likely have a long-lasting effect on the career choices of the next generation, advocates say. If role models feel marginalized, female students are likely to opt out of academia. “Doing the MIT study turned out to be a very good investment in terms of increased productivity and quality of life for the faculty,” says Dresselhaus. “But the biggest impact is on graduate students and even undergraduates who view careers in academia as undesirable.”

Certainly students encountering Hopkins today will get a different picture of life in academia than those who met her 5 years ago. Although she still worries that recent gains are fragile, her research is blossoming, she was recently named a member of the National Academy of Sciences' Institute of Medicine, and the change in attitude toward women at MIT has in turn transformed her own attitude. “I used to be so unhappy much of the time,” she says, bustling out of her cluttered office in a white coat and down the hall to the lab where her zebrafish swim. “Learning how to access the resources of MIT, my own life has become a fairy tale. I feel incredibly lucky to be here now.”

12. SCIENTIFIC COMMUNITY

# MIT as 'Intractable Enemy'

1. Andrew Lawler

Today women from Hillary Clinton on down are praising the Massachusetts Institute of Technology (MIT) for recognizing and beginning to correct its unfair treatment of female scientists (see main text). But 5 years ago, at least one woman viewed the prestigious school not as an ally but as a powerful enemy. In 1994, the same year that senior biologist Nancy Hopkins and her colleagues were taking grievances to their superiors and finding a compassionate ear in the school of science, the MIT administration was fighting a messy sex discrimination suit involving the school of engineering. The suit was filed by Gretchen Kalonji, an associate professor in the materials science and engineering department, who specializes in crystalline defects and their effects on the physical properties of materials. With a bachelor of science degree and a Ph.D. from MIT, she was the second woman to be hired by the department. By 1986 she was an associate professor on the tenure track. “The situation was grave for junior women,” several of whom did not get tenure, she recalls.

Kalonji herself was turned down for tenure in 1988. Arguing that she was qualified for tenure and had been discriminated against because she was female, she appealed to the dean of the school of engineering, who organized a committee to examine the matter. That group found that the tenure process was “unacceptably flawed,” according to the committee's confidential report, which was presented to the dean and obtained by Science. The investigators determined that the department “was less supportive of women” and that Kalonji faced “a higher hurdle than some males.” In addition, “senior male members of the department stereotype women, making the atmosphere inherently more difficult for women.”

Kalonji's lawyer, Michael Altman of Boston, says that faculty members on the tenure committee who were interviewed as part of the investigation noted that “people talked about the fact that she was married to an African and was politically left.” Kalonji adds that she was actively pressing for university divestiture of its holdings in South Africa because of that country's apartheid policies, and that this had created tension between her and her colleagues and superiors.

The dean organized a second committee to reevaluate the tenure panel's decision. According to Kalonji, he ordered members not to consider the disadvantages Kalonji may have faced as a result of discrimination, but only her credentials. The committee denied her tenure again, and in 1991 the dean confirmed that decision. By then, Kalonji had moved to a position at the University of Washington, Seattle, where she has tenure today.

After 3 years of fruitless waiting for a backlogged Massachusetts state office to consider her complaint, Kalonji instead filed suit in federal court in 1994. She argued that her research support had been minimal, that she had been granted far less lab space than her male colleagues, and that she had been pushed into working on a defense contract that impeded more prestigious research. All of those disadvantages affected her tenure bid, she maintained.

The university strongly denied that any discrimination had occurred. One MIT official familiar with the suit says Kalonji made a persuasive case, but another university source recalls that there was a general feeling in the engineering school that she lacked the qualifications for tenure. The university fought hard to prove that point. “MIT proved the most intractable of enemies,” says another university official. At the eleventh hour, just as the dispute was to go before a judge in 1995, MIT agreed to settle for an undisclosed amount. Kalonji received the last of a series of payments in January, and, at her insistence, MIT also agreed to spend at least \$50,000 a year for 5 years on a national program encouraging women and minority grad students and postdocs to move onto university faculties. Kalonji initially chaired the effort but has since relinquished the position, and she says that the program appears to have languished.

A joint 1995 statement by Kalonji and then-MIT Provost Mark Wrighton, now chancellor at Washington University in St. Louis, announced the new program as a “key element” in her withdrawal of the suit. Wrighton did not return phone calls, but current MIT officials say the welcome granted to disgruntled women in the school of science that same year was not connected to the diversity initiative or to Kalonji's suit. But Kalonji feels that “the suit had a positive effect. The fact that they were forced to settle with me woke up the administration.”

13. SCIENTIFIC COMMUNITY

# Margaret Geller: Battling Discrimination or Bureaucracy?

1. Andrew Lawler

One morning in mid-May 1997, astronomer Margaret Geller received a letter from Jeremy Knowles, dean of Harvard University's faculty of arts and sciences, offering her a Mallinckrodt chair at Harvard—an honor traditionally reserved for outstanding tenured scholars at the university. Geller, a researcher at the Harvard-Smithsonian Center for Astrophysics, was euphoric, and she rushed out of her office to tell one of her graduate students the good news. But when she learned that Harvard tenure did not come with the chair, her euphoria turned to fury.

Two years later, Geller still has not accepted the chair, and she and Harvard remain locked in an increasingly acrimonious battle over her status. Geller argues that her lack of tenure is a result of ill-concealed sex discrimination, the latest attempt by Harvard to deprive a distinguished woman scientist of its powerful stamp of approval and support. But university administrators say gender has nothing to do with the matter. They argue that bureaucratic reality—which also prevents Geller's male colleagues at the Harvard-Smithsonian center from receiving tenure—is the true stumbling block, which they are working in good faith to remove.

University officials do not question her credentials. Geller, 51 years old, the second woman to receive a physics Ph.D. at Princeton, is a member of the National Academy of Sciences and recipient of a coveted MacArthur fellowship, or “genius grant.” Her work plotting the distribution of galaxies with John Huchra, also a Harvard-Smithsonian professor, showed that matter hugs the edges of enormous voids and has an organized rather than a random pattern. (Ironically, the initial organized pattern was dubbed the Harvard Stick Man.) “She's quite a distinguished researcher with a lot of respect in the community,” says Princeton astronomer Ed Turner.

Geller was a budding junior faculty member at Harvard during the early 1980s. Then in 1986, before she came up for tenure, she resigned and moved to the Smithsonian side of the center. Although she declines to discuss why she left, colleagues say Geller felt the sting of discrimination as a female Harvard professor and was devastated when senior professors ridiculed her, saying that as a woman “she didn't have a snowball's chance in hell at getting Harvard tenure.”

She is now subject to the complex rules governing the joint Harvard-Smithsonian Center, down the street from Harvard's Cambridge campus. As a Smithsonian employee, she does not have Harvard tenure, even though she and her half-dozen male colleagues have already successfully passed through the difficult Harvard tenure process, which made them senior members of the Harvard astronomy faculty. They are Smithsonian civil servants, although some, like Geller and her colleague Huchra, receive an additional partial salary from Harvard (25% in Geller's case). But should Smithsonian funding dry up, Harvard is under no commitment to pick up their full salaries.

This rankles Geller, who teaches a full course at Harvard each semester, mentors graduate students, and until recently spoke frequently at Harvard alumni and fund-raising events, often winning praise from university administrators, including a congratulatory letter from Knowles. “I have a commitment to Harvard, but Harvard does not have a commitment to me,” she says. Geller also notes that Harvard's past credentials with regard to promoting women are less than stellar. For example, earlier this century, when other schools had tenured women on their faculties, Harvard dallied for decades before awarding tenure to such renowned scientists as variable star expert Cecilia Payne-Gaposchkin and biologist Ruth Turner. Today, Geller is also angered that Harvard counts her as tenured faculty on its lists, boosting the apparent numbers of tenured women.

A Harvard official acknowledges that Geller's strange status creates “a sense of second-class citizenship” but adds that Smithsonian professors also receive benefits that their Harvard colleagues do not get, such as 12-month salaries and federal benefits. “Margaret is in the same position as six other [distinguished professors],” says Irwin Shapiro, center director. “Three are members of the National Academy, and most have won prizes.” Adds a Harvard official: “We felt we couldn't single out Margaret.”

The offer of a Mallinckrodt chair, however, did single Geller out, as her colleagues did not receive this honor. After the written offer in May, however, Knowles sent Geller a letter on 16 June citing her “scholarly eminence and distinction” but noting that there would be no impact “on [her] economic or contractual relationships.” Geller was incensed. “I decided not to live the lie of this professorial title,” she says, and she has yet to decline or accept the offer, leaving the proffered chair in limbo.

Knowles declines to discuss the matter, but university and Smithsonian sources say that the offer of a chair was an attempt to placate Geller that clearly backfired. “The university is afraid that if they tenure her, the rest of [the Smithsonian faculty] will get pissed off and leave,” says one source. “We'd have six other people in line,” adds another official. And one colleague complains: “She's treated with kid gloves. She's already made herself first among equals. It's not fair that she alone gets tenure.”

Officials from both institutions are now working on a plan to grant all the Smithsonian professors Harvard tenure with a financial commitment by the university. That outrages Geller, who says that an en masse tenureship diminishes the honor. “I'm worth that many men?” she quips. She says that “[Harvard astronomy chair Ramesh] Narayan and Shapiro used my situation to push forward a plan to tenure all Smithsonian professors regardless of stature.” Both men reject that idea. “We've been trying to win equity for years,” says Shapiro. “There is no gender component to this story,” adds Narayan.

Members of a fledgling panel organized to help increase the numbers of women in the sciences at Harvard (see main text) declined to comment on Geller's situation, saying they do not know enough about the particulars. But the astronomer attracts plenty of off-the-record carping at Harvard. One male academic describes Geller as having “a bee in her bonnet.” And a colleague sympathetic to her plight says, “She has a confrontational style that magnifies the problem.” To Geller such criticism is, if anything, more evidence that gender is indeed part of her problem, because women fighting discrimination traditionally have been dismissed as difficult or confrontational. “A lot of women are called such names when they stand up for what they merit, while a man would just be called aggressive,” she says. Her effort, she adds, has stopped short of legal action but has cost her enormous mental distress and hurt her health. “These men,” she fumes, “can't imagine having something like this happen to them.”

14. SCIENTIFIC COMMUNITY

# From MIT, a Primer on Boosting Women's Status

1. Andrew Lawler

For researchers eager to improve the position of women at their own institutions, scientists from the Massachusetts Institute of Technology (MIT) offer some hard-won advice.

• Start From Grass Roots: An edict from above is not enough. “Women have to organize themselves,” says Robert Birgeneau, dean of sciences at MIT. Such organization puts pressure on the administration to act.

• Safety in Numbers: The great lesson for Nancy Hopkins, the biologist who kicked off the MIT effort, is the power of solidarity. “Depend on the power of the group, because it works,” she says. “If you all go to the administration, they can't say there's no problem.” That means first building trust with one another, adds MIT biologist and engineer Penny Chisholm. “Suspend suspicions among yourselves, overlook cultural and departmental differences, and get to the common experiences.”

• Find an Administrative Ally: “You have to have a Dean Birgeneau,” says Hopkins, lest the effort languish in the university bureaucracy. MIT's dean of science was the hero of the MIT saga, according to many women involved. He took their claims seriously, gained the support of MIT's president, and worked tirelessly to forge innovative compromises.

• Include Men: “It's very important to have well-respected male faculty on board,” says Birgeneau. They add credibility, defuse tensions, and can help win over male colleagues. “At first I was against [including men],” says Hopkins, “but the dean turned out to be absolutely correct.”

• Collect Data, Not Enemies: “A spirit of cooperation works better than confrontation,” says Birgeneau. Gathering data and quietly discussing it was more effective than loud protests, say some MIT faculty members. And data gathered internally are likely to be more valuable than those produced by outside consultants, who may have a hard time penetrating departmental cultures, says Hopkins.

• Get the Resources: Hopkins skipped teaching for 2 years while she spent 30 to 40 hours a week gathering data and conducting interviews. “The institution has to say this is important enough to give you relief from teaching,” she says. And Birgeneau says if he had to do it over again, he would hire a full-time assistant to help.

• Seek Out Personal Stories: Some science faculties, such as that of Harvard University, have too few women to make statistical analysis meaningful, but individual interviews can provide important insights, too. Allowing women to speak confidentially helps ease fears of retribution, Hopkins adds.

She says that an organized, visible effort is far more effective than fighting individual battles. “Changing hearts and minds one by one is much too slow,” she says. “You have to change the institution, and the hearts and minds will follow.”

15. GEOLOGICAL SOCIETY OF AMERICA MEETING

# Geology Near, Far, and Long Ago

1. Richard A. Kerr

Denver, Colorado—Late last month, geologists and paleontologists gathered for the annual meeting of the Geological Society of America, which is headquartered here in the central part of the continent. Topics wandered out to an asteroid of uncertain parentage and back in time to geologic clocks and the death of the dinosaurs.

## Measure for Measure in The March of Time

When your wristwatch and a wall clock disagree about the time, one (or both) of them is wrong. Geochronologists have a similar problem, but the potential consequences are more grave. In the limestone pinnacles of northern Italy's Dolomite mountains, a technique that marks time by counting sedimentary layers much the way tree rings are counted gives one answer for how long it took the rocks to form roughly 240 million years ago in the Triassic period. The uranium-lead radiometric technique—a pillar of geochronology—gives a very different answer.

“There's going to be a lot of work figuring out how much time is involved,” says sedimentologist Bruce Wilkinson of the University of Michigan, Ann Arbor. Geologists and paleontologists are anxious to know which method they can trust to gauge the pace of evolution's Cambrian explosion, say, or the timing of huge volcanic eruptions relative to mass extinctions that they may have triggered.

Time is made visible, and perhaps even measured out, in the majestic Latemar limestones of the Dolomites. These rocks are a 600-meter-high pile of carbonate skeletons of marine animals laid down layer by layer on an ancient ocean floor. It all took 8 million years, sedimentologist Linda Hinnov of The Johns Hopkins University calculated by counting the meter-thick layers and making one crucial assumption: The clocklike orbital behavior of the planet controlled their deposition.

Astronomers know that Earth's tilt, the direction of its axis, and the shape of its orbit vary with periods of 20,000, 40,000, and 100,000 years, respectively, under the gravitational influence of other solar system bodies. During the past few millions of years, these orbital or Milankovitch cycles have driven climate changes and probably even set the pace for the comings and goings of the ice ages, leaving vivid records in deep-sea sediments. Like many other researchers trying to measure time in ancient sedimentary rocks, which generally can't be dated by radioactive decay, Hinnov assumed that the cycles had similar effects at earlier times in Earth history. So she looked for the fingerprint of the cycles in the pattern of the layers in the Dolomite limestones.

In the Latemar sequence, for example, the layers seem to form bundles of five, with a thick layer at the bottom of each bundle and the four above it progressively thinning. In the 1980s, researchers theorized that, if orbital cycles somehow varied the productivity of the carbonate-yielding marine animals, each layer could be the product of 20,000 years of sedimentation under the influence of one cycle in Earth's axial orientation. The bundles of five would form the 100,000-year cycle; later work seemed to identify the 40,000-year cycle as well in the layered rock.

At the meeting, however, geochronologist Roland Mundil of the Berkeley Geochronology Center in Berkeley, California, and his colleagues presented evidence that the Latemar layers have nothing to do with orbital cycles. Using the radioactive decay of uranium-238 to lead-206, they dated two thin layers of volcanic ash sandwiched in the limestone, separated by 420 supposedly 20,000-year layers. If orbital cycles really had ticked off the limestone layers like a clock, the dated interval should amount to 8.4 million years; Mundil measured an age difference of only 2.1 million years between the ash layers. Even under the most generous assumptions, says Mundil, “you would never get the time span you need for Milankovitch.”

Determining which clock is right will take some more work. The orbital method “is a very seductive hypothesis,” says paleontologist Paul Olsen of the Lamont-Doherty Earth Observatory in Palisades, New York, who has used it to date other Triassic beds. “Sometimes the criteria for recognizing Milankovitch [cycles] are so loose you can see it anywhere.” Yet the uranium-lead method has its difficulties as well. “The more you dig into the method,” says Olsen, “the clearer it becomes that getting dependable results is not a trivial matter.”

For example, rock containing zircon crystals that hold the uranium and its decay product can partially melt, millions of years after their formation in a volcanic eruption, in a new volcanic outpouring. The zircon can survive the melting and then grow a new layer of crystal over its old core. When the whole crystal is analyzed, the apparent age will be older than the age of the eruption that laid down the ash layer. Some geochronologists, including Mundil, say they address such problems in their standard methods, screening out zircons with old cores through inspection under the microscope. But others aren't so sure. They look to other techniques that can pick out chemically distinct cores that would otherwise be invisible. Telling which clock, if any, is right will obviously take more effort than dialing up the time lady.

## Vesta Family Shunning Asteroid Braille

Just who was that masked asteroid? Early last August, 5 days after the Deep Space 1 spacecraft flew by the 2-kilometer chunk of rock called Braille, team members thought they knew. They hailed an “astonishing, exciting, and surprising result”—Braille's “color” in the infrared gave it “a very high probability” of being a chip off the 500-kilometer asteroid Vesta (Science, 13 August, p. 993). The kinship, they said, supported the idea that Vesta had suffered a catastrophic collision that blasted debris into space, including Braille and the rock that occasionally falls to Earth as an unusual kind of meteorite.

Now, with more time to reflect, planetary scientists are calling Braille's paternity into doubt again. Team member Daniel Britt of the University of Tennessee, Knoxville, says Braille “is looking more like an ordinary chondrite”—another, more common meteorite type. That's an exciting possibility, too, because astronomers have only been able to track down a few asteroids capable of supplying Earth with these meteorites.

The initial identification had seemed solid; after all, Deep Space 1 had inspected Braille at crucial infrared wavelengths from just 10 or 15 kilometers away. Braille's distinctive pattern of absorption in the infrared, Britt told Science at the time, “absolutely nails it as a vestoid”—one of a class of asteroids whose colors suggest a dark, basaltic rock. Besides resembling Vesta itself, these asteroids also resemble the colors of a small class of meteorites called eucrites. The tints have convinced many planetary scientists that vestoids and eucrites are former bits of Vesta, presumably blasted off by impacts. “The Vesta connection [for Braille] looked pretty firm right after the flyby,” Britt says, “but now it looks less firm. I doubt it's [Vesta-like], but I don't want to rule it out. It will be a while until we're certain what this thing is.”

The uncertainty arises because astronomers aren't yet fully familiar with the quirks of the spacecraft's infrared spectrometer. To identify a specific mineral composition, and therefore a particular asteroid type, scientists must make precise measurements of how much infrared light is absorbed at particular wavelengths. But variations in the operating conditions of the instrument, such as temperature, can affect the readings. For the highest precision, team members wanted to calibrate the spectrometer thoroughly after launch by targeting a number of objects with known spectra, such as certain stars or planets. Unfortunately, says Britt, “we just didn't have many opportunities before the encounter.” Deep Space 1 is dedicated to testing new space-faring technologies such as its ion-drive engine, he notes, pinching the time available for science.

If Braille does turn out to be no relation to Vesta after all, astronomer Richard Binzel of the Massachusetts Institute of Technology won't be surprised. Before the encounter, he and his colleagues had concluded from ground-based observations at visible wavelengths that Braille most resembled ordinary chondrites, the most common meteorite and the rock type Britt is now leaning toward. If Braille continues to look like an ordinary chondrite, he says, it will join the growing clan of small, near-Earth asteroids that qualify as sources of 80% of Earth's meteorites (Science, 13 August, p. 1002)—not a bad bunch to have as relations.

## Dinosaurs Went Out With Bang, Say Bones

That big rock bearing down on Tyrannosaurus rex has become a standard image of dinosaur Armageddon for the public, but not for paleontologists. Although most of them now accept that a huge meteorite crashed to Earth 65 million years ago, many have been reluctant to believe that it killed off their favorite critters in one blow. Instead, they argue, dinosaurs were already gone or in decline before the impact; the meteorite was a mere coup de grâce. But at the meeting, two independent groups of paleontologists said that collections from the fossil fields of Montana and the Dakotas—perhaps the most thorough and systematic surveys of the last days of the dinosaurs—showed that these creatures were doing just fine until that big rock came by.

Both studies made use of volunteer field workers for the hard, sweaty summer labor of hunting up fossils in the badlands. Dean Pearson is himself a volunteer and an amateur, working out of the Pioneer Trails Regional Museum in Bowman, North Dakota. In 1983, at first alone and then with fellow amateur Terry Schaefer of the museum as well as professional paleontologists, he began collecting vertebrate fossils along the Hell Creek Formation, a 60-kilometer-long exposure in southwestern North Dakota and northwestern South Dakota.

The team eventually found and identified 10,034 vertebrate fossils scattered across the 100-meter height of Hell Creek sediments, which were laid down in the last 3 million years or so of the 160-million-year dinosaur age. Most of the taxa that they turned up—dinosaurs, fish, amphibians, lizards, turtles, crocodilians, birds, and mammals, among others—persisted throughout the Hell Creek sediments, said Pearson, suggesting that vertebrates as a group and dinosaurs in particular were not in decline. And the youngest dinosaur fossil found, a possible Triceratops, was just 1.8 meters below the thin layer of impact debris.

The pattern “is not compatible with a gradual vertebrate extinction,” Pearson says. Paleontologist Peter Sheehan of the Milwaukee Public Museum and his colleagues reached the same conclusion from a volunteer-aided dinosaur fossil survey in the more northern exposure of the Hell Creek. In their latest analysis of the bones of at least 984 dinosaurs, they, too, found no sign of a gradual extinction; their survey turned up as many fossils in the last 3 meters of the formation as in most other 3-meter intervals throughout the Hell Creek.

Pearson's study is “the first that shows there's no trend” across the Hell Creek and therefore no decline, says vertebrate paleontologist David Archibald of San Diego State University, who has argued in the past for a gradual extinction of vertebrates. But he doesn't think the Hell Creek studies are enough to settle the question. “There's no statistical basis at this point to say whether [the dinosaur extinction] was rapid or slow,” he says. Pearson found no fossils of any sort in the last 1.8 meters of the Hell Creek, laid down over some tens of thousands of years, he points out—not even fossils of taxa known to have survived the impact. Apparently bones simply did not get preserved during that interval, leading Archibald to conclude that the fossil record isn't good enough to say what happened.

Pearson and Sheehan are more sanguine. The dinosaurs had been around for a good 160 million years, Sheehan notes, and such hefty meteorites fall only every 100 million years on average. What are the chances that the great beasts died off just tens of thousands of years before the impact? “That probably didn't happen,” he concludes.

16. CHEMISTRY

# Does Life's Handedness Come From Within?

1. Robert F. Service

New results suggest that the weak nuclear force may be the source of the left-right bias of amino acids and other biomolecules

Richmond, Virginia—Even for molecules, life isn't evenhanded. Molecules that are essential to life, such as amino acids and sugars, can come in two mirror-image versions, like a left and right hand. Yet biology views these near twins as Cain and Abel, embracing one while shunning the other. Left-handed amino acids are the building blocks of all proteins and thus serve as the cornerstone of life. Their right-handed brethren, meanwhile, just don't fit into the scheme of things.

Researchers have been struggling for decades to explain how life acquired this bias, without success. But at the International Symposium on Cluster and Nanostructure Interfaces meeting here 2 weeks ago, a team of researchers from the United States and New Zealand reported preliminary results indicating that its source might lie in the heart of molecules themselves—in the so-called weak force that operates within the nuclei of atoms. If the new work holds up, “it will have a tremendous impact on science,” says Puru Jena, a physicist at Virginia Commonwealth University in Richmond.

Over recent decades, researchers have ranged far and wide looking for a phenomenon—astronomical, electromagnetic, or nuclear—that could have imprinted this handedness, or chirality, on nature. “It's really an open problem that people have looked at since the 1950s,” says Joshua Jortner, a chemist at Tel Aviv University in Israel. Perhaps the most popular recent contender has been rays of circularly polarized light from supernovae, for example. These light waves fly in a corkscrew fashion, spinning either clockwise or counterclockwise as they go. And researchers have shown that such light can skew chemical reactions toward producing one particular chiral molecule at the expense of its twin. But supernovae and other astronomical sources would generate both the left and right spinning forms equally and so would be unlikely to produce an imbalance in organic molecules.

Another candidate, the weak nuclear force, has seemed to be a long shot. The weak force governs the radioactive decay of a neutron in the nucleus of an atom into a proton and an electron, and the force has a handedness: The decay always produces an electron with a left-handed spin. Because the weak nuclear force is the only chiral fundamental force in nature, it was tempting to link it to the handedness of biomolecules. “But it's like a phantom,” says Jortner. “There has really been no evidence, because the effect is so weak.”

Chemical physicist Robert Compton and organic chemist Richard Pagni of the University of Tennessee, Knoxville, along with other researchers at UT, Oak Ridge National Laboratory, Berea College in Kentucky, and the University of Canterbury in Christchurch, New Zealand, set about trying to find some evidence. They turned to a type of salt called sodium chlorate, which forms chiral crystals, normally yielding left- and right-handed ones in equal numbers. These crystals contain arrangements of atoms that spiral either clockwise or counterclockwise through the crystals. Environmental factors can influence the direction of those spirals, however: If a solution of sodium chlorate is stirred, the crystals it produces will all be of one chiral type.

Compton and his colleagues wondered if lefty electrons produced by radioactive decay could produce the same effect. They weren't disappointed. When the researchers bombarded a solution of sodium chlorate with left-spinning electrons—from a source of radioactive strontium—they wound up with an excess of right-handed crystals. And when they hit the solution with positrons—positively charged counterparts to electrons, which have the opposite spin—an excess of left-handed crystals formed.

“It's a very, very interesting experiment,” says Roger Hegstrom, a chemist at Wake Forest University in Winston-Salem, North Carolina. But puzzling as well: Hegstrom's calculations—which only look at the effect of the lefty electrons—show that beta decay electrons should alter the crystallization of only about 1 out of 1 million experiments. Yet in Compton's experiment, “every single batch went in the same direction. That's quite significant” and can't be explained by current theory, Hegstrom says. But Compton points out that as the electrons hit the salt solution, they give off left-handed circularly polarized light, which can increase the chiral selectivity.

Still, Compton is quick to note other questions as well: “Whether this [process] is involved in the generation of chirality in amino acids is pure speculation.” However, he notes, electrons produced by radioactive decay are ubiquitous in the natural world, whereas the positrons that would cancel out their handedness are not. And that difference could have set the ball of prebiotic chemistry rolling toward a handed bias.

The group also went on to show another way the weak nuclear force might have tipped chemistry toward a particular handedness. In the sometimes quizzical world of quantum mechanics, electrons not only orbit the nuclei of atoms but sometimes actually pass right through the center in a process called tunneling. As they tunnel through the nuclei, these electrons encounter the weak nuclear force, which can alter their energy content slightly. And because chiral pairs start with slightly different electronic structures, their electrons tunnel with different spins. In theory, the nuclear encounters should alter electrons' overall energy, by as much as 1 part in 1 trillion.

This subtle difference is easiest to see in heavy atoms, so the researchers synthesized a pair of propeller-shaped chiral molecules with heavy iron atoms at their core. They then turned to a sensitive detection technique called Mössbauer spectroscopy, which fires a steady stream of photons—all of which carry the same amount of energy—at target molecules. If those incoming photons have just the right amount of energy, they are absorbed by the propeller's iron atom, which then kicks out a less energetic photon that is detected. The researchers found that the opposite-shaped propellers absorbed photons of slightly different energies, suggesting that the weak nuclear force in their cores had altered the iron's energy levels.

Compton says his team's experimental results are in line with theory. According to calculations, “the presence of the chiral electroweak force produces a shift in the energy levels of chiral molecules very close to this number that we're getting,” he says. Still, he adds, the work is preliminary, and his team has yet to do essential experiments to rule out possible artifacts.

Could such an energy difference have an impact on the origin of biomolecules? Possibly, says Compton. Other calculations show that the same effect would give left-handed amino acids a slightly lower overall energy than their right-handed brethren, which would favor their chemical production. But because the difference is so small, and thus the preference for the left-handed amino acids so weak, Compton believes that at this stage it's more likely that the spinning electrons given off by radioactive decay are responsible for biology's choice of handedness. If so, researchers may have finally found the source of nature's chiral bias: not light from the depths of space, but subtle forces in the very heart of matter.

17. ECONOMIC DEVELOPMENT

# A Shifting Equation Links Modern Farming and Forests

1. Laura Helmuth

New studies of deforestation around the world suggest that high-tech agriculture can be either culprit or savior

New research is raising questions about sustainable growth, a notion dear to both environmentalists and development specialists. Both camps have embraced the assumption that improving agricultural practices in the developing world should relieve pressure to cut down nearby forests. But when looking at more than two dozen cases of deforestation, economists David Kaimowitz and Arild Angelsen of the Center for International Forestry Research (CIFOR) in Bogor, Indonesia, noticed that the real-world equation was a bit more muddled: In Brazil, for example, a new strain of soybeans planted by farmers wound up accelerating the destruction of the tropical forest, while in the Philippines an irrigation project protected a tropical forest elsewhere on the same island.

In a book about their findings, due out next year, the duo also looks beyond these case studies to determine why agricultural development can have such differing impacts. Among the key factors they identify are how the new technologies affect the labor market and migration, whether the crops are sold locally or globally, and how profitable farming is at the boundary between cultivated land and forest. Senior environmental adviser John Spears of the World Bank calls the work “extraordinarily valuable” and says the bank is developing forest protection policies that take it into account.

Before the mid-1980s, says economist Robert Faris of the Harvard Institute for International Development, conservationists tended to be antigrowth. More recent thinking, crystallized in a 1992 world development report from the World Bank, suggested that economic development and environmental conservation could be complementary: As farmers earned more from their existing plots—thanks to better irrigation, new crops, an investment in tools, and easier access to markets—they would be less motivated to clear marginal land.

But when Kaimowitz and Angelsen examined studies presented at a CIFOR-sponsored conference last March in Costa Rica, they found that growth and conservation are only sometimes compatible. “If you think from the outset that the objectives [of development and conservation] are complementary, then you'll likely get it wrong,” says Angelsen.

One important variable is how much labor an agricultural system requires, says Angelsen, now at the Agriculture University of Norway in Aas. Brazilian soybean cultivation is highly mechanized, says Kaimowitz, and large plantations of a new strain that thrives in the tropics displaced small southern Brazilian farmers who had cultivated grains, vegetables, and coffee. These farmers were forced to the agricultural frontier, where they cleared forest to eke out a living.

In contrast, projects that create employment can relieve deforestation pressure, as a project on the Philippine island of Palawan shows, says economist Gerald Shively of Purdue University in West Lafayette, Indiana. An irrigation project there, he found, drew wage laborers to newly created rice fields in the lowlands and reduced pressure to cultivate forested areas. “You've got to create opportunities elsewhere to pull people away from the forest,” says Shively. Or even from farming itself: “As bad as it sounds,” says Faris, “sweatshops are friends of the forest” by concentrating laborers in already developed areas. “The question is,” he says, “what [forest] do you have left when you get to that point?”

Development theorists have also assumed that easier access to markets would make farmers' crops more profitable and thus allow them to farm less land and spare the forest, according to Kaimowitz. “But if you can produce twice as much, it makes just as much sense to produce more on more land,” he says. As an example, he points to Nicaragua, where cattle grazing is very land intensive but profitable. Building roads to remote regions allows farmers to sell their cattle easily, with profits going to clearing more land to graze more cattle. New roads into the Amazon Basin and improved ports along the river will likewise spread soybean farming into areas that once were jungle, he predicts.

In place of the simple assumption that has guided many development projects in the past—that poverty is the cause of deforestation—Angelsen says that big plantation projects are more likely to contribute directly to deforestation than are small farmers. The challenges, he says, are to foresee how specific development strategies will impact a region's environment—displacing workers or making forest-clearing profitable, for example—and to identify projects that achieve both economic and ecological objectives.

Ultimately, says Kaimowitz, high-tech farming in the tropics should reduce the overall amount of land dedicated to agriculture, as it already has in the United States and Europe. “But that may or may not be relevant for saving the forest [today].”