# News this Week

Science  15 Jan 2010:
Vol. 327, Issue 5963, pp. 254
1. Virology

# An Indefatigable Debate Over Chronic Fatigue Syndrome

1. Sam Kean

Here we go again. The search for the cause of chronic fatigue syndrome, which just months ago seemed to be gaining traction, now seems likely to descend into the same confusion and acrimony that characterized it for years, as a supposed viral link to CFS published just last autumn might be unraveling.

Many patients with CFS—long-term fatigue and other ailments that have no known biological cause—report that their symptoms began after an acute viral infection, and scientists have tried many times, but never successfully, to pin CFS to viruses such as Epstein-Barr. Patients have faced skepticism for years over whether CFS is a “real” disease; a viral trigger could vindicate them and explain their nebulous symptoms.

That's why a paper published online 8 October 2009 in Science (http://www.sciencemag.org/cgi/content/abstract/1179052) caused such a stir. A U.S. team reported finding DNA traces of a virus, XMRV, in the blood cells of two-thirds of 101 patients with CFS, compared with 4% of 218 healthy controls. Strangely, XMRV, a rodent retrovirus, had previously been implicated in an aggressive prostate cancer. No one knows how XMRV might contribute to either or both diseases, but the authors argued that the link made some sense: XMRV ravishes natural killer blood cells, which attack both tumors and cells infected by viruses.

Other scientists thought the link dubious, criticizing the team, led by Vincent Lombardi and Judy Mikovits at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, for not explaining enough about the demographics of their patients or the procedures to prevent contamination (Science, 9 October 2009, p. 215). Several virologists around the world practically sprinted to their labs to redo the experiments, and the discovery that a clinic associated with some people at Whittemore was selling, among other CFS services, a $650 diagnostic test for XMRV made the issue more pressing. A U.K. team already exploring the XMRV–prostate cancer link won the race, submitting a paper to PLoS ONE challenging the claim on 1 December 2009. It was accepted for publication after 3 days of review. The British team, led by retrovirologist Myra McClure of Imperial College London, examined DNA from the blood of 186 CFS patients ranging in age from 19 to 70, with an average age of 40. Most were markedly unwell. McClure's team used a PCR machine—which copies and amplifies scraps of DNA—to search for two viral sequences, one from XMRV and the other from a closely related virus. They discovered nothing. At a press conference discussing the results, published online 6 January in PLoS ONE, McClure was blunt and confident: “If there was one copy of the virus in those samples, we would have detected it.” This null result prompts the question of what—if anything—was wrong with the original paper. The PLoS ONE authors seem to suggest that contamination was at fault, stating that they were careful to work in labs that had never handled XMRV and use PCR machines that analyze no mouse tissues. But McClure says her group merely wanted to make that explicit, not accuse anyone. The U.S. team followed the same procedures, retorts Lombardi, a biochemist. He also expressed bewilderment that the McClure group didn't search its CFS samples for the same DNA sequence as his team had, raising the possibility that they had different results because they searched for different things. The McClure team, however, looked for not only an XMRV sequence but also a sequence in a closely related virus, MLV. That MLV sequence, highly conserved among viruses of its class, would presumably have been found if XMRV was present, they said. One distinct possibility, says John Coffin, a microbiologist at Tufts University in Boston who studies retroviruses and wrote a separate analysis for Science when the original paper was published (http://www.sciencemag.org/cgi/content/short/1181349), is that both papers are right. He called the PLoS ONE paper too “preliminary” to settle the debate and said XMRV could show more genetic variety, and thus be harder to detect, than anyone assumed. It's also possible that distinct strains of XMRV appear in different parts of the world, as do the retroviruses HIV and HTLV (a leukemia virus). Intriguingly, although research teams in the United States have linked XMRV to prostate cancer, multiple teams in Germany and Ireland have failed to find a connection. Coffin says one more possibility, raised by many scientists, is that CFS is actually a suite of diseases that present the same symptoms and so might have many causes. Lombardi agrees. “It's naïve to think that everyone with chronic fatigue has the same etiology. There's probably going to be a subset of people with CFS that have XMRV, and it will probably end up being classified as XMRV-related CFS.” All of this leaves doctors and patients in a muddle. There's no doubt they're hungry for information. Out of curiosity, Lombardi did a Google search on “XMRV” the day before the Science paper hit and found about 22,500 hits. Three months later, there are 400,000. But some scientists, including Coffin and McClure, fear that the Viral Immune Pathology Diagnostics clinic (VIP Dx) took advantage of that hunger by offering the$650 diagnostic test for XMRV, 300 of which have been administered so far and which already has a 4 to 6 week backlog. “Leaving aside the issue of who's right and who's wrong,” says Coffin, “the original paper did not establish the virus [caused CFS] and didn't establish it as a viable marker.” So it's not clear what a patient or physician could do with a positive result. Steve Kaye, a colleague of McClure's at Imperial College London and a co-author of the PLoS ONE paper, noted with some alarm that the authors of the Science paper had speculated about treating XMRV with antiretroviral drugs, which can have harsh side effects.

However, VIP Dx developed its XMRV test only after a different company began offering one; VIP Dx officials saw their test as a more expert alternative. What's more, Lombardi—an unpaid consultant for VIP Dx who helped set up and manage the testing program—argues that the test is useful. Patients could in theory avoid infecting other people with XMRV and can have their diagnoses validated, if nothing else. His test results also bolster the science in the original paper; he says 36% of tests have detected XMRV, including a few from the United Kingdom. (Test proceeds roll back into research and development at Whittemore, which licenses the test to VIP Dx. VIP Dx has also received financial support from the Whittemore family in the past.)

To resolve the dispute, both sides say they are willing to work with the other and possibly test each other's samples. In the meantime, more papers exploring the link are slated to appear in the next few months, and each side says it knows of work supporting its results. All that suggests that the field will continue to churn. As McClure told Science, “we take no pleasure in finding colleagues wrong or dashing the hopes of patients, but it's imperative the truth gets out.”

2. Archaeology

# Neandertal Jewelry Shows Their Symbolic Smarts

1. Michael Balter

Neandertals had big brains and were skilled hunters, but their sites reveal few objets d'art. So some researchers have suggested that Neandertals weren't cognitively up to the job of producing art and symbols, although a growing number disagree. Now a handful of marine mollusk shells, possibly used as necklaces and paint cups, shows that Neandertals did express themselves symbolically, say the authors of a paper published online this week in the Proceedings of the National Academy of Sciences. They argue that the findings suggest that social and demographic factors, rather than cognitive differences, best explain why so-called modern behavior was relatively rare among Neandertals. The paper suggests that “Neandertals too had such [symbolic] capacities,” says archaeologist John Speth of the University of Michigan, Ann Arbor.

The shells were found in the Aviones cave and the Antón rock shelter in southeast Spain, both identified as Neandertal sites from their ages and stone tools. Radiocarbon dating of shells at Aviones puts the Neandertal occupation there at between 45,000 and 50,000 years ago—before modern humans entered the area—and charcoal at Antón came out at between 37,000 and 43,000 years old.

An international team led by archaeologist Joãao Zilhão of the University of Bristol in the United Kingdom examined three cockleshells from Aviones that were perforated near their hinges and were found alongside lumps of yellow and red pigments. A fourth, unperforated, thorny oyster shell contained residues of red and black pigments and was perhaps used as a paint container, the team says. At Antón, a perforated scallop shell was painted on its external side with a blend of orange pigments, perhaps to make the shell's outside resemble its naturally red inside surface. Zilhão's team concludes that although the perforations were not humanmade, Neandertals selected shells with holes of 4.5 to 6.5 millimeters, ideal for stringing as ornaments.

“The authors make a good case” that the shells and pigments were used in “an aesthetic and presumably symbolic” way, says archaeologist Erella Hovers of The Hebrew University of Jerusalem. Hovers cites similar finds from Israel's Qafzeh Cave, which was occupied by modern humans as early as 92,000 years ago and where perforated cockleshells and red ochre pigments have been widely accepted as evidence of modern human behavior.

Although signs of Neandertal symbolism are rare, ornaments become more common at Neandertal sites when modern humans arrive in Europe about 40,000 years ago, leading some to argue that the Neandertals copied modern human symbolic behavior rather than inventing it themselves.

But as the older perforated shells suggest, that does not mean Neandertals were not capable of creating symbols, Speth says. “The assumption [has been] that when you first see symbolic media such as ornaments, that's the first time humans had the mental wherewithal to make them. By that logic, humans lacked the cognitive capacities necessary to invent the atomic bomb until World War II. That is obviously nonsense.”

So why are ornaments plentiful at modern human sites and rare at Neandertal ones? Social and demographic factors, Zilhão and others say. In this view the Neandertals, with relatively low population densities, may have lacked the widespread social networks that required symbolic communication within and among population groups. Early humans engaged in symbolic behavior only “when it was advantageous,” says Hovers, and when “populations were stable enough over time to keep these canons and traditions alive.”

# NIST Grants Help Schools Build for Tomorrow's Research

1. Jeffrey Mervis

Habib Dagher, a structural engineer at the University of Maine, Orono, wants to replace the heating oil that warms most Maine homes with a cheaper, renewable fuel—electricity generated by wind turbines 30 km offshore in the Gulf of Maine. To withstand the punishing ocean conditions, the 100-meter turbines would be made from a polymer composite, stiffened by cellulose fibers, created by researchers at the university's Advanced Structures and Composites Center he directs. But researchers need more lab space to design, prototype, and test the unique building material.

Fortunately for the center, Dagher not only thinks green but also knows where to find the green. Last week, the center learned it was one of 12 winners in the second and final round of a $180 million competitive construction grants program at the National Institute of Standards and Technology (NIST). The$12.4 million NIST grant, combined with $5 million from the state of Maine, will allow Dagher to build the Advanced Nanocomposites in Renewable Energy Laboratory at the center. The center has received a$5 million earmark inserted into the Department of Energy's 2010 budget by the state's congressional delegation, and it's part of a consortium that won a $7 million grant in October from DOE to test the offshore wind turbines. In addition, Dagher hopes that Maine voters will approve a$6 million bond issue this summer to equip the new lab.

The NIST program is a small component of the $787 billion stimulus package designed to revive the U.S. economy (Science, 27 November 2009, p. 1176). Aimed at funding “shovel-ready” projects such as the nanocomposites lab, the grants address a gap in the federal government's academic research portfolio, which traditionally has favored supporting scientists over bricks and mortar. “This is the hardest type of money to get,” says Dagher. “And without the NIST grant, the whole project would have been slowed down considerably.” The NIST competition attracted 167 proposals from universities clamoring for help in funding new construction during tough economic times. (A smaller competition in 2008 chose three winners from 93 proposals, and in July, NIST gave$55 million in stimulus money to four institutions that had just missed the cut.) The new facilities are intended to enhance the mission of either NIST or the National Oceanic and Atmospheric Administration (NOAA), its sister agency within the Commerce Department. The federal dollars leverage money already on the table: The $123 million allocated last week will make possible more than$250 million in new laboratory construction.

The University of Pittsburgh in Pennsylvania, for example, had already committed $12.7 million toward 13 new physics laboratories, part of a 12-year strategic plan, and the$15 million NIST grant gives it a green light to proceed. “Without this grant, I don't know how many years it would have taken us” to complete the project, says N. John Cooper, dean of arts and sciences. Despite an overall 5% spending cut this year that has slowed hiring, Cooper says the NIST grant “positions us to be more competitive when the upturn comes.”

For the Woods Hole Oceanographic Institution (WHOI) in Massachusetts, an $8.1 million award for a laboratory for ocean sensors and observing systems will help it do a better job as a major contractor for a project supported by the National Science Foundation (NSF). The Ocean Observatories Initiative (OOI) will deploy networks of sensors to collect long-term data from the sea floor (Science, 16 November 2007, p. 1056), and Laurence Madin, WHOI's executive vice president and director of research, explains that “once we got the NSF award, we realized that we needed a special facility to do everything that OOI would require.” Although WHOI has received NOAA funding for many years, says Madin, “this is actually our first NIST award.” Some of the NIST construction funding will help improve construction practices themselves. An$11.8 million NIST grant to build the Center for High-Performance Buildings will allow Purdue University scientists to reconfigure office space to maximize comfort, safety, and energy efficiency, says James Braun, a professor of mechanical engineering. The new lab space, he adds, may even boost the team's application, now pending at NSF, for an Engineering Research Center on the topic.

4. Chemistry

# Catalyst Offers New Hope for Capturing CO2 on the Cheap

1. Robert F. Service

If international agreements can't slash carbon dioxide emissions fast enough to tame global warming, how about sucking it out of the air? Technology using chemicals that bind CO2 already exists, but it's so expensive that using it on a large scale could increase energy demand—and the cost of energy—by at least one-third.

On page 313, however, researchers in the Netherlands report a new copper-based catalyst that can capture CO2, convert it to a different form, and then release it with a small fraction of the energy other techniques require. “This is an important fundamental advance,” says William Tolman, an inorganic chemist at the University of Minnesota, Twin Cities. “But there's a long way to go before you could turn it into a catalytic process” for reducing atmospheric CO2, he adds.

The new method targets the step that so far has proved to be the Achilles' heel of air capture: prying the trapped CO2 loose so the capture compound can be used again. Various processes do that through heat, electricity, or changes in air pressure, all of which require a lot of energy.

Researchers led by Elisabeth Bouwman, a chemist at Leiden University in the Netherlands, hit on a possible way to lower the penalty while working on a very different problem: designing small metal-containing organic compounds to mimic the behavior of an enzyme called superoxide dismutase. In living organisms, the enzyme neutralizes superoxide, a reactive form of oxygen that is generated inside cells and that can damage DNA.

One copper-containing candidate compound surprised them. Instead of oxygen, it bound carbon dioxide by stitching two CO2 molecules together into a compound known as oxalate. X-ray crystallography showed that two pairs of the carbon complexes join together in a single unit to knit four CO2 molecules into two oxalates (see figure). Kenneth Karlin, an inorganic chemist at Johns Hopkins University in Baltimore, Maryland, who has worked on related compounds, says the new catalyst's ability to selectively bind CO2 and cause it to react is impressive. “This is amazing,” he says.

Bouwman's group also worked out a way to regenerate the starting copper complex so that it could be used again. They simply added a lithium salt to their solution. The lithium swipes the oxalate from the copper complex, creating lithium oxalate. Then applying a very small voltage of −0.03 volts to the copper complex restores it to its original form. Adding an electron directly to CO2—the first step in converting CO2 into more complex, and useful, molecules—would require −2 volts, Bouwman says.

Bouwman acknowledges that the new CO2 catalyst isn't yet ready to become a bona fide air-capture technology. It works too slowly, and the lithium salt is too expensive. Bouwman says transferring the oxalate to a cheaper chemical shouldn't be difficult, and her group is already working to improve the catalyst's reaction rate.

Ultimately, if a CO2 air-capture technology is to be realistic on a large scale, the cost and energy requirements must come down, says Andrew Dessler, a climate scientist at Texas A&M University in College Station. “Air capture could be viable, but not unless research like this gets the energy requirement way down from where we are now,” Dessler says. “So this kind of research is very exciting.”

5. ScienceNOW.org

# From Science's Online Daily News Site

Egyptian Eyeliner May Have Warded Off Disease Clearly, ancient Egyptians didn't get the memo about lead poisoning. Their eye makeup was full of the stuff. Although today we know that lead can cause brain damage and miscarriages, the Egyptians believed that lead-based cosmetics protected against eye diseases. Now, new research suggests that they may have been on to something.

Why Light Makes Migraines Worse Migraine sufferers often retreat to a dark room or pull the shades down. Any light just makes the searing pain worse. Now, scientists think they know why—thanks to some help from blind volunteers.

Bering Strait's Ups and Downs Alter Climate The Bering Strait, the 80-kilometer-wide stretch of ocean between Russia and Alaska, can strongly influence the climate of the entire Northern Hemisphere, researchers have calculated. The findings answer a question that has dogged scientists for the past decade, and they demonstrate how seemingly slight changes in certain factors can impact global climate.

The Spiky Penis Gets the Girl When it came to insect penises, Charles Darwin had it right. The famed naturalist suspected that insect genitalia, which are frequently festooned with bizarre combinations of hooks, spines, and knobs, essentially functioned like peacock tails. That is, they helped males beat out their rivals for females. Now, researchers have confirmed this hypothesis by zapping fly penises with a laser.

6. Astronomy

# Oldest Galaxies Show Stars Came Together in a Hurry

1. Yudhijit Bhattacharjee

Sifting through images taken by the newly refurbished Hubble Space Telescope, astronomers have spotted five galaxies that date back to a mere 600 million years after the big bang—the earliest galaxies found so far by 200 million years. The discoveries take researchers close to the primordial stage of cosmic evolution, when the first galaxies were taking shape.

Astronomers have already learned a few things about the newly discovered galaxies. For one, they are tiny compared with contemporary galaxies—barely 5% the size of the Milky Way and less than 1% its mass. “These are the seeds of the great galaxies of today,” says Garth Illingworth of the University of California, Santa Cruz, who presented the findings at the American Astronomical Society meeting in Washington, D.C., last week.* Illingworth led the survey team that took the new images using Wide Field Camera 3, one of two new instruments mounted on Hubble in a servicing mission last year.

Another striking fact about the galaxies is that they are populated by stars that had already been burning for 300 million years. That pushes back the birth of the earliest stars of the universe to within a few hundred million years of the big bang—a blink of an eye in astronomical time.

Volker Bromm, an astrophysicist at the University of Texas, Austin, says the new galaxies “clearly demonstrate the hierarchical nature of structure formation—small objects formed first—and provide interesting constraints for early star formation.”

Theorists think the very first stars, known as Population III stars, were massive stellar objects made only of hydrogen and helium and didn't live for very long. The first normal low-mass stars—called Population II and I stars—could form only after Population III stars had exploded as supernova and enriched the universe with heavier elements forged in the process.

The imaging of the new galaxies, with the discovery of Population I and II stars within them, implies that “the transition in cosmic star formation mode, from Pop III to Pop I and II, took place quickly, in dark-matter systems that were even smaller” than the refurbished Hubble can see, Bromm says. He adds that the “true moment of first light remains elusive, and its discovery has to await the James Webb Space Telescope”—planned for launch in 2014.

In addition to Illingworth's team, four research groups have reported similar findings from their analyses of the new Hubble data.

• * 215th AAS Meeting, Washington, D.C., 3–7 January.

7. Astronomy

# Inventory Asks: Where Is All the Non-Dark Matter Hiding?

1. Yudhijit Bhattacharjee

Astrophysicists know that 83% of the matter in the universe is dark matter—invisible stuff as yet undetected. The other 17% is detectable “baryonic matter,” the atoms and ions that make up stars, planets, dust, and gas. To astronomers' surprise, the ratio of baryonic matter to dark matter seems to vary from galaxy to galaxy like the ratio of chocolate chips to dough in different batches of home-baked cookies. Now, a team led by Stacy McGaugh at the University of Maryland, College Park, has determined that the proportion varies by scale: The largest galaxies have the highest percentage of baryonic matter, although not quite 17%; whereas the smallest galaxies have less than 1%.

McGaugh and colleagues compiled the ratios for more than 100 galaxies ranging from supermassive ones to dwarfs. Researchers infer the amount of dark matter in a galaxy from the motion of its stars. They estimate its baryonic mass from the amount of light the galaxy emits, which can be converted to the total mass of its stars, and a measure of atomic hydrogen in the galaxy, which provides an estimate of the interstellar gas.

“What we find is that there is a very systematic variation in the ratio with scale,” says McGaugh, who presented the findings at the American Astronomical Society meeting in Washington, D.C., last week.* “When you go to the very large galaxies, the baryonic matter can be as much as 14%. As you go down in size, you see that galaxies fall short of the cosmic fraction [17:83] by an ever-increasing amount.” In galaxies the size of the Milky Way, “all the stars and gas add up to only a third of the baryonic matter you would expect,” which is about 5%. And in the smallest dwarfs, baryonic matter is a hundredth of what's expected—as minuscule as 0.2%. “These are very interesting results” that quantify the “missing baryonic matter problem,” says Joel Bregman, an astronomer at the University of Michigan, Ann Arbor.

Where is all the missing baryonic matter lurking? One hypothesis is that its particles are interspersed within the galaxy's dark matter halo in the form of undetectable hot gas. Another is that supernova explosions have blown it into intergalactic space. This second idea would square with McGaugh's findings: Large galaxies, with stronger gravitational pulls, would be able to retain more of their baryonic matter, whereas smaller galaxies would let more escape. But so far, McGaugh says, that explanation is just one of several lines of speculation.

• * 215th AAS Meeting, Washington, D.C., 3–7 January.

8. Publishing

1. Jocelyn Kaiser

Should all papers that result from U.S. taxpayer–funded research be made freely available? The White House science office likes the idea and has asked for input on whether many federal agencies should formally adopt it. So-called open access advocates are enthusiastic in comments submitted to a White House forum, but some scientific societies remain wary, fearing that a too-broad public-access policy could kill journal subscriptions.

Both sides agree that the White House appears to be moving toward a plan. “They're focusing not on should we do this but how would we do this,” says Heather Joseph, executive director of the Scholarly Publishing and Academic Resources Coalition, a librarian group and open-access proponent.

The push for mandatory release of research papers started 2 years ago at the National Institutes of Health, which required that grantees send copies of their peer-reviewed, accepted papers to the agency. NIH posts the final manuscripts or published papers in its free PubMedCentral archive; release can be delayed on request up to 12 months after publication. The objective has been to give patients and the public broader access to research results. Despite grumbling from publishers, NIH says the policy is working smoothly.

Last month, as part of President Barack Obama's “open government” activities, the Office of Science and Technology Policy (OSTP) launched an online discussion about whether the NIH model should be expanded to other agencies. The OSTP forum asks nine questions, including how to ensure that authors comply.

About 400 comments have been submitted so far from scores of individual scientists, librarians, publishers, and others. The majority support broadening public access, says OSTP Assistant Director of Life Sciences Diane DiEuliis, a neuroscientist on detail from NIH. “There was a fair consensus on the general issue,” she told Science by e-mail, as well as on other questions, such as “embargo times”: how long an author and journal can keep a paper under private control. Many suggested using the current NIH embargo—12 months—and preferred central repositories like PubMedCentral rather than university archives.

But even a 12-month delay worries some nonprofit scientific publishers. For example, mineralogists and anthropologists argued that their papers—unlike those in biomedical research—may have a very long “half life” and that releasing the full text on the Internet could cause journals to lose subscribers. Katherine McCarter of the Ecological Society of America, which has not yet submitted comments, says that for ecology journals, “even a 1-year delay could be a real disincentive to buy a subscription.”

The cost of producing a single paper can run significantly higher in social sciences because papers need more space and require a “more robust peer-review process,” argues William E. Davis III, executive director of the American Anthropological Association. His letter warns that mandatory release of such papers “could well result in the demise of the very journals that … advocates seek to make more freely available.”

Despite such concerns, OSTP seems to be moving inexorably toward a general open-access policy. DiEuliis says OSTP will sort through all comments (the deadline has been extended until 21 January) and send suggestions to an interagency working group. This panel will also consider a report due this week from a group of publishers and other stakeholders that OSTP and the House Science Committee convened last June. One possibility, DiEuliis says, is that OSTP could draft an executive order or memo that would set out “minimum standards” but “give agencies flexibility to create custom plans.”

9. ScienceInsider

# From the Science Policy Blog

The director of the Royal Institution of Great Britain, the London-based science institution, has been dismissed and her position eliminated in what appears to be a cost-saving move. But neuroscientist Susan Greenfield, who has held the job for more than 10 years, says she is considering a legal challenge, possibly including discrimination charges, to her dismissal.

The White House has released a much-awaited report on strengthening U.S. biosecurity rules. Instead of applying the same security standards to all so-called select agents, the report recommends a stratified system that would toughen security for the most hazardous agents and ease rules for less dangerous ones. That's the approach, favored by many scientists, that lawmakers envisioned in a bill introduced in the U.S. Senate last fall.

The U.K. House of Lords Science and Technology Committee says there's no evidence that foods containing nanometer-scale particles—dubbed nanofoods—constitute a danger to consumers. In the new report, the committee said that nanofoods nonetheless deserve scrutiny, citing “huge gaps” in current knowledge. In addition, “we urge the European Commission to clarify the definition of a nanoparticle in the context of food,” said committee chair John Krebs.

Senior Democratic lawmaker Byron Dorgan (D–SD) has decided not to seek reelection this year. Insider analyzed his record as “Cardinal” of the Senate subcommittee that controls Department of Energy funding. Some lobbyists have claimed that Dorgan has emphasized nuclear waste cleanup or water projects at the expense of basic physical science research, but under his 3-year tenure, research and development spending at DOE has risen. The subcommittee's staff clerk, who wields considerable influence, is appointed by the Appropriations Committee chair and is likely to be staying on.

For the full postings and more, go to blogs.sciencemag.org/scienceinsider.

10. Entomology

# The Little Wasp That Could

1. Elizabeth Pennisi

The sequencing of the genome of a parasitoid wasp promises to bring wider recognition to these tiny, underappreciated insects that play a crucial role in natural ecosystems and in agriculture.

The British geneticist J. B. S. Haldane once famously quipped that God seems to have had an inordinate fondness for beetles, given their numbers and diversity. If so, then he must have been besotted by parasitoid wasps. Tinkerbells of the animal kingdom, many of these insects are no bigger than fleas, yet they may well outnumber beetles.

Unlike beetles, however, parasitoid wasps aren't exactly charismatic. “You get one in your eye and pull it out with your finger and think it's a piece of dust,” says Daniel Janzen, an ecologist at the University of Pennsylvania. “There's millions of individuals out there, and you don't even know they exist.” Yet these inconspicuous insects play a crucial role in natural ecosystems and in agriculture. They destroy the eggs, larvae, or cocoons of countless species of insects and arthropods, sometimes with hugely beneficial effects: The U.S. Department of Agriculture (USDA) estimates that parasitic wasps save the United States at least $20 billion annually by controlling invasive species. “I think very few people realize what a force they are in the biology of our planet,” says Michael Strand, an entomologist at the University of Georgia, Athens. Scientists, on the other hand, have long appreciated their attributes. The wasps' unusual genetic makeup has made one a lab favorite—“yeast with wings,” says John Werren, an evolutionary geneticist at the University of Rochester in New York state. Entomologists are fascinated by the wasps' sometimes bizarre life histories, and ecologists have recently come to recognize their astonishing diversity. Now, their scientific value is about to increase: On page 343 of this issue, a 157-person consortium presents the genome sequence of three parasitoid wasps, members of the genus Nasonia, which attack flies. The genome “not only solidifies Nasonia's standing as the lead model organism for the vast insect order Hymenoptera but [also] brings it on par with traditional heavyweights such as C. elegans and Drosophila,” says William Sullivan of the University of California (UC), Santa Cruz. ## Beetles, stand aside! Janzen first started noticing parasitoid wasps when they played havoc with his studies of Lepidoptera in Costa Rica. Since the early 1980s, he has been collecting caterpillars and raising them to adulthood to see which butterfly or moth they belonged to. All too often the caterpillar would turn to mush, and out of it would emerge parasitoid wasp larvae. But, fanatic collector that he was, Janzen saved these tiny insects and documented their food source. Each year, he would take them to a wasp expert for identification. Two decades later, his inventory totals about 20,000 wasps, and his awareness of how common they are has grown exponentially. They don't just prey on moth and butterfly caterpillars. Adult females lay eggs in or on the eggs, larvae, or pupae of many insects and arthropods, on which the wasp larvae feed. Some can lay 200 eggs in one caterpillar; others inject a single egg that divides many times to give rise to separate, cloned larvae. Sometimes, the larval wasps can sit quietly in the caterpillar, evading the immune system, until their host has fattened up, then they eat it from the inside out in a matter of days. Several species treat their insect host as a nest and set up a social hierarchy to defend it. All nestmates are clones, but only some developing embryos inherit germ cells. The sterile clones become soldiers and help protect larvae destined to become reproductive adults from other parasites, says Strand. Parasitoid wasps have intimate connections with microbial partners as well. Many wasps are infected with the bacterium Wolbachia, which can skew the sex ratio of offspring. Others carry a “male-killing” microbe that eliminates males in a developing brood. Some have even co-evolved with a virus that a female injects into a caterpillar along with an egg; the virus disarms the caterpillar's immune system. These viruses are now part of the wasps' DNA. “The diversity of life histories of [these insects] is hair-raising,” says Strand. These tiny wasps may have diverse lifestyles, but many tend to look alike. Even experts have trouble identifying which species individuals belong to. So when DNA bar-coding was just getting started and its proponents were looking for groups of animals on which to try this short-hand species-identification tool, Janzen volunteered his collections. There turned out to be “a lot more species out there than we realized,” says Janzen. A 2008 DNA bar-coding analysis of 2597 parasitoid wasps from his collection turned up 313 species, not the 171 researchers had previously thought. M. Alex Smith of the University of Guelph in Canada and Josephine Rodriguez of UC Santa Barbara discovered that what was believed to be a single species—a 2-millimeter-long wasp called Apanteles leucostigmus with a black body and a white rhomboid patch on its wing—proved to be 36. And there were many more examples of previously unrecognized species, Janzen, Rodriguez, Smith, and their colleagues reported in the 26 August 2008 issue of the Proceedings of the National Academy of Sciences. Between 50,000 and 60,000 different species of parasitoid wasps have now been described. But systematists think that's just the tip of the iceberg. “It's one of the groups that has been understudied historically,” says James Whitfield, a parasitic wasp systematist at the University of Illinois, Urbana-Champaign (UIUC), who works with Janzen. When researchers sampling tropical insects use foggers to down all the insects in a tree canopy, sometimes more parasitoid wasps come raining down than even beetles, and “the percentage that are new is just really high,” says Whitfield. The group he studies contains many species that can't be told apart except through molecular studies. “There's a really compelling argument that these parasitoid wasps may be more diverse than beetles,” says Strand. “Virtually every arthropod on Earth is attacked by one or more of these parasitoid wasps.” ## Biocontrol agents Some researchers think this diversity has arisen in part because these wasps are such picky eaters. A few are generalists, laying eggs in a variety of pupae or caterpillars. But many attack only one particular prey; Janzen's records show, for example, that more than 90% of the wasps parasitize only one or two species of caterpillar. “These parasitoids are vastly more host-specific than anyone thought they were,” says Janzen. This specificity not only underlies the diversity of wasp species—the wasps are as diverse as the species they invade—but also makes the insects appealing for biological pest control. “The goal is host-specific natural enemies,” says Kevin Hackett, an entomologist with the USDA Agricultural Research Service in Beltsville, Maryland. Indeed, one of these little wasps saved the African cassava crop in the 1980s. Cassava comes from South America, but in the past 400 years, it has become a crucial staple for millions of Africans, particularly those living on marginal land where few other crops thrive. In the early 1970s, the cassava mealybug arrived from South America in some planting materials and quickly spread. Within a decade, the insect was causing crop losses of up to 80%. Mealybugs are relatively rare on cassava in South America. The reason, scientists discovered, is the parasitoid wasp Apoanagyrus lopezi, which parasitizes the bug. After studying the wasp to assure themselves that it would not become a pest itself in Africa, researchers reared large numbers of the wasp in Benin, then introduced it into 30 African countries. The mealybug is no longer a problem in Africa. Parasitic wasps have come to the rescue elsewhere, but finding the right wasp for the job hasn't always been easy. The wasp must come from a climate similar to the one in which it will be working, it must be released at the right time of the year, and researchers must learn enough about the species to raise and feed a few thousand for release. But the potential need is high, says Hackett: One new invasive species arrives in the United States every 6 weeks, on average. Take the case of the cabbage butterfly (Pieris rapae), which invaded North America in the late 1800s. More than a century ago, Charles Riley, the chief entomologist at USDA, turned his sights on this butterfly, whose caterpillar munched its way through kale and cabbage crops. He imported a parasitoid wasp from England in 1881, but “they got the wrong wasp,” says Roy Van Driesche, an entomologist at the University of Massachusetts, Amherst. By 1884, a population had been established near Washington, D.C., but it was never very effective; neither was a wasp brought in from Yugoslavia in the 1970s. Only now, with the spread of a wasp imported from Beijing in the 1980s, is the cabbage butterfly being thwarted, says Van Driesche, who orchestrated the new introduction. The Chinese wasp hails from a similar climate, and it kills the caterpillar early in its life, before it has a chance to do much damage. Despite their promise as biological control agents, parasitoid wasps have some commercial drawbacks. Private companies are not much interested in them because once the wasps are established, nature takes over and sales dry up. And concerns about the possible risks of releasing introduced species into the wild have also dampened enthusiasm for the technique. ## Six-legged lab rat Within the lab, however, interest in parasitoid wasps has blossomed. “They provide excellent model organisms to explore a broad variety of questions in ecology and evolution,” says Charles Godfray of the University of Oxford in the United Kingdom. Others are keen to use them to study complex traits such as longevity, host preference, or female mate choice and to investigate the mechanisms of speciation. One wasp in particular is emerging as the lab rat among parasitoids, a fly hunter called Nasonia vitripennis. This wasp is easy to raise in the lab, has a short life cycle, and can interbreed with several closely related species if treated with antibiotics. (Otherwise, a Wolbachia infection makes the species incompatible.) And now N. vitripennis and its two closest relatives have joined the elite ranks of organisms whose genomes have been sequenced. “This wasp genome is very exciting,” says Hackett. In addition to helping scientists take advantage of Nasonia as a model system, it “will serve as a genetic resource for understanding other parasitoids,” he adds. Moreover, the publication of genomes of two closely related species, with a third on the way, “gives a real insight into how speciation occurred,” says Godfray. Werren and Stephen Richards of the Baylor College of Medicine in Houston, Texas, spearheaded the Nasonia genome project. Werren has long pushed to expand this insect's use in genetic and behavioral studies. Male wasps develop from unfertilized eggs and thus have a single copy of each chromosome, which simplifies certain genetic analyses: In experiments that generate mutants, any altered genes become readily apparent because there isn't a second copy to mask an effect. Moreover, it's easier to track a gene down and to detect interactions among genes in these so-called haploid organisms. N. vitripennis parasitizes larvae of house flies and other filth flies and is not too picky about its hosts. But its sibling species attack only blow flies found in bird nests. Cross-breeding studies have led Werren and post-doc Christopher Desjardins to a region of the genome responsible for host preference, and with further work, they hope to pin down the gene and figure out what it does. Such progress will promote a better understanding of speciation and can help entomologists figure out how to manipulate the genomes of parasitoids to improve their ability as biological control agents, says Werren. These wasps may prove useful in biomedicine as well. They produce venom that causes temporary paralysis and alters other physiological properties. When researchers recently combined a computer search of the newly sequenced Nasonia genome with a sophisticated mass-spectrometry analysis of the wasp's venom, they turned up 79 constituent proteins. Half the proteins were not previously associated with venom, including 23 that were unlike any seen before, Dirk de Graaf of Ghent University in Belgium and his colleagues will report in an upcoming issue of Insect Molecular Biology. “There is great potential that new drugs could emerge from the venom repertoire of parasitoids,” says Werren. These first genome comparisons also hint at what may underlie parasitoid wasp diversity. Not only are the venoms evolving very quickly and enabling the wasps to adapt quickly to new hosts, but mitochondrial genes are changing in double time. Drosophila mitochondria genes evolve about seven times faster than do genes in the nucleus; Nasonia's mitochondrial genes are evolving at least 35 times faster. That means nuclear genes for proteins that work in the mitochondria in one population of wasps very quickly become incompatible with another population's mitochondria, setting the stage for a species split. In addition to teaching researchers more about parasitoid wasps, the Nasonia genome “can play a crucial role in sharpening our insights” into the molecular basis of social life, says Gene Robinson, an entomologist at UIUC. It can begin to reveal which genes are common to all ants, bees, and wasps and which are specific to social insects. There is much more to be learned from this insect and its genome. It has 450 genes in common with humans that are not also found in fruit flies, including the full set of genes needed for methylation, a process involved in turning genes off semipermanently. “This species is no longer a ‘weird’ species with interesting features,” says Claude Desplan, a developmental geneticist at New York University in New York City. “It has graduated to be of help to address questions that cannot be investigated that easily in flies.” 11. Fisheries # Fishing for Gold in The Last Frontier State 1. Sam Kean A proposed mine at a gargantuan gold and copper deposit leaves some Alaskans fearful that they must choose between two great loves: salmon and mining. Tiffany's tastes are decidedly caviar, but the jewelry company has devoted itself lately to saving a less chichi seafood: sockeye salmon. Two years ago, Tiffany & Co. pledged never to buy gold from a gargantuan mine proposed for several dozen kilometers northeast of Bristol Bay, Alaska, a prolific salmon habitat. Since then, Tiffany has helped recruit a dozen other major jewelers to the preemptive boycott—some prestigious (Helzberg Diamonds), some less so (Sears, Walmart)—and continues to apply pressure. In October 2009, it took out a full-page, cyan-colored ad in the trade magazine National Jeweler, pleading that the “threat” to Bristol Bay “rises above all our immediate financial self-interests.” The jewelers' boycott is the most public skirmish in the touchy fight over the proposed Pebble Mine. In some ways, the fight feels familiar: Environmentalists see doomsday, whereas mining companies promise jobs and tax revenue. In other ways, this clash is atypical. Joining environmentalists are their sometime foes, fisheries, whose work buoys up much of Bristol Bay's economy. As a result, many people paint Pebble Mine as pitting two moneyed industries, mines and fisheries, against each other. And although people oppose the mine for other reasons, including a desire to shield other flora and fauna, salmon earn the most sympathy. In another twist, it's not clear how much the mine would threaten the 40 million salmon in the bay. Foes and proponents agree that the mine, as planned, would disturb less productive salmon habitats there. But scientists are amassing evidence that the unproductive habitats of today may be vital for a robust salmon population tomorrow. By mucking around in ancient mud, they have charted salmon populations over hundreds, even thousands of years. They've discovered that somewhat barren streams and lakes were wildly productive once, and populations in each habitat wax and wane naturally with shifts in climate. So, as a precautionary measure and to ensure that Alaska has fish to fish in the future, scientists contend that the state must preserve its variety of habitats—by killing Pebble. The Pebble Partnership—a joint venture of the mining companies Anglo American US LLC and Northern Dynasty Minerals—has said, many times, that it will proceed only if the project results in “zero loss” to fisheries, says Ken Taylor, head of the partnership's eight-person,$100 million (so far) environmental-assessment project. Taylor argues that giant mines and fisheries can co-exist.

Pebble officials also stress that they are merely exploring the site and have no firm plans. In fact, given the fickleness of Alaskan politics, it's not clear whether the mine will ever open. Pebble needs to secure state air and water permits, among others, and submit an environmental impact statement that the federal government will spend years scrutinizing. Tom Crafford, coordinator for large mines at the Alaska Department of Natural Resources, says Pebble would not crush its first rock until 2014, and that's if everything goes smoothly—if permits sail through, and court challenges end quickly. When Crafford mentions even that date, he chuckles, hard: “The likelihood of Pebble going smoothly is pretty minimal.”

## Mother lodes

The 3-km by 4-km Pebble deposit sits below marshy tan tundra, an expanse broken by mountains and veins of streams. Pebble West, 3.7 trillion kg of minerals, was discovered in 1988. Its ore was marginal, mostly low grade. Near the end of the survey, in 2005, engineers drilled a few last holes on the eastern edge. They hit the mother lode: Pebble East, an additional 3.1 trillion kg of higher-grade ore interred beneath a 1-km wedge of volcanic rock.

With that discovery, Pebble became a national environmental issue. The tiff with Tiffany focused attention on gold, but the Pebble deposit is largely copper—33 billion kg compared with 2.9 million kg (94 million oz.) of gold. (There's also 2.2 billion kg of molybdenum.) Metal markets can swing manically, but at today's healthy prices (gold at $1100 an oz.; copper at$7 per kg), the total deposit could be worth some \$370 billion.

Most people surmise that Pebble East would be a subterranean “cave” dig that would require moving 4 trillion kg of rock. Pebble West, likely a strip mine, would remove 4 trillion kg more from an open pit. (Foes of the mine claim the pit would stretch 3 km across and 600 m deep. Taylor says it would be much smaller.) Pebble would have to build its own power supply, as well as a 160-km service road to a Pacific Ocean port in a region not conducive to ground transport—no road exists to Anchorage 330 km away. Pebble must also accommodate 1000 or so on-site employees for up to 80 years.

Some scientists fear that those mining jobs, coveted by some locals, would undermine jobs in fishing. To scrub its low-grade ore, Pebble would require massive amounts of water, and as Crafford recognizes, “For mining projects, water, and water quality, and the protection of water quality, are the name of the game.” With the identity of the region tied up with salmon, he adds, “Pebble will be under an unprecedented microscope.”

To outsiders, the names of local waterways blur together in a series of gutturals: Ugashik, Egegik, Naknek, Kvichak. To salmon, each “run” is a unique ecosystem, as distinct as a city. Salmon spend their adult lives at sea but spawn—mate and lay eggs in gravel beds—in fresh water, a biological quirk that requires them to thrash upstream for sometimes hundreds of kilometers. And salmon are homebodies; they spawn in the waterway where they were born, so depleting a run can doom a population.

Preliminary permit applications suggest that Pebble would draw at least 76 million liters of water (estimates by opposition groups range up to 265 million) per day from the Koktuli and Talarik rivers, which drain into other rivers and lakes and then Bristol Bay. Pebble would also likely discharge processed water into streams—a prospect that worries environmentalists, who fear that even clean discharge could alter a habitat's temperature or salinity or sediment composition, preventing adults from reaching spawning sites or retarding the growth of juveniles. And unfortunately, metal mines don't have a history of clean living. Again, Pebble has no firm plans, but many gold mines use cyanide for extraction; ground-up waste rock could also release sulfides, rendering water more acidic. Some evidence suggests that aqueous copper—at concentrations below Alaska's legal limit—interferes with the way salmon navigate and detect predators and disrupts their food chain, although ecologists also admit that the harm, if any, is impossible to predict because natural processes often mitigate the effects of copper.

Scientists also worry about pollutants leaking horizontally through the wet tundra, because Pebble would straddle two watersheds with complex hydrology, says Sarah O'Neal, a population biologist at State of the Salmon, a Portland, Oregon, environmental group. “It's really hard to tell where the water's going there, even the surface water. It can cross watershed boundaries, and you can find any potential contaminants across any watershed.” It's therefore difficult to gauge which habitats are at risk, she says—and there are innumerable habitats: “Even the teeniest tiniest places, above disconnected channels, there are still fish in those little ponds.”

## Biocomplexity

Teeny-tiny ponds and creeks obviously don't supply millions of salmon and other fish, like trout, for Bristol Bay, but they're not irrelevant in the long term, say fishery scientists Daniel Schindler and Ray Hilborn, part of a University of Washington, Seattle, team studying the issue in Alaska with support from federal agencies and the Moore and Pew foundations. (A small percentage of support also comes from fisheries groups.) Hilborn estimates that the mine could threaten four or five of 15 distinct stocks of sockeye salmon, the most economically important species. Those four stocks account for 20% of the sockeye population now, “but at some times [those stocks] would have accounted for 80% of the production,” he says. In different eras, “there's an enormous variation in what's being productive.”

A few years before Pebble East was discovered, Schindler began charting those variations by using nitrogen-14 and nitrogen-15 isotopes in lake sediment. Oceans contain more of the heavy isotope than fresh water contains, so salmon have a higher percentage in their bodies than freshwater fauna. By plotting the rising and falling nitrogen-15/-14 ratio in cores of lakebed mud (where salmon sink when they expire, exhausted, after spawning), Schindler can trace demographic booms and busts back 10,000 years in some areas. He found that the population in each inland waterway—whether a mountain creek just centimeters deep, a meter-deep river from an underground spring, a lake beach, etc.—fluctuates erratically and independently of its neighbors. That's because its temperature, depth, and other qualities respond to different environmental factors—heavy rains, ice, tree cover, floods—in unique ways. Salmon also spawn or migrate back to sea as juveniles in different months, and El Niño and decades-long weather patterns fiddle with ocean habitats. Salmon thrive where conditions are favorable each decade, and given the diversity of Bristol Bay, odds are they will be favorable somewhere.

Schindler and Hilborn refer to this buffer of redundant habitats as “biocomplexity.” “Regular biodiversity focused on the biotic component of the system, like genetic diversity, population diversity, species diversity,” Schindler explains. “But that's not thinking about the coupled physical landscape. In the case of salmon, it's important to consider them together because the habitat is evolving.” Other fish scientists argue that biocomplexity underlies the health of many fish populations worldwide. George Rose of Memorial University of Newfoundland in St. John's, Canada, finds only subtle genetic differences between some of the thriving and crashing stocks of Atlantic cod he studies. “There's nothing obviously different between these fish—except they have a different home.” The reasons are murky, he says, “but one group does really well for a while, then the other does well for a while” (see sidebar, p. 264).

But that murkiness has been clearing up lately, and Schindler and Hilborn argue that the failure of some fisheries shows the folly of focusing only on productive watersheds. Dams in the U.S. Pacific Northwest—often built decades ago on nonproductive runs—have cut off spawning grounds that might have helped salmon recover when the population in other places flat-lined. In British Columbia, Canada, fishers long neglected all but the teeming Fraser River stock, which replenished itself each year. But extenuating circumstances caused the stock to collapse last summer to just 1.7 million salmon, well under the expected 11 million to 13 million, and left the industry gasping.

But the Fraser situation holds other lessons, too, claim Pebble officials. Large mines had been excavating copper within 10 km of Fraser River for decades before the salmon collapse, with seemingly no toxic effects. (Most scientists, including Schindler and Hilborn, blame the collapse on climate change or a lice infestation from fish farms.) Taylor, Pebble's environmental man, also points out that Alaska's Copper River, named after nearby and well-mined deposits, supports some of the premium salmon runs in Alaska. Moreover, the Bristol Bay salmon are hardly endangered or reeling: Schindler has never seen a higher population in his demographic studies.

Given Alaska's unreliable political climate—the state has a history of mavericks and ruthless moneyed interests (the Anchorage Daily News has a Web page to help sort through the endless federal inquiries into corruption there, http://www.adn.com/fbi)—most people declined to handicap whether Pebble Mine will actually open, much less when. Governor Sean Parnell has taken no public stand on Pebble. Neither has former Governor Sarah Palin, though her husband, Todd, works part-time fishing salmon. Nevertheless, those who read tea leaves interpret her comments and actions as pro-Pebble. Other former governors, as well as former U.S. Senator Ted Stevens, widely viewed as in favor of mining anything, have denounced Pebble.

Alaskan citizens send conflicting signals, too. Polls have shown that over half of Alaskans oppose the Pebble project, including about 70% of the people, largely Native Americans, near Bristol Bay. Then again, native groups recently opposed a strict clean-water initiative that many viewed as a referendum on Pebble, because it would have made mining there effectively impossible. (Some residents worried that the initiative would hamper all large mines in the state.) The initiative lost 57% to 43% during a statewide election in August 2008. So for now, Pebble lives, and, ultimately, Taylor feels, public pressure won't sway or disturb the regulatory agencies that will decide its fate. Pebble likely will not begin submitting permits until 2011.

Perhaps the one thing more uncertain than Alaskan politics is the potential effect of global warming on salmon runs. Alaska has grown rainier and warmer in the past few decades, and as glaciers melt and established ocean currents wobble, scientists do not pretend they can predict what will happen to spawning grounds. But really, that's the point of the biocomplexity work: Nobody can know. An empty river today could be boiling over with salmon in 20 years—if it remains habitable. “Life choices that work in one decade may not work in another,” says Hilborn. “You want something out there that's going to be doing well in a warmer world.”

12. Fisheries

# The Secret Lives of Ocean Fish

1. Sam Kean

Many scientists argue that ocean fish such as cod segregate themselves into distinct environments, as salmon do—and thrive or struggle for the same reasons.

It's easy to monitor the health of stocks of salmon because salmon spawn in small, discrete, and accessible freshwater bodies. Tracking fish in the ocean is a little tougher. But many scientists argue that ocean fish such as cod segregate themselves into distinct environments, as salmon do—and thrive or struggle for the same reasons.

For cod, population health depends on both human fishing and ecological factors. The 6 billion or so kilograms of cod living off Newfoundland and Labrador in Canada in the 1940s has dropped to hundreds of thousands of kilograms today, partly due to overfishing, says George Rose, a professor of fisheries conservation at Memorial University of Newfoundland in St. John's. “People thought little stocks [of cod] weren't important, and they got wiped out,” he says. When large stocks faltered too, nothing could replace them.

But Rose's research reveals tremendous variation in the way cod stocks responded to the collapse. “Groups … very close geographically in fact are subject to very different ecological conditions,” he says. As a result, “even in the worst possible times, in the 1990s, we had a couple of groups that were actually doing beautifully.”

Work in biocomplexity—the physical diversity of fish habitats—explains why. To terrestrial animals (such as humans), oceans look homogenous—cold, deep, and empty—says Larry Crowder, a marine biologist at Duke University in Durham, North Carolina. However, oceans have currents, canyons, mountains, reefs, and forests of plants, which alter a habitat from top to bottom. Submerged vegetation supports prey at the expense of predators, given that prey can slip away in tangles of weeds. Fish rely on submarine currents to transport eggs and larvae from nests to feeding grounds. Climate change or fishing can alter habitats, and depending on how a stock's habitat responds, its population contracts or expands.

To thrive overall, species need to hedge themselves, by finding a balanced array of habitats to supply more or fewer fish as need be. “I guess it's like an orchestra,” Rose says. “You have the horns playing for a bit, then the strings come in.”

13. Infectious Diseases

# Questions Abound in Q-Fever Explosion in the Netherlands

1. Martin Enserink

A burgeoning goat-farm sector appears to be behind the worst outbreak ever recorded in humans of a rare zoonosis that until now has been seen primarily as a rare occupational disease for farmers, veterinarians, and slaughterhouse workers and as a potential—if not very deadly—bioterror agent.

VINKEL, NETHERLANDS—Jan van Lokven has been a goat farmer for 23 years, but he's about to lose half his livelihood. Later this month, government officials will show up at his barn to kill all of his pregnant goats—more than 60% of his flock of almost 650 animals. Drinking coffee at his kitchen table, Van Lokven says he isn't sure what he'll do that day. His animals would be more at ease if he's around while the culling team does its grisly job, he says. “I just don't know if I can watch it.”

Just before Christmas, the Dutch government decided to cull about 40,000 pregnant goats at more than 60 farms in hopes of halting the worst outbreak ever of a little-known bacterial disease called Q fever. The problem isn't that the goats are suffering; it's that they are microbiological time bombs that threaten human health.

Q fever causes little disease in animals, and most farmers don't see it as a problem. But it can lead to abortions and stillbirths—and when it does, the animals' placentas and birth fluids contain many billions of microbes that spread easily into the environment. Such outbursts are assumed to have caused increasingly bigger waves of human Q-fever victims—most of whom come down with pneumonia—in the Netherlands the past 3 years. In 2009, there were more than 2300 human cases, including six deaths.

Until now, Q fever has been seen primarily as a rare occupational disease for farmers, veterinarians, and slaughterhouse workers and as a potential—if not very deadly—bioterror agent. Nobody is sure what triggered the explosive outbreak in the Netherlands, which has sickened mainly people who never had contact with animals, so the small cadre of Q-fever experts elsewhere in the world are following the Dutch struggle with fascination. “Nothing like this has ever been reported,” says Jennifer McQuiston of the U.S. Centers for Disease Control and Prevention in Atlanta. She adds that between 100 and 170 human cases are reported annually in the United States. Faced with major gaps in scientific understanding and criticism that public health has taken a back seat to farmers' interests, the Dutch government has launched a flurry of studies of the disease and of Coxiella burnetii, the intracellular bacterium that causes it.

Q fever was first described in abattoir workers in Brisbane, Australia, in 1935. Its name—short for “query” because of its mysterious nature—was meant to be temporary, but it stuck even after C. burnetii was isolated in 1937. As it turned out, the microbe can be found almost anywhere in the world, and it has a bewildering range of hosts and ways to spread. It can infect mammals, birds, and arthropods, including ticks, which contribute to its spread by producing large amounts of it in their feces.

Scientists don't understand exactly why C. burnetii amasses in the wombs of pregnant animals, but past epidemiological studies have shown that the resulting abortions—especially in sheep and goats—are by far the biggest risk factor for human infections. However, human transmission from consuming contaminated milk and cheese, getting bitten by ticks, and having sex with an infected person have been reported as well.

In the United States, Q fever is classified as a “Category B” bioterrorism agent because it would be relatively easy to use and because, although not as deadly as anthrax or plague, attacks could still create widespread disease and panic. The U.S. Army exposed human volunteers to it as part of its biowarfare program in the 1950s; the Soviet Union experimented with it as well, as did the Japanese cult Aum Shinrikyo, known for its 1995 sarin attack. Bioterror worries brought more attention to it in the '90s and prompted the United States to make it reportable in 1999.

This increased awareness—along with better diagnostic tests—may explain the rising number of reported outbreaks of Q fever over the past 10 years worldwide, says epidemiologist Didier Raoult of the Université de la Méditeranée in Marseille, France, the foremost expert in human Q fever. “Once you start looking for Q fever, you'll find more and more of it,” he says.

But what's going on in the Netherlands now is not just better detection but something new and different, says epidemiologist Roel Coutinho, head of the Centre for Infectious Disease Control in Bilthoven. When 182 human cases were detected in and around a town called Herpen in the summer of 2007, it seemed like a one-off outbreak. But in 2008, a new wave erupted, quickly filling up intensive-care units in the province of Noord-Brabant. A thousand cases were reported that year. In 2009, the number of new cases jumped to almost 2200, and the disease was found across the country.

It's still unclear what's behind the massive spread. Part of the reason has to be the recent expansion of high-intensity goat farming in the densely populated country, says Coutinho. The number of goats has quadrupled in Holland to more then 350,000 since 1995, and the number of them per farm has tripled; the country is now home to some of the biggest goat farms in the world. (In a sad twist of fate, some farmers switched to goats after a devastating swine flu outbreak ruined the Dutch pig industry in the 1990s.) Farms are often close together, and animals are frequently transported between them, presumably facilitating spread, says Coutinho. Bacteria released during abortions end up in manure, which is often spread onto farm fields; the wind may have carried them to the many surrounding towns and cities.

But Hendrik-Jan Roest, a scientist at the Central Veterinary Institute of Wageningen UR in Lelystad, says the sudden increase could be linked to a more virulent subtype of the microbe that started spreading in about 2005. Genetic typing by Corné Klaassen at Canisius Wilhelmina Hospital in Nijmegen has shown that all Dutch farms and patients are infected by a single subtype of C. burnetii. That suggests that the strain is somehow better at propagating itself than others, Roest says. He plans to compare strains in a collaborative study with Annie Rodolakis of the French National Institute for Agricultural Research in Tours, who has developed a mouse model of Q fever.

A more urgent question is how to bring the outbreak under control. In 2008, veterinary and public health authorities hoped that hygienic measures, such as a ban on distributing manure on farm fields, would help reduce human exposure. Now, the hope is that an animal vaccine produced by CEVA, a French company, can help bring the microbe under control. In short supply in 2008 and '09, the vaccine will be plentiful this year, says Christianne Bruschke, chief veterinary officer at the agriculture ministry. The vaccine does not prevent all infections, but it does prevent most abortions, which should help curtail the spread of the disease.

The vaccine does not work in infected animals, however, which is why an expert panel recommended in early December the emergency slaughter of all pregnant goats at affected farms. (There is no reliable way to quickly distinguish infected goats from healthy goats.) Bruschke says the cull is a one-time measure to prevent another massive release of microbes in the spring of 2010, when the goats would normally give birth. Then from 2011 on, the effects of the vaccine should start kicking in.

The impact on some farmers could be devastating, says Van Lokven. The Dutch government reimburses farmers for the current value of the goats but doesn't do so for the loss of income while they rebuild their flocks.

How well the measure will work is unclear as well. The huge numbers of C. burnetii already in the environment may persist for months or years; there's no good way to measure their numbers or to assess the threat they pose, says Roest. And there are many other questions. Although there is little doubt that goat farms are key amplifiers in the current outbreak, the role of cattle farms is unclear. For now, most experts say another surge of human cases this spring is inevitable—they just hope it will be smaller than that of 2009.

14. Infectious Diseases

# Humans, Animals—It's One Health. Or Is It?

1. Martin Enserink

A "holistic approach" and "synergism" working for the health of all species are the buzzwords of the One Health movement, which aims to bring veterinary and human health closer together. But the Dutch Q-fever outbreak provides a vivid example of how those two worlds often don't get along, especially when the stakes are different for each.

A “holistic approach” and “synergism” working for the health of all species. Those are the buzzwords of the One Health movement, which aims to bring veterinary and human health closer together. Because people and animals form such a close-knit ecosystem—and most new or re-emerging diseases come from animals—the classic divide between veterinarians and doctors is hampering disease control, three scientists argued when they began promoting the concept 3 years ago (Science, 15 June 2007, p. 1553).

But the Dutch Q-fever outbreak provides a vivid example of how those two worlds often don't get along, especially when the stakes are different for each. Public health officials have complained that the veterinary community didn't properly inform them and that the outbreak spiraled out of control in part because economic interests trumped human health. “Sure, One Health, it's a nice concept, but we clearly have a long way to go,” says Roel Coutinho, head of the Centre for Infectious Disease Control.

What makes Q fever tricky is that the vast majority of animals are healthy and asymptomatic, says French epidemiologist Didier Raoult of the Université de la Méditeranée in Marseille, France. The disease does trigger some abortion and premature birth, but the economic damage is limited, so there's little incentive to do anything about an outbreak. “The vets don't care about it,” says Raoult—and human health suffers as a result.

Animal health authorities were slow to investigate suspected farms even as human cases started pouring into hospitals in 2008, says Jos van de Sande, a doctor at a regional health service in Noord-Brabant, the hardest-hit province. To protect farmers from stigmatization, Van de Sande and his colleagues weren't told the exact location of contaminated holdings, only the general area. “You can't fight an epidemic like that,” he says. Coutinho adds: “We just weren't able to get across how serious the human problem was getting.”

Christianne Bruschke, the country's chief veterinary officer, dismisses those claims. From the onset, policy was set by a working group with members from both the agriculture and the health ministries—and it included Coutinho and other scientists. “They should have spoken up before if they disagreed,” says Bruschke. She says the government had to strike a balance between farmers' interests and public health in the face of insufficient data about how Q fever spread: “You can't impose draconian measures on farmers if you have no idea whether they will have an effect.”

The Dutch government plans to investigate how the epidemic was handled. Coutinho says one lesson is already clear: Veterinarians should notify their colleagues in public health anytime a zoonotic disease starts spreading in animals—as Q fever did in 2005, 2 years before the human explosion began.