# News this Week

Science  05 Sep 2003:
Vol. 301, Issue 5638, pp. 1300
1. THE COLUMBIA REPORT

# Vision, Resources in Short Supply for Damaged U.S. Space Program

1. Andrew Lawler

The debris from the space shuttle Columbia's catastrophic failure in February is finally hitting Washington, D.C. Last week's report (www.caib.us/news/report) on the tragedy calls for NASA to replace the aging shuttle fleet and takes the White House and Congress to task for not providing the vision and money for a robust human space exploration effort. Citing a “failure of national leadership,” the document puts pressure on the politicians to respond with clear goals and funding targets—an assignment that most would prefer to avoid.

The 13-member panel, formally the Columbia Accident Investigation Board, orchestrated a 7-month effort involving thousands of engineers and scientists, 30,000 pages of documents, and 10 public hearings. Led by retired Admiral Harold Gehman, the committee made dozens of sweeping recommendations designed to prevent another such disaster (see p. 1301). But members went far beyond a technical accident analysis, calling for a review of the entire U.S. human space program and laying out their own set of recommendations. “Look for a vigorous public policy debate about what we do now,” says Gehman. Adds Representative Dave Weldon (R-FL): “It's a discussion at least 20 years overdue.”

One important start, the report states, is to replace the remaining fleet of three orbiting shuttles, designed and built in the 1970s and 1980s. “This is likely to require a significant commitment of resources over the next several years,” according to the report. “The nation must not shy from making that commitment.” But the price would be huge, and paying it might require sacrificing other goals. NASA's science portfolio—roughly one-third of the agency's current $15 billion budget—could take a significant hit unless the agency gets a major infusion of new funding, say NASA officials and congressional staffers. NASA Administrator Sean O'Keefe hopes to focus attention on his plan for improvements to the shuttle, an alternative vehicle called the Orbital Space Plane, and billions of dollars in advanced launch, robotic, and human space-flight technologies. “This is a seminal moment in the agency's history,” he told reporters the day after the report was issued. NASA needs an extra$18 billion over the next 5 years to satisfy that vision, according to officials familiar with a preliminary agency plan developed this summer. The space plane alone would require more than \$12 billion of that additional funding.

But Science has learned that the White House rebuffed O'Keefe's initial plea last month for more money. Instead, senior White House officials plan to set up a working group to examine the cost of various options. The results would be laid out in the president's 2005 budget request to be released in February.

O'Keefe's prescription for human space flight is centered on the Orbital Space Plane, which would be designed to ferry astronauts to the space station using an existing expendable launch vehicle. But that approach has gotten mixed reviews in Congress: Some lawmakers prefer upgrading the current shuttle to building an expensive—and not necessarily safer—new system. NASA had hoped that the Department of Defense might provide financial support for a new vehicle, but talks broke down earlier this summer.

Looking beyond the lifetime of the shuttle and space station, O'Keefe touts a steppingstone approach beyond Earth orbit that would use humans only where robots aren't practical. The goal would be to extend scientific knowledge without aiming for specific destinations such as Mars. An outpost—either automated or with astronauts—between Earth and the moon, for example, might be used to assemble or inspect deep-space probes. For now, work would be confined to propulsion, robotics, and life-support research.

But such an approach also could be a hard sell in Congress. “Technology programs are not terribly efficient if you don't know what you want to do,” says one congressional staffer. “You need to tailor them for a mission.”

Any of these options will cost a lot of money, and the call for a big funding boost could not come at a worse time. The Gehman findings, released 26 August, appeared in major U.S. newspapers alongside a congressional report stating that the federal budget deficit is likely to hit a half-trillion dollars next year. And with a still-sluggish economy, a costly occupation in Iraq, and many other domestic priorities, NASA may find that a major new funding commitment is beyond its reach.

This week the House kicked off what will be a series of congressional hearings on the future of the shuttle, station, and overall NASA program. But lawmakers and their staff say the White House has to take the lead. “We're going to need clear direction from the president,” says Representative Sherwood Boehlert (R-NY), the House Science Committee chair. Weldon, a member of the House Appropriations Committee who represents the area around Florida's Kennedy Space Center, has proposed a 25% boost to NASA's budget over the next 3 years. But most other lawmakers supportive of the agency have refrained from calling for specific increases.

Reacting to the Gehman report, President George W. Bush said only that “our journey into space will go on.” He and his advisers have shown little interest in the civil space program, and the last White House attempt to press for an ambitious new mission—a 1989 call by his father for a mission to Mars—fell flat. NASA's O'Keefe himself recognizes that a repeat of President John F. Kennedy's 1961 moon-race challenge is not in the cards. “There is nothing comparable to what drove us as a nation with the threat of the prospect of thermonuclear war … in the early 1960s,” O'Keefe told reporters 27 August. He insists that science must be the driver for future missions, but his stance is none too popular among researchers long skeptical of the scientific benefits of sending humans into space.

Although leaders may not want to channel huge new sums to NASA, they can't stomach abandoning human space flight, either. Such a move would face strong opposition from aerospace companies, labor unions, and legislators representing districts in Florida, Texas, and California where NASA work is concentrated. It would also antagonize Russian, European, Japanese, and Canadian officials, whose countries have invested heavily in the space station.

“The path of least resistance is to make marginal changes to the shuttle, support the space station, and make incremental” investments in new technologies, says one congressional staffer. That outcome may be the best that this Congress and White House can do. But it would be a far cry from what the Gehman panel says is necessary to put the country's anemic space-flight effort on a healthy flight path.

2. THE COLUMBIA REPORT

# 'I Think I Added Something'

1. Charles Seife

From the start, Douglas Osheroff had some pretty big shoes to fill. “I was hyped as the Richard Feynman of this investigation,” he says of his role on the inquiry panel. “I am no Richard Feynman.” But like Feynman, Osheroff is a Nobel laureate and a physicist, and a little experiment—squirting liquids and gases under the rocket's insulating foam—injected a bit of drama into the accident probe.

In the 1986 Challenger investigation, Feynman's famous demonstration of an O-ring in ice water showed that the gaskets in the shuttle's solid rocket boosters couldn't handle low temperatures. Osheroff's efforts, which showed that evaporating liquids couldn't knock foam off the external fuel tank, exposed NASA's flawed theory that air getting underneath the foam liquefied and explosively evaporated, blowing the foam away.

That explanation didn't seem right to Osheroff, whose 1996 Nobel Prize honored his work with very low temperature liquid helium. Heat doesn't propagate through foam well enough to cause explosive evaporation a mere 81 seconds after launch, he knew. “So I asked myself, ‘Do I understand what's going to happen when pressure builds up?’” says Osheroff. “I realized it was rather complicated.”

It was a fairly simple setup: a foam block with a metal plate and a tube to inject liquids or gases. “We did the first experiment out on the loading dock [at Stanford],” Osheroff says. They moved outside, he says, because “we were afraid that [the food dye] would explode and shower dye everywhere.”

Every time Osheroff induced the foam to fracture, the break was perpendicular to the base of the foam. “[The dye] forces the foam sideways, not outwards,” he says. His conclusion: Something besides evaporating air—probably aerodynamic forces combined with structural defects in the foam—knocked off the foam.

Osheroff says he understands why the NASA engineers were misled into thinking that explosive evaporation was responsible. “Engineers have a different mindset than scientists,” says Osheroff. “They were building very complex models” and looking for the foam to fall off. In contrast, Osheroff tried to answer simple, basic questions about how the material would behave.

“I think I added something to the board,” says Osheroff. Nevertheless, he's disinclined to join another investigation board anytime soon: “It was an absolutely fascinating thing to do, but it took substantially more of my time than I expected.”

3. THE COLUMBIA REPORT

# Will a Safer Shuttle Still Support Science?

1. Charles Seife

The good news, says retired Admiral Harold Gehman, is that “the space shuttle is not inherently unsafe.” But the bad news, according to Gehman, the chair of the panel investigating the loss of the Columbia, is that “some things need to be done immediately” before NASA launches any of the three remaining shuttles.

When Columbia disintegrated over east Texas last February, it left NASA's human space-flight program hanging by a thread. Without a working shuttle, Russian rockets would have to ferry astronauts to work on the international space station (ISS). For space scientists, the consequences looked more serious: A planned mission to service the Hubble Space Telescope might be impossible.

The Gehman panel has recommended several steps that NASA needs to take to lower the odds of a future tragedy. The first addresses the flaw that caused the disaster: a piece of insulating foam that fell from a structure that connects the shuttle with its external fuel tank. The foam poked a hole in the shielding on the edge of the shuttle's left wing. That breach allowed superhot gas into the shuttle wing's aluminum skeleton during reentry, which within minutes caused the orbiter to break apart.

NASA has already addressed the proximate cause of the accident, replacing the foam with electric heaters. And NASA spokesperson Allard Beutel says the agency has also fixed another problem that the Columbia Accident Investigation Board identified, which involves a mechanism to prevent explosive bolt debris from slamming into the shuttle during booster separation.

To keep a closer eye on what happens during liftoff and flight, NASA will now routinely use “national assets” such as ground-based military telescopes and perhaps satellites to take pictures of the shuttle. Small modifications of existing cameras and procedures will provide better imagery, and orbiters headed to the ISS will pirouette so that astronauts on the station can take inspection pictures and send them to Earth for analysis.

The most difficult recommendation to implement, however, calls for a capability to repair the craft in space. Beutel says NASA plans to give astronauts “an applicator gun, like a caulking gun,” filled with a silicon-based material to fix cracked heat tiles. But damage to the leading-edge carbon composite structure, which is what destroyed Columbia, might not be easily repairable. “[Repairing carbon composite panels] is obviously more difficult,” says Beutel.

Inspections and repairs will be much harder on missions that don't go to the space station, such as one to repair the Hubble Space Telescope. A scientific panel assembled by NASA last month strongly urged at least one and possibly two servicing missions to keep Hubble operating (Science, 22 August, p. 1029). It's not clear how NASA will reconcile the conflicting goals of extending Hubble's life and keeping astronauts out of harm's way.

Nevertheless, the return-to-flight process is getting into high gear. In several weeks, a panel chaired by former astronauts Thomas Stafford and Richard Covey will begin to oversee NASA's attempts to get the remaining shuttles off the ground. A March date mentioned by NASA officials may be overly optimistic. But few doubt that the Florida skies will again be filled with the rumble of an orbiter launch.

4. INFECTIOUS DISEASES

# SARS Experts in China Urge Wider Animal Testing

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

TOKYO—The hunt for the animal reservoir harboring the virus that causes severe acute respiratory syndrome (SARS) edged forward on two fronts this week.

This week's online issue (www.sciencemag.org/cgi/content/abstract/1087139) contains findings from researchers who first implicated live wild animals in the transmission of the virus in a southern China market. At the same time, a joint team of experts representing the Chinese government, the World Health Organization (WHO), and the United Nations Food and Agriculture Organization (FAO) have agreed on recommendations for monitoring the live animal trade and searching for a SARS reservoir. Their advice— including a call for expanded animal testing and international cooperation—went to Chinese authorities on 5 September.

The study pointing to masked palm civets and other wild species as possible hosts of the SARS virus is the joint work of Yi Guan of the University of Hong Kong and his colleagues at UHK and the Center for Disease Control and Prevention in Shenzhen, Guangdong Province. The group announced its findings at a press conference last May before publication because of their implications for public health. Chinese authorities subsequently halted sales of 54 species of wild animals (Science, 30 May, p. 1351). Other researchers were unable to confirm those findings, however. Guan says an independent lab in the United States has confirmed his results.

In the meantime, Guan presented his results at a SARS conference in June in Kuala Lumpur. Albert Osterhaus, a virologist at Erasmus University Medical Center in Rotterdam, the Netherlands, says that the findings are now widely known and accepted, although researchers are eager to scrutinize the published details.

The Guan paper took a first step toward tracking down the animal reservoir, but much remains to be done, says Pierre Formenty, a WHO zoonotic disease specialist and co-leader of the joint team of experts submitting its report to Chinese officials: “Significant progress has been made, but there is a long list of next steps.” There is a pressing need to standardize the diagnosis of animal infections, he says. Many labs have used PCR and ELISA tests that are ambiguous because they give positive results for coronaviruses that may not be related to SARS. “We have to go for isolation of the virus as much as possible” to improve accuracy, Formenty says, and the results should be duplicated by a second lab.

Xu Jianguo, director of the National Institute of Communicable Disease at the Chinese Center for Disease Control and Prevention and a team co-leader, says other recommendations center on “strict and scientific ways of guaranteeing the safety of consumers” now that China has resumed trade in civets and other banned species. Only farm-raised animals can be sold, and the team is recommending that records be kept on each animal, tracking its life from farm to market. The report also calls for proper fencing to isolate farm animals from wild animals and new programs to screen animals for the virus.

Hume Field, a veterinary epidemiologist at the Queensland Department of Primary Industries in Moorooka, Australia, who represented FAO on the mission, admits that there isn't a practical animal test for the SARS virus as yet. He also notes that when such a test is ready, new studies will be needed to ensure statistical confidence.

Given such uncertainties, “I would have been more hesitant [than China was] to lift the ban,” says Osterhaus. He recognizes that the ban placed an economic burden on wildlife farmers. But the risks of reintroducing the SARS virus to humans are far more serious, he says.

The new recommendations call for more joint surveillance teams and greater cooperation both within China and internationally. Alan Schnur, WHO's team leader for communicable disease control in Beijing, says that there is already agreement on the need for further missions but that detailed plans are needed. He says, “We have got to be quick, because we want to get some of these answers before winter,” when many experts fear that the SARS virus could re-emerge.

5. PLANETARY SCIENCE

# Comet 'Factory' Found to Have Too Little Inventory

1. Govert Schilling*
1. Govert Schilling is an astronomy writer in Utrecht, the Netherlands.

On a typical beach, there are countless more grains of sand than boulders. Likewise, astronomers know that dwarf stars far outnumber giants and that there are more small meteorites than large ones.

But the icy outer reaches of our solar system appear to deviate from this rule of thumb. A meticulous search for small objects in this nether-space beyond Neptune known as the Kuiper belt has turned up fewer than 4% of the expected number. And that's a problem for astronomers, because the Kuiper belt is thought to be the source of the stream of comets that swing into the inner solar system. The result has left researchers wondering where the precursors of comets might be hiding. “This is very exciting work,” says small planetary body specialist Dan Durda of the Southwest Research Institute in Boulder, Colorado.

The Kuiper belt is made up of lumps of dirty ice—probably leftovers from the birth of the solar system—known as trans-Neptunian objects (TNOs). Most astronomers agree that Pluto and its moon, Charon, would be better classified as the largest TNOs. So far, more than 800 TNOs have been found, most of them more than 100 kilometers across.

Using the eagle-eyed Advanced Camera for Surveys on board the Hubble Space Telescope, a team of astronomers led by Gary M. Bernstein and David E. Trilling of the University of Pennsylvania in Philadelphia has carried out the first sensitive search for very faint (and hence relatively small) TNOs in a tiny patch of sky in the constellation Virgo. Based on the known numbers of large bodies, the scientists had expected the search to turn up some 85 TNOs down to 20 kilometers across. Instead, they found three.

In a paper submitted to the Astrophysical Journal, the researchers say that their results are “wildly inconsistent” with the observed number of short-period comets—comets with orbital periods of less than 200 years—that are believed to be small TNO escapees. As a result, they write, “models for the origin of [short-period comets] are missing some important process.”

The dearth of small bodies suggests that the Kuiper belt experienced an intense collision phase in which icy bodies smaller than about 100 kilometers in diameter were smashed to smithereens. “This new find is a valuable clue to the early collisional history of the outer solar system,” Durda says. He also points out that the new result may shed light on how easily TNOs are broken apart, which is a clue to their internal structure.

A similar deviation from the expected size distribution has been found in the more dense and rocky asteroid belt between the orbits of Mars and Jupiter, notes Durda. If the asteroid belt is any guide, the distribution of TNOs may be biased toward those with diameters of a few kilometers. Such small objects are harder to break apart by collisions.

If a future survey were to turn up a plethora of TNO pipsqueaks, these could be the wellspring of short-period comets.

6. INDIA

# Ayodhya Ruins Yield More Fuel for Ongoing Religious Fight

1. Pallava Bagla

NEW DELHI—Religious conflict runs deep in the Indian populace—and extends far underground. Last week, Indian archaeologists reported evidence of an ancient “massive structure” beneath one of the country's most sensitive religious sites. The results are expected to bolster claims by Hindus that a temple occupied the site long before a 16th century mosque and anger Muslims who see the results as another attack on their faith.

The Ayodhya site, excavated by the Archaeological Survey of India (ASI), is believed to be the birthplace of the immensely popular Hindu god Rama. In 1992 a mob tore down the Babri Masjid mosque, thought to be built in 1528 by the first Mughal king, Babur, and activists have demanded that a temple be erected in its place. In March the Uttar Pradesh state court ordered ASI to scientifically investigate the claim that a temple predated the mosque in hopes of resolving the land dispute (Science, 28 March, p. 1958).

Barely 2 weeks after completing an excavation of the 3900-square-meter site, ASI reported uncovering evidence of “50 pillar bases … indicative of remains which are distinctive features found associated with the temples of north India.” The 574-page report concludes that the pillar bases, with brickbat foundations below calcrete blocks topped by sandstone blocks, suggest a structure having a minimum dimension of 50 meters by 30 meters. The excavation also yielded a mutilated sculpture of a divine couple and carved architectural remains that include foliage patterns, an amalaka (a cogged piece of carved stone exclusively placed on the spires of north Indian temples), artifacts bearing a lotus motif, and a circular shrine having a pranjala, or water chute (another typically Hindu temple artifact).

R. C. Thakran, an archaeologist at the University of Delhi, says that the pillar bases highlighted in the ASI report appear to be “very fragile” and not sufficiently strong to hold up such a large structure. But Swarajya Prakash Gupta, chair of the Indian Archaeological Society and a veteran of previous excavations at Ayodhya, believes that “the report provides clinching evidence that a temple existed at the site.”

Although the report stops short of labeling the structure a temple, Hindu activists are already celebrating. Lal Krishna Advani, deputy prime minister of India and a strident Hindu leader, says the ASI report “gladdens crores [tens of millions] of devotees of Lord Rama.”

But Muslim organizations are prepared to challenge the findings. “There is not adequate proof in the report to establish the existence of a temple below the demolished structure,” says Qasim Rasool Ilyas, spokesperson for the All-India Muslim Personal Law Board. Dubbing the ASI report “perverse archaeology,” Irfan Habib, former chair of the Indian Council of Historical Research, believes that “the massive structure is a figment of the imagination.”

The court will hear from all sides before making a ruling, and nobody expects the scientific evidence to resolve the dispute. As the Indian Express warned in an editorial, “[further] discord, rather than resolution, appears imminent.”

7. MICROBIOLOGY

# Neither Cold Nor Snow Stops Tundra Fungi

1. Elizabeth Pennisi

A team of researchers has discovered a winter wonderland under the snow, populated by huge numbers and new kinds of microscopic fungi. These organisms are powerful, underappreciated drivers of tundra ecosystems, says Steven Schmidt, a microbiologist at the University of Colorado, Boulder. Their presence could force researchers looking at global climate change to revisit their models of where and how much carbon dioxide, nitrogen, and other substances are produced, he adds.

Until recently, researchers thought that cold temperatures suspended metabolism and growth of microorganisms in soil communities under the white blanket of snow. Schmidt, however, was puzzled to find that melting Colorado tundra snow released large amounts of organic nitrogen in the spring. Over the past 20 years, other biogeochemists had come across signs of life under the snow, such as unexpected quantities of methane and carbon dioxide. But only with the new study, on page 1359, is the extent of this hidden community revealed. Schmidt and his colleagues “demonstrate for the first time that undersnow soils are physiologically a very active environment,” says Ursula Peintner, a mycologist at the University of Innsbruck, Austria.

Schmidt's graduate student, Christopher Schadt, made visits to a snow-covered grass meadow in the Rocky Mountains for 3 years. He took soil samples during winter, the spring snowmelt, and the dry, sunny summer. With the help of microbial ecologist David Lipson, now at San Diego State University in California, Schadt found that the weight and volume of the fungi—their biomass—fluctuated seasonally, reaching the highest level during winter. “That this peak of biomass production is reached under the snow is an amazing result,” says Peintner.

Bacteria are the other abundant microbes in most soil communities. The proportion of fungi to bacteria varied seasonally, the samples revealed. In winter, fungal biomass was about 15 times that of bacteria, whereas in the summer the fungi were about six times more productive. The biomass of the fungi alone was about three times higher during the winter than the summer, and as the dominant organism, the fungi produced most of the carbon dioxide emanating from the snow-covered soil, Schmidt's team reports.

The seasonal changes make sense, says Cathy Cripps, a mycologist at Montana State University, Bozeman. During the winter, microbes must make do with cellulose-rich grass. Fungi are much more adept than bacteria at digesting cellulose, so they dominate the soil ecosystem. By summer, plant growth floods the soil with the starches and sugars that bacteria thrive on, and they catch up to fungi in abundance.

The researchers then determined what fungi they had gathered. “We expected these fungi would be the ones that people had studied before,” says Schmidt. But the DNA isolated from the soil samples told a different story. After matching 125 sequences against known fungal DNA, they discovered they had about 100 different kinds of fungi. These included specimens that represented three major new branches on the fungal tree, an amazing number that speaks to how much biologists have yet to learn about fungi, says Cripps: “These are really harsh environments, and yet there's still all this diversity.”

8. SCIENCE AND REGULATION

# A White House Mandate for More Peer Review

1. Jocelyn Kaiser

Is the government intent on improving its technical decisions or merely slowing down the regulatory process? That's a question critics raise about a new proposal from the Bush Administration to require agencies to peer review all scientific evidence that shapes a major regulatory decision. The guidelines, due out this week in the Federal Register, detail exhaustive procedures that agencies must follow, from tallying which documents will be reviewed to screening out anyone with a potential conflict of interest.

The new guidelines should raise the quality of federal rulemaking and lower the chances that the rules will be overturned in court, says John Graham, chief of the White House Office of Management and Budget's Office of Information and Regulatory Affairs. That's “good for consumers and businesses.” Some scientific experts take Graham at his word, noting that the proposal enshrines a basic scientific process. It's “an excellent idea,” says Harvey Fineberg, president of the Institute of Medicine. “Peer review is not going to eliminate controversy, but [it can] defuse one kind of criticism.”

But others worry that the changes will make it much harder for government agencies to issue new regulations. “Is it just another attempt to slow regulation?” wonders Ellen Paul of the nonprofit Ornithological Council. The notice discusses at length the potential corrupting influence of agency funding on academic scientists but is almost silent on industry-funded researchers, complains law professor Rena Steinzor of the University of Maryland School of Law in Baltimore: “This tilts the playing field.”

The draft guidelines supplement the Data Quality Act, a 2001 law championed by industry that sets out new standards for information released by government agencies. The rules apply to documents issued after 1 January 2004.

In suggesting that agencies do a better job of applying peer review, the draft bulletin proposes a sliding scale. For some documents, publication in a peer-reviewed journal might be sufficient. For “especially significant information,” however, an agency might need to assemble outside experts.

Agencies should also pay more attention to possible conflicts of interest. “Substantial funding” from an agency could disqualify a scientist, according to the guidelines, as well as publicly advocating a position on the matter at hand. A “biased” reviewer should be balanced by someone “with a contrary bias.”

The Environmental Protection Agency (EPA) is already following most of these steps, says science adviser Paul Gilman. “This is pretty standard stuff,” agrees Vanessa Vu, staff director for EPA's Science Advisory Board, which reviews the agency's major scientific documents. But Graham says the rules could require major changes at agencies such as the Department of Agriculture and the Army Corps of Engineers. The comment period ends 28 October.

9. CANCER RESEARCH

# Mutant Stem Cells May Seed Cancer

1. Jean Marx

Some cancers are sustained by a small minority of cells; their resemblance to normal stem cells might explain why many cancers are so hard to eradicate, and it has researchers rethinking cancer treatments

Stem cells have acquired a golden glow in the past few years as a possible tool for reversing the damage diseases wreak on organs. Many researchers predict that stem cell transplants—whether derived from embryonic tissue or from adult cells that retain the flexibility to develop into various tissues—will someday repair hearts crippled by heart attacks or brains under attack by Alzheimer's or Parkinson's disease. But the very qualities that make these cells so attractive for medicine—especially their capacity to replicate ad infinitum—also hint at a dark side. Recent evidence suggests that they may be the source of the mutant cells that give rise to cancerous tumors and maintain their growth.

Researchers have identified what they call “cancer stem cells” in blood cancers, such as leukemias, and in breast and brain cancers. The finding raises the possibility that the mutations that drive cancer development may have originated in the body's small supply of naturally occurring stem cells. Cancer stem cells resemble those normal cells in several ways. In particular, both types are self-renewing. This means that when they divide, one of the daughter cells differentiates into a particular cell type that eventually stops dividing, but the other retains its stem cell properties, including the ability to divide in the same way again.

The new work shows that cancer stem cells, which form only a small proportion of the total tumor cell population, are the only tumor cells with the capacity to keep tumors growing. “Most people think that cancer is cells that grow too much, but only one in a million [leukemia cells] has the ability to sustain the disease,” says stem cell biologist John Dick of the University of Toronto.

Irving Weissman, a stem cell expert at Stanford University School of Medicine in California, describes the therapeutic implications of the work as “absolutely huge … it has the chance of leading to new ways of thinking about cancer and new kinds of therapies.” To cure cancer completely, Weissman and others say, it may be necessary to design therapies that target cancer stem cells, assuming that can be done without also wiping out the stem cells needed to maintain tissues such as the bone marrow and intestinal lining. In addition, the growing suspicion that stem cells may be the source of some cancers sounds a note of caution for efforts to use stem cells for organ repair.

The idea of cancer stem cells has been kicking around for 40 years. An early indication that such cells might exist came from the finding that just 1% or less of leukemia cells grow and form colonies in lab dishes. This implied that only those few cells could drive tumor growth in patients, but the work more or less petered out in the mid-1970s because researchers weren't able to assess the carcinogenic potential of the cells in living animals. Only in the early 1990s did that begin to change, aided by a mouse model Dick and his colleagues were using to study the development of human hematopoietic stem cells, which give rise to the various types of blood cells.

The model starts with an extremely immunodeficient mouse strain called the NOD/SCID mouse. The researchers irradiate the animals to destroy their bone marrow and then introduce human stem cells to see if they will produce a new complement of blood cells. After showing that normal human hematopoietic stem cells can do this, Dick and his team used the approach to study the cancer-causing power of acute myeloid leukemia (AML) cells freshly harvested from human patients. By progressively diluting a known number of leukemia cells, they established that only the very rare AML cell—about one in a million—has the ability to reproduce the disease in the animals.

Because this was a much smaller fraction of cells than could form colonies in culture, the result indicated that the simple ability to grow didn't equate with the ability to develop into leukemias in living animals. Dick speculated that the leukemia-initiating cells had a greater developmental potential than the vast majority of clone-forming cells and might even be stem cell-like.

The Toronto team provided direct evidence for that supposition. They characterized the leukemia-initiating cells according to surface proteins called markers that distinguish the various cell types of the hematopoietic system. The leukemia-initiating cells turned out to belong to an exclusive group. They were positive for the CD34 marker and negative for CD38—the same as human hematopoietic stem cells—and did not carry markers of more mature cells. “They're very similar to normal stem cells,” Dick says.

The cancer cells' resemblance to normal stem cells held up even though AML is a heterogeneous disease, with several different subtypes depending on which genetic abnormalities the patients' cells carry. Dick and his colleagues characterized the leukemia-initiating cells from the various AML subtypes and found that all belonged to that same CD34+/CD38 class. When put into NOD/SCID mice, however, each cell type produced a leukemia identical to that in the patient from which it had originally been isolated. All in all, Dick concludes, it's likely that the initial mutations that gave rise to the leukemias arose in normal stem cells, causing them to take the wrong developmental pathway.

Stanford's Weissman has come to a similar conclusion by tracing a common genetic abnormality leading to AML. This is the so-called 8;21 chromosomal translocation, in which the AML gene on chromosome 21 is fused to the ETO gene on chromosome 8, thus leading to production of an abnormal hybrid protein that alters gene expression. Weissman found the translocation both in stem cells and in more mature blood cells of several different types in AML patients. That suggests that the translocation originated in a stem cell that then gave rise to the different mature cells as well as replicas of itself.

But even though the translocation is necessary for this type of AML to develop, Weissman says it is not sufficient. Stem cells that were isolated from patients in remission and carried the abnormality, he and his colleagues found, differentiated normally in culture. This indicates that additional mutations, possibly occurring at a later developmental stage, are necessary to produce leukemia. Unlike Dick, who sees the original hematopoietic stem cell as potentially leukemic, Weissman thinks that the leukemia stem cell may be one or more steps down the differentiation pathway.

The cells of solid tumors are harder to isolate and study than those of the hematopoietic system, but recent evidence suggests that solid tumors also contain stem-like cells. Some of it comes from research on breast cancer by Michael Clarke and his colleagues at the University of Michigan Medical School in Ann Arbor. They, too, used the NOD/SCID mouse to assay for cells able to initiate cancer, in this case injecting human breast cancer cells into mouse mammary glands.

The Michigan team found that, as with AML, only a small fraction of breast cancer cells form tumors in the NOD/SCID mouse, as reported in the 1 April issue of the Proceedings of the National Academy of Sciences. These cells could be distinguished from non-tumor-initiating cells based on their surface markers. (They were CD44 positive, CD24 negative or low.) “We can prospectively identify cells that are capable of driving tumor growth and metastasis,” Clarke says.

At present, Clarke and his colleagues can't be positive that the cell population they identified is derived from normal stem cells. But the cancer-initiating cells possess the key stem cell characteristic of self-renewal. The tumors growing in the mouse mammary pads contained their own small populations of CD44+/CD24−/low cells, which could be isolated and used to initiate tumor growth in other mice. It's still possible, however, that more mature cells regained the ability to self-renew, Clarke says.

Mutant stem cells may seed brain tumors as well. In work due to appear in the 15 September issue of Cancer Research, a team led by Peter Dirks at the Hospital for Sick Children in Toronto isolated an apparent stem cell for brain cancer. The researchers found that a variety of brain cancers, from relatively slow-growing astrocytomas to highly aggressive medulloblastomas and glioblastomas, contain small populations of cells with very similar, stem cell-like properties. They carry markers previously associated with normal neural stem cells and do not have markers characteristic of more differentiated cells. The cells also had the ability to self-renew and to differentiate, at least in lab cultures. Together, these qualities suggest that the different types of tumors derive from a common stem cell population, Dirks says.

Further support for the idea that brain tumors originate in stem cells comes from Luis Parada of the University of Texas Southwestern Medical Center in Dallas and his colleagues. They created a mouse model of brain cancer by mutating an oncogene called neurofibromatosis 1 along with the p53 tumor-suppressor gene in an early precursor of brain neurons and other cells. The mice develop numerous brain tumors, Parada reported in February at a meeting of the American Association for Cancer Research. Imaging studies showed that although the tumors can end up anywhere in the brain, they all originate in two areas, the lateral ventricles and hippocampus—both places where brain stem cells are located.

Preliminary evidence suggests that the proportion of stem cells in a tumor may determine how deadly it is—a finding that could have prognostic implications. Dirks found that fast-growing medulloblastomas and glioblastomas had many more putative tumor stem cells than astrocytomas had. And Clarke notes that an extremely aggressive breast cancer that he studied contained about 25% stem cells. He cautions, however, that so far researchers have studied tumors from only a small number of patients, and more work will be needed to confirm these findings.

## A common path

Another line of evidence suggesting that cancers originate from stem cells comes from studies of the biological machinery underlying self-renewal. Normal and cancer stem cells show some striking similarities. Recently, for example, researchers have shown that the genes Bmi-1 and Wnt, both of which can cause cancer when mutated, are needed for self-renewal in normal and cancer stem cells.

The Bmi-1 gene participates in normal hematopoietic development, and its malfunction has been linked to AML. In work reported in the 15 May issue of Nature, two teams, one led by Clarke and Weissman and the other including Guy Sauvageau of the University of Montreal and Julie Lessard of the Clinical Research Institute of Montreal, link the gene to self-renewal.

To test whether cells missing Bmi-1 can self-renew, the researchers transplanted stem cells from Bmi-1 knockout mice into normal mice that had been irradiated to destroy their bone marrow. The stem cells produced a normal complement of blood cells—but only briefly. By 8 weeks, blood cells derived from the transplanted cells had almost disappeared, and when bone marrow taken from the animals was put into a second series of mice, no Bmi-1-deficient blood cells could be detected.

Bmi-1 is also needed for the self-renewal of leukemia cells, Sauvageau and Lessard showed. About 5 years ago, Sauvageau and his colleagues discovered that they could cause an AML-like disease in mice by introducing two oncogenes, Meis1a and Hoxa9, into the bone marrow cells of the animals. In the current work, Sauvageau and Lessard introduced these genes into fetal liver cells, which contain hematopoietic stem cells, from normal mice and animals in which Bmi-1 had been inactivated.

Altered cells from both types of mice transiently produced leukemias when transplanted into irradiated mice, but the cells lacking Bmi-1 could not be transmitted to a second set of recipients. This result shows that without Bmi-1, leukemia stem cells die out, just as normal stem cells do.

The Wnt gene is likewise the focus of a great deal of research by both cancer researchers and developmental biologists. The protein encoded by the gene normally controls cell fate decisions during the development of many of the body's tissues. It exerts its effects by binding to, and thus activating, a receptor on the cell surface membrane. This in turn sets off a series of changes inside the cell, culminating in the activation of genes governing cell division and differentiation.

Evidence suggests that operation of this pathway, sometimes called the “Wnt cascade,” is needed for stem cell maintenance. For example, about 5 years ago, Hans Clevers of the University of Utrecht in the Netherlands and his colleagues created a strain of mice in which the gene encoding a protein called Tcf-4 had been knocked out. Tcf-4 operates at the end of the Wnt cascade, working with certain other proteins to activate gene expression in response to Wnt signals. Animals lacking the gene died shortly after birth and displayed a single defect: The stem cells that produce the lining of the intestines appeared to be missing. The Wnt cascade is also needed for self-renewal of hematopoietic stem cells, Weissman's team in collaboration with Roel Nusse, also at Stanford, and his colleagues reported a few months ago.

Abnormal activation of the Wnt pathway, and presumably of self-renewal, can lead to cancer. For example, the APC gene, which is mutated early in the development of 90% of colon cancers, is part of the Wnt cascade. As a result of this mutation, Clevers says, “you have an active Wnt cascade without [an incoming] Wnt signal.”

Consistent with that, Clevers and his colleagues have found that gene expression patterns in colon cancer cells look a lot like those in colon stem cells. Using DNA microarrays, the researchers analyzed the changes produced by Wnt signaling in colorectal cells. Wnt up-regulates 120 genes and down-regulates 115, they reported in the 18 October 2002 issue of Cell.

When the researchers then looked at normal cells of the gut, they found a similar gene expression pattern in the areas where colon stem cells are located. In contrast, in the areas where differentiated cells are located and Wnt signals are presumably not present, the pattern was just the opposite: The 120 genes up-regulated in the cancer cells were turned down, and those that were down-regulated were turned up. Mutations in the pathway “activate a situation where cells can't shut off the stem cell program,” Clevers concludes. That locks cells with the mutations into a proliferative state during which they can accumulate additional mutations that ultimately produce full-fledged cancers.

Other researchers, including Elaine Fuchs of Rockefeller University in New York City and Fiona Watt of Cancer Research UK's London Research Institute, have shown that the Wnt pathway controls cell fate decisions in the epidermis of the skin. Here, too, malfunctions in the pathway can lead to tumor development. The Fuchs team found evidence that mutations that abnormally activate β-catenin, a key component of the Wnt pathway, cause pilomatricomas, a benign tumor of the hair shaft in humans.

## Forewarned

Despite the growing evidence that some cancers arise in stem cells, the case isn't airtight. But those favoring the idea offer two additional arguments. First, stem cells already have the ability to self-renew, whereas more mature cells would somehow have to regain it if they were to turn cancerous.

Second, especially in organs such as the skin and colon lining, where older cells are constantly dying and sloughing off, stem cells may be the only cells that hang around long enough to accumulate the several mutations needed to produce full-fledged cancers. “Cancer [development] is long-term,” Sauvageau says. “You can't have a cancer develop in a [cell] that is short-lived.”

But even if cancer doesn't originate in normal stem cells, tumor growth apparently depends on a small population of stemlike cells that may differ from the bulk of the tumor population in ways that make them resistant to therapy. Current cancer treatments “may not be hitting the cells that can make the tumor come back,” Dick says.

In particular, many cancer therapies are designed to kill dividing cells. Somewhat surprisingly, stem cells are mostly quiescent. They apparently wake up to divide only occasionally—a lifestyle that means they will likely escape the cell-killing effects of standard therapies. Researchers may therefore need to find ways to wipe out cancer stem cells.

And beyond implications for cancer therapy, the findings raise concerns about efforts to use stem cells to treat other diseases. Dick and others working on cancer stem cells note that many potential applications require that stem cells be forced to divide to produce enough cells to replace damaged tissue, and that might facilitate the accumulation of potentially cancer-causing mutations. “We need to think carefully about that,” Dick says.

Weissman points out, however, that even if a stem cell had an initiating mutation, such as the 8;21 translocation of AML, accumulation of the additional mutations needed to produce a cancer would still be relatively unlikely. He cites his team's finding that stem cells bearing the translocation obtained from patients in remission differentiated normally in culture. Many of those patients had been in remission for 15 years or longer, and during that time their stem cells hadn't acquired the additional mutations that would have rekindled leukemia.

Defensive measures may also be possible based on the growing understanding of how stem cells can turn bad. Modern methods of marker analysis and cell-sorting may make it possible to identify and then eliminate cells bearing dangerous mutations. As Cervantes put it: “Forewarned, forearmed; to be prepared is half the victory.”

10. RONALD PLASTERK PROFILE

# TV Fame and RNA Glory

1. Gretchen Vogel

A Dutch molecular geneticist proves as deft at dissecting the political scene as he is at analyzing transposons and RNA

UTRECHT, THE NETHERLANDS—Ronald Plasterk says he didn't intend to bring down the government when he predicted on national television on 14 April 2002 that Prime Minister Wim Kok would step down. Although Kok was embroiled in a scandal over allegations that Dutch troops could have done more to prevent the massacre of Bosnian Muslims in Srebrenica in 1995, most observers expected him to stay in office until after elections set for 15 May. But 2 days after Plasterk's commentary, Kok led a resignation en masse of the entire Cabinet. An aide told reporters that Plasterk's remarks had helped seal Kok's decision.

A member of Kok's center-left Labor Party, Plasterk also happens to be a molecular geneticist and co-director of the Hubrecht Laboratory here in this university town an hour south of Amsterdam. He has won acclaim for his lab's work on self-replicating stretches of DNA called transposons and more recently in the hot field of interference RNA (RNAi), small RNA molecules now known to play important roles in gene regulation and other processes (Science, 20 December 2002, p. 2296).

But it's his media moonlighting that has made Plasterk a household name in this country of 16 million people. He writes a weekly column for the Volkskrant, one of the Netherlands' leading daily newspapers, and every other week he presents a two-and-a-half-minute commentary on the Sunday talk show Buitenhof, the Dutch equivalent of Meet the Press. Although he is introduced as a scientist, his commentaries stray far from the lab, covering topics from the war in Iraq to the role of religion in society. “His combination of talents is unique. Not rare, unique,” says molecular biologist Piet Borst, former director of the Netherlands Cancer Institute. “Not only is he an outstanding scientist and outstanding communicator of science, but he is also a shrewd and knowledgeable political commentator.”

Plasterk knows it, too. “You would have to call him a bit ijdel, which translates as ‘vain,’ but that's not quite right. People tend to hate people who are vain, but Ronald is very much appreciated,” says developmental biologist Hans Clevers, co-director of the Hubrecht Laboratory. “His talents stand up to everything he says.”

Plasterk's media star began rising in 1993, when the editor of a magazine at the Free University in Amsterdam invited him to pen an occasional column. After a 4-year stint writing for the weekly Intermediair magazine in Amsterdam, Plasterk signed on as a Volkskrant columnist. Broadcasting fame beckoned in 1999, when Buitenhof producers asked Plasterk if he'd give television a try. “Presenting a column [on Buitenhof] makes you by far the most influential scientist in the Netherlands,” says Borst. “The top politicians are on the show, and so he meets and interacts with all of them.”

When the occasion arises, Plasterk does not hesitate to wield his scientific authority. Last January, when members of the Raelian sect claimed to have produced their second cloned baby in the Netherlands, Plasterk used his TV appearance to call their bluff. He volunteered to visit the supposed mother and baby “with a notary and two cotton swabs” for genetic testing. Within 24 hours, he promised, Hubrecht's sequencing machines could yield a definitive answer. The Raelians declined his offer.

His scorn can be a powerful weapon, says Borst, for example when in a 2001 program Plasterk pilloried homeopathic remedies as “garbage.” A regulation had just taken effect in which pharmaceutical firms had to demonstrate that products are manufactured according to reproducible techniques. Homeopathic remedies do not meet that standard, Plasterk argued, and as he spoke, he disdainfully poured various colorful homeopathic tinctures and pills into a beaker on his podium. The dismissive commentary provoked a spate of angry letters. “It's amazing how seriously homeopathy is taken by intellectuals,” Plasterk says.

“I wish there were someone like him in the United States,” says Dutch expatriate Roel Nusse, a developmental geneticist at Stanford University in California. “He is remarkably effective in explaining in simple terms what is important in science.”

That talent has also served him well in the scientific arena. With Christiane Nüsslein-Volhard of the Max Planck Institute for Developmental Biology in Tübingen, Germany, he helped persuade leaders at the Sanger Institute in Hinxton, U.K., to make sequencing the zebrafish genome a top priority as the Human Genome Project was winding down a few years ago. (Developmental biologists prize the fish for its see-through embryos that allow easy observation of organ development.)

Plasterk had worked for several months in 1985 as a visiting scientist in former Sanger director John Sulston's lab. “I knew the right buttons to push,” says Plasterk, who pleaded on behalf of the scores of postdocs struggling to track down the genes responsible for intriguing mutations produced in large-scale screens. “It was really he and Janni [Nüsslein-Volhard] who swung it,” says Sulston. “They provided a very good basis to go forward.” Plasterk's lab is now taking advantage of the nearly completed sequence by pioneering the use of fast sequencing to hunt for mutations in target genes.

What most excites Plasterk at the moment is his work on RNAi. He has promoted the concept that the RNAi machinery serves as a sort of immune system for the genome, protecting it against the runaway duplication of transposons (Science, 17 May 2002, p. 1263). Such a system is present in plants and nematodes, says Plasterk, but its role in vertebrates, including humans, is murky. “I like the romantic phase” of a research program, he says, “where you're trying to find out what the hell is going on.”

“The stuff he's doing now is gorgeous,” beams Plasterk's former postdoctoral supervisor, molecular biologist Melvin Simon of the California Institute of Technology in Pasadena. “I got so turned on that we shifted a whole section of our lab to RNAi. … He's one of these people who keep looking for the edge of a field, and when they find it they seem to know what to do.”

Plasterk's colleagues fret that his star power may whisk him out of research altogether. “Our great worry is that he will be arm-twisted into becoming minister for science and education,” Borst says, if Labor were to join a ruling coalition after elections due in 2006. “It would be a pity for science if he left. On the other hand, he could do a lot of good as a capable and sound minister. … He really is a man for big jobs.” When asked about his political ambitions, Plasterk is demure: “I want to stay in science. Having said that, one never knows how life will go.” One of his favorite quotes, he says, is by the chess master Jose Raul Capablanca, who when asked how many moves he thought ahead replied, “One, but it's always the right one.” Plasterk, it appears, has made all the right moves so far.

11. FATHERS AND CHILDREN PROFILE

# Inheriting the Family Science

1. Richard A. Kerr

Children who enter the same earth science niche as their fathers did start early with a general interest in the natural world but eventually absorb paternal predilections

There's no doubt that Timothy Eglinton has entered the family business. He labors in surroundings familiar from childhood trips to his father's workplace and turns out products very much like those his father, Geoffrey Eglinton, made for more than 40 years before retiring. And the son enjoys the instant name recognition among colleagues that his father so assiduously developed. But Eglinton fils hasn't inherited the family bagel business or assumed his father's position as CEO of an automotive giant. Rather, he has followed his father into science. And not just earth science, or oceanography, but marine organic geochemistry. He is analyzing life's rotten remains just as his father did before him.

Unlike in private business, where the next of kin inherit by default, there are no traditions ensuring such faithful scientific succession. Quite the contrary; pretenders to a seat in science must prove themselves doubly worthy if they carry the name of a leading figure in the very field they aspire to. Why then would a son or daughter ever try to emulate so closely a scientist parent? In science, observes the elder Eglinton, “there's very strong pressure for the child not to follow the parent. It still puzzles me how it all happened” in his family.

Earth scientists are not the only ones who take up the family vocation, of course, but it seems to be a surprisingly common occurrence in the discipline. Science has identified at least a dozen prominent earth scientists whose children have entered the same subfield in which they specialized. The routes to scientific familial succession vary, but there seem to be some common patterns. It generally happens without the father or child quite intending it. (Fathers overwhelmingly predominate among earth scientists old enough to have earth-scientist offspring.) Typically, the child displays an early interest in science, especially in the world around him or her. The father's own interests and vocation inevitably nurture any penchant for the things of Earth and sky, but not necessarily in an “I want to grow up to be just like Daddy” way. Often the child takes only a general interest in the field until the father arranges a firsthand experience in earth science research, sometime between high school and graduate school. But even then, concern about being overshadowed can be a strong disincentive. “I continue to have reservations,” says Timothy Eglinton. Eglinton père “is such a tremendous figure in our discipline. He was defining the discipline; I'm working in it.”

## An early start

Putting a finger on the ultimate origins of earth scientists may be impossible, but they are generally rooted early in life. “I was always interested in natural history,” says Timothy Eglinton. “I had a lot of weird pets,” in the line of snakes, lizards, and turtles, as well as the mouse colony needed to feed the snakes.

Atmospheric geochemist Ralph Keeling tells a similar story. He works not only in the same field but the same institution as his father, the Scripps Institution of Oceanography in La Jolla, California. Ralph Keeling makes precise measurements—precise to six significant figures—of the oxygen in the atmosphere. That allows him to track the comings and goings of carbon passing through atmosphere, oceans, and plants, a prime concern of greenhouse warming researchers. His father, Charles “Dave” Keeling, has been at Scripps 47 years and also tracks carbon in the atmosphere, ever since he started his pioneering measurements of atmospheric carbon dioxide atop Mauna Loa in Hawaii in the mid-1950s. Every plot of inexorably rising carbon dioxide concentrations in the atmosphere over the past half-century depends on his data.

For Ralph Keeling, early signs of scientific interest came at age 2, when he was just learning to talk. On a summertime trip to the Cascade Mountains, Charles Keeling recalls, the family was admiring Nisqually Glacier when Ralph piped up, “How do you make glaciers?”

Climatologist David Changnon of Northern Illinois University in DeKalb “always had an interest in severe, unusual weather,” he says. He now investigates how climate data can be put to work for electric utilities, airlines, and insurance companies. His father, Stanley Changnon, a climatologist retired from the University of Illinois, Urbana-Champaign, and the Illinois State Water Survey, probably inspired his specific interest in weather. But his natural history interests went deeper than that, says Stanley. David “was obviously curious about the physical world and had a keen interest in his surroundings. We'd be on a trip, and he'd ask, ‘What's that?’ ‘That's a recessional moraine’ “—a mound of debris dumped by a retreating glacier—his father would answer.

Of course, not every parent would be able to answer a question like that with such scientific specificity. These fathers were in a position to feed their children's budding interest with information and accustom them to scientific habits of thought. A good example is a conversation Jason Phipps Morgan recalls having with his father. The younger Morgan is a tectonophysicist at the GEOMAR Research Center for Marine Geosciences in Kiel, Germany, where he considers how the inner workings of plate tectonics such as midocean ridges operate; his father, W. Jason Morgan of Princeton University, was a pioneer in the plate tectonics revolution of the 1960s, proposing great plumes of rising hot rock to explain Hawaii, Iceland, and other volcanic hot spots.

At age 7 or 8, young Jason was unaware of his father's stature in the earth sciences. But stuck at home one day with the mumps and bored, the boy picked up a Bible for the first time and started wondering about how the Red Sea could part. “I brought it up with Dad,” he recalls. Another father might have talked about faith and miracles, but the older Morgan turned the discussion to science. “I learned that people did worry about whether walls of water could be stable,” the son says.

In the Melbourne family, “there was an undertone of rationalism, an analytical approach to the world,” says seismologist Timothy Melbourne of Central Washington University in Ellensburg. He studies earthquakes of all sorts, especially “silent” quakes, using the distance-measuring technique called the Global Positioning System (GPS). His father, William Melbourne, is retired from the Jet Propulsion Laboratory in Pasadena, California, where he helped develop GPS for use in geophysics. “Everybody who studies earthquakes with this technology knows my dad,” says Timothy.

“‘Use your brain and figure it out’ was the attitude in our family,” Timothy recalls. One vivid memory involves blue street reflectors. Most reflectors marking lanes in his neighborhood were red or orange, but once in a while he'd see a blue one. “What's the deal?” he asked his father. “Figure it out for yourself,” his father replied. Timothy eventually deduced that the blue ones marked the roadside location of sometimes-obscured fire hydrants, but he never did get any help from his father.

“That's why my sister and I went into science,” he says. (Ruthann Melbourne has a Ph.D. in mathematics and now works on Wall Street.) “My dad was never an overbearing ‘science’ expert,” Timothy adds. “He never said ‘You have to be a physicist.’” The nonverbal message did come across, however, that “going to law school or med school was just not something we would do.”

## Field trips, colleagues, and siblings

Field trips and the influence of the father's colleagues often helped cement this early interest in the natural world. David Changnon remembers his father taking him at age 7 to see the damage from a major tornado outbreak and at about age 10 to see the field instrumentation recording the effects of urban development on weather. G. Randy Keller is a geophysicist at the University of Texas, El Paso, who probes the continents tens of kilometers down using artificial seismic waves. His son William, in his first job out of the California Institute of Technology, is working on better ways to image oil and gas deposits using wavelet analysis of artificial seismic waves. Both he and his sister, now a CPA, “got several trips around the world” to Europe, Africa, and Australia, says their father, as Randy collected seismic data on the continents. There the children met scientists involved in the same field experiments. “A couple of these people are like uncles to the kids,” Randy says.

More often than not, however, siblings do not share the future earth scientist's penchant for the natural world. And scientifically minded siblings tend to choose a different field, as Ruthann Melbourne did. Michèle Morgan, Jason's sister, says, “I was always more interested in biology and life. I preferred trees over volcanoes. I took physics, but I always struggled; my brother got all the physics genes.” She is now a biological anthropologist at Harvard University's Peabody Museum.

## Commitment, sooner or later

By the time the future earth scientists reached college, they were sold on a career in science—not the science their fathers were doing, but engineering, perhaps, or theoretical physics or hydrogeology. Yet, in each case, a life-changing experience intervened. Sometimes it was an earth science course they took just for the fun of it, but most typically it was a work experience arranged by the father.

For climatologist David Changnon, that career-altering experience came exceptionally early. “From the time he was very, very small, David had a desire to be with me,” says Stanley Changnon. “In late junior high or early high school, we were having a run of bad winters, and I was doing a series of research reports on the storms in Illinois. ‘Would you like to help?’ I asked. He said, ‘Oh yeah, sure.’ I got him into plotting dates and isolines on maps.” Says David: “I really got turned on by those awful winters.” Writing them up was not just fun, he says—it also netted him his first publications, years before finishing a general engineering degree and entering graduate school in atmospheric science.

Jason Phipps Morgan's first exposure to research came later, but it altered his plans more immediately. “When I went off to college, the one thing I knew was that I wasn't going to do what my father did. But freshman year, my father got me a summer job as a programmer. It was pure nepotism.” The job was in geophysics at the University of Hawaii, where his father was temporarily working. Jason's project involved the ocean crust's magnetic striping, a key to the plate tectonics revolution, so he read some of the related literature. “I learned I liked these [geophysics] papers,” he says. “I really liked the unsolved nature of earth science.” By sophomore year he was taking earth science courses on his way to a Ph.D. in geophysics.

In college, Ralph Keeling had been considering theoretical physics, not his father's work with analytical instruments. But after one semester of graduate school at Harvard, he joined his parents in Switzerland, where his father was on sabbatical. With his father's encouragement, he joined a project of the late Hans Oeschger developing a breakthrough technique for extracting gases trapped in glacial ice over the millennia. “That galvanized my interest in being an instrumentalist,” says Ralph. He went on to develop a novel interferometric technique for measuring atmospheric oxygen so precisely that its combination with carbon could be followed.

Wendy Mao's epiphany came later still. Her father, Ho-kwang “Dave” Mao of the Carnegie Institution of Washington's Geophysical Laboratory, is a leading researcher in high-pressure mineralogy. He squeezes and heats bits of deep-Earth materials to see how they behave. But Wendy “had managed to be completely ignorant of earth science,” she says. “He never really mentioned it much.”

Wendy Mao went into materials science as a graduate student at the Massachusetts Institute of Technology. Burned out after a couple of years, she returned home, where “Dad said, ‘Why not come to the Geophysical Lab and maybe you'll be interested in something there.’” After some father-daughter discussion, she worked on how water ice under pressure can incorporate hydrogen molecules—which is relevant to the formation of small icy moons. Six months of work netted her a first-author credit on a report in Science last fall (27 September 2002, p. 2247). Now she's in graduate school at the University of Chicago working on the behavior of iron under the conditions in Earth's core.

## Close colleagues

When you start work in your father's subdiscipline, the obvious next step is the ultimate familial collaboration: co-authorship. It can be a rewarding experience—and sometimes a bit of a strain.

The Changnons and the Maos got an early start. The Morgans waited 8 years after Jason Phipps Morgan finished grad school but are now working on their sixth joint paper. “I got my father back into some midocean ridge questions,” says the younger Morgan. “We spent a whole Thanksgiving talking about midocean ridges, until my mother told us to shut up. He has a really good nose for what might work or not work. Bouncing things off him, you get a lot more return than with most people.”

Jason Morgan's father sees their collaboration as a two-way street. “Jason has a lot of techniques I don't have,” he says. “He would see a way to solve a problem that to me would have been very difficult.” Such complementarity seems to be common among parent-child pairs. “I don't have the writing skills that my dad has,” say David Changnon. “I'll send papers down to him for editing.” When Geoffrey Eglinton came across a “weird … crazy” paper on hydrocarbons found in Yugoslavia, his son had just the right lab techniques to sort out the weirdness. “That was quite pleasing,” says Geoffrey.

Familial collaboration can have benefits beyond publication. “It's been a pleasure to share life with a parent who shares an interest in science,” says Jason Phipps Morgan. Wendy Mao says, “Now I can talk to my dad about his science. Our relationship has developed a lot the last couple of years. I've gotten to know him a lot better.” The parents appreciate the closeness as well. His son “is a wonderful outlet” for anything climatological, says Stanley Changnon. “It's a blessing in my life.”

Such collegial closeness can have its rough spots, however. “It can be hard to engage at a deep scientific level someone you've squabbled with as a child,” notes Ralph Keeling. “I get along great with my father, but our conversations aren't always smooth.” Who's in charge of an exchange of scientific views isn't always clear, he says. Parents face adjustments too. During the preparation of a recent joint paper with his son, Geoffrey Eglinton “was careful not to be too much of a nuisance,” he says. He had expected things to get done on his schedule, as they had when his son was young. In fact, he says, things got done when Timothy found time to do them.

The biggest concern in the parent-child scientist relationship is the looming stature of the parent. The problem is only compounded for earth scientists. The parents began their careers in the 1950s and '60s, when they had a chance to found and expand whole new fields in the suddenly rejuvenated earth sciences. There are different paths to avoiding being outshone by a father. “My dad has cast a pretty big shadow in the [climatology] community,” says David Changnon. “I still worry about that to a degree. How do I become different?” He's advised many students at Northern Illinois, whereas his father never taught. He has focused on how decisionmakers can make better use of climatological data. And he has no ambitions of being the broad generalist that his workaholic father has been.

Ralph Keeling intended to set himself apart from the start. “I wanted to earn what came with the name,” he says. “The project I took on [in graduate school] was fairly risky. I set the bar pretty high because when in your father's field, you want independent name recognition.” In the end, of course, there can be no complete independence when family ties are so strong. And no one seems to wish it.

12. HONG KONG

# Science University Fears Merger Could Weaken Research Program

1. Dennis Normile

Can a young and successful science university find happiness with an older, larger institution? Hong Kong waits for the answer

TOKYO—By all accounts, the Hong Kong University of Science and Technology (HKUST) is a 12-year-old experiment that is working well. But perhaps not for much longer. The government is currently examining the possibility of merging HKUST with the older, larger, and comprehensive Chinese University of Hong Kong (CU).

Overwhelmingly, HKUST's world-class faculty see the proposal as a threat to the very qualities that have allowed the school to excel: a tightly focused research agenda and the training of a small but selective student body. But government officials, who are confronting a financial crisis in this former British colony, say that combining the schools would fit with a broader plan to concentrate limited resources on a smaller number of institutions.

“It would be tragic for Hong Kong to disrupt a university that is highest ranked in the region in its specialties, for reasons that are unsupported,” says Gary Biddle, associate dean of HKUST's School of Business and Management, which the Financial Times ranks sixth in the world among public universities. Many at HKUST suspect that the university is being targeted for a takeover because it's seen as a brash upstart that has bested its more venerable rivals in academic competition. Not so, says Ambrose King, CU's vice chancellor. “Some departments of the two universities are very complementary,” he says, “and if they work together they can achieve a very powerful position [in the academic world].”

Begun in 1991, HKUST is an attempt to bolster Hong Kong's historically weak system of higher education and minimal presence in research. Billed as the “Massachusetts Institute of Technology of Asia,” the university is supposed to help Hong Kong move away from trade and low-end manufacturing and into the emerging and more lucrative knowledge economy. Its modern campus, with dramatic buildings overlooking a scenic bay, has attracted ethnic Chinese scientists from around the world, who have earned international attention for their work on carbon nanotubes, semiconductor physics, and gene-chip technology. Its current president is Paul Chu, renowned for pioneering research on high-temperature superconductivity at the University of Houston.

But success doesn't guarantee autonomy. Last month the University Grants Committee (UGC), an advisory body that oversees higher education and research in Hong Kong, formed a special committee to weigh the pros and cons of a merger. Arthur Li, Hong Kong's secretary for education and manpower and the former vice chancellor of CU, was the first to float the idea publicly when he announced last October at a press conference that the government would support a merger of the two schools. (Vice chancellor is the top post at CU, the titular chancellor being Hong Kong Chief Executive Tung Chee Hwa.) Li says that the idea arose from long-running informal discussions among administrators at the two universities. “I don't think the government would be that stupid” to push through a merger without the support of both universities, says Li, a surgeon who rose through the CU medical ranks.

But that isn't the way HKUST administrators remember events. Chia-Wei Woo, a physicist and founding president who retired in mid-2001, recalls that Li raised the issue of a merger with a member of HKUST's university council in early 2001 but that the overture was rejected. Chu, who succeeded Woo, says that the idea of a merger was broached once during his presidency but “was nothing of any consequence.”

Once Li went public with the notion, however, both schools set up task forces to study it. At HKUST, a Committee of Concerned Faculty has become a vocal critic, and some accuse Li of using his government position to strengthen his alma mater at HKUST's expense. A poll by the committee found that 86% of 293 replying HKUST faculty members oppose a merger. Similar percentages answered “no” to the questions of whether size was a good way to achieve world-class status and whether university mergers work.

Opponents of a merger say that the schools have different missions and cultures (see above). Many HKUST faculty members feel that a merger would reduce their independence and weaken their ability to excel in carefully chosen niches. “From the beginning, our fairly unusual department has focused on condensed matter physics,” says Ping Sheng, head of HKUST's department of physics. Concentrating efforts in one specialty led to clear priorities in purchasing equipment, establishing research programs, and recruiting faculty. The result has been “work that people [in the worldwide physics community] know very well,” says Y. R. Shen, a materials scientist at the University of California, Berkeley, who helped set up the school's physics department.

The CU task force, in contrast, found potential advantages in merging, mainly because it would create a critical mass of students and faculty. It noted that dropping duplicate journal subscriptions, for example, would save money that could go toward additional titles or other library services. The combined university, it added, could also offer a wider range of courses without increasing the burden on faculty.

Joseph Sung, a CU professor of medicine, also predicts research synergies. HKUST's work in neuroscience, molecular biology, and Chinese medicine, for example, would be a natural match for CU's medical school and its affiliated hospital. “We could help move their drug theories into clinical trials,” he says.

Although academics at the two schools are divided over the question of a merger, they agree that government and community support for higher education is inadequate. HKUST's Biddle cites World Bank data indicating that only 27% of Hong Kong's graduating secondary school students pursue tertiary education, compared with 44% in Japan and Singapore, 56% in Taiwan, and 68% in South Korea. A ceiling on government support for university slots is the limiting factor. “Our big failure has been in not being able to convince business and political leaders of the value of greater funding for higher education and research,” says Woo.

The already tight funding situation is likely to get worse. University budgets face a 10% cut in the 3-year fiscal term beginning in mid-2004, although a grant-matching scheme will give them a chance of recovering some of the cuts. Opponents say that the shrinking budget is another reason to put off any merger. “Research makes clear that university mergers are costly and rarely successful,” says Biddle. But CU's Sung thinks that “a merger may be the best thing we can do to try to maintain the level of our programs.”

The UGC panel, composed of local and foreign academics and a handful of local business people, is expected to deliberate until January. It's not clear whether the committee will make a final decision or just clarify the pros and cons. “It's very much up to the universities to decide what they want to do,” says Li, although his position is clear: “It's obvious that if you want growth, one quick way of expansion is to share courses, form alliances, and ultimately merge.” For its part, HKUST's faculty members are hoping that an independent UGC panel will come out in favor of an independent HKUST.