I Engineer seeks funding

£ After a year of making ammunition and

8 explosives for a Canadian firm, Kavli got his U.S. visa. His first job, in southern California, was designing flight-control transducers for the Atlas missile. "I had only been out of college 1 year, and they made me chief engineer," he marvels. "I discovered very soon that in America you didn't need to know anything. You just needed to ask the right questions."

Kavli soon itched to step out on his own. He did so in 1958 with a two-line ad in the

The Kavli Family

Kavli Institute for Theoretical Physics (December 2001)

University of California, Santa Barbara

Astrophysics, condensed matter physics, string theory, biophysics

Kavli Institute for Particle Astrophysics and Cosmology (January 2003)

Stanford University/Stanford Linear Accelerator Center Astrophysics, high-energy physics, cosmology

Kavli Institute for Brain Science (March 2004)

Columbia University Neural circuitry and plasticity, mediation of complex behaviors

Kavli Institute for Brain and Mind (March 2004)

University of California, San Diego

Origins, evolution, and mechanisms of human cognition

Los Angeles Times: "Engineer seeking financial backing to start own business." "Surprisingly enough, I got several responses," he says with a laugh. The company, soon called Kavlico, was born.

Throughout the 1960s and 1970s, Kavlico grew into a major supplier of pressure, position, and force sensors for commercial airplanes and military jets, bombers, and missiles. In 1976, Kavlico outcompeted 41 companies to land a contract with Ford Motor Co. for automotive sensors. Kavli found that the transition to producing cheap but reliable sensors for cars was excruciatingly difficult. "I wouldn't have done it if I had known. Ignorance is bliss," he says. But ultimately, the automotive contracts made Kavlico's value soar. A Canadian conglomerate bought the company from Kavli in 2000 for $340 million.

"I had no doubt I would succeed," says Kavli, "but I could not have been as successful anywhere else."

Building the foundation

For years, Kavli repaid his gratitude by donating to civic causes in Ventura County and Santa Barbara County, such as the Fred Kavli Theatre for the Performing Arts in Thousand Oaks. But his company's sale enabled him to set up his Kavli Foundation and leave his mark upon science. His themes of astrophysics, nanoscience, and neuroscience—"from the largest, to the

Kavli Institute for Cosmological Physics (March 2004)

University of Chicago Dark matter and energy, cosmology, neutrinos, and cosmic rays

Kavli Institute for Neuroscience (March 2004)

Yale University Development, cellular organization, and function of the cerebral cortex

Kavli Institute for Astrophysics and Space Research (August 2004)

Massachusetts Institute of Technology

Space science, gravitational physics, dark matter and energy smallest, to the most complex," in Kavli's words—reflect both his industrial expertise with micromachinery and his deeply held fascination about the extremes of nature (see table, above).

To run the foundation's programs, Kavli recruited physicist David Auston from the presidency of Case Western Reserve University in Cleveland, Ohio. A member ofboth the National Academy of Sciences and the National Academy of Engineering, Auston shares and enacts Kavli's philosophy.

"I have a real concern about the argument that many scientists and universities promulgate these days, that science is good for the economy," Auston says. "If that is your only short-term goal, you'll be disappointed in most cases. Our foundation is really distinct in that regard. We are dedicated to long-term—and in some cases high-risk—basic research that advances knowledge as its goal."

Kavli Institute of Nanoscience (March 2004)

Delft University of Technology, Netherlands Protein nanomachinery, molecular electronics, quantum information

Kavli Nanoscience Institute (March 2004)

California Institute of Technology Nanobiotechnology, nanophotonics, integration of nanosystems

Kavli Institute for Nanoscale Science (March 2004)

Cornell University Signal communication of cells, collective behaviors of nanostructures

A Physics Home Away From Home

The peach, orange, and mango tones are clues that Kohn Hall isn't your typical academic building. Then there are the light maple furniture and green carpeting, the wall-size Vermont slate blackboards, and the giant round windows in a hexagonal tower that glows like a lighthouse at night. In the New Age words of a promotional article, it is "a warm, inviting environment that simultaneously relaxes and alerts the visitor's mind." However, funding constraints are casting a chill inside the hall's cozy womb.

The building houses the Kavli Institute for Theoretical Physics (KITP), formerly known as ITP. Established in 1979 after a national competition, ITP was created for the community to use. "This was the first institute in physics based on visitors," says University of California, Santa Barbara, physicist Robert Sugar, part of the proposal team. "It was very controversial at the time."

But in its 25 years, the institute has grown to play a central role in the intellectual lives of most theoretical physicists. Scientists come by the dozens for "programs" on emerging topics that last from a few weeks to several months. They leave classes and committees behind to think and talk within the building's residential atmosphere. Recent programs ranged from the physics, chemistry, and mineralogy of Earth's interior to the intersection between string theory and strong nuclear interactions.

Warm retreat. Nobelist David Gross oversees a national physics institute housed in striking Kohn Hall.

"When people are here, they're in a different state," says astrophysicist Lars Bildsten, one of KITP's five permanent members. "You really see them get refreshed." Or in the words of astrophysicist Kip Thorne of the California Institute of Technology in Pasadena: "Thank god for the KITP."

With 1000 visitors each year, it's common to see cosmologists, string theorists, biophysicists, condensed matter physicists, particle theorists, and others forge new ties, Bildsten says. "Everyone higher up in the [academic] food chain talks about the importance of interdisciplinary research, and we say, 'Indeed.We have a model for that.'"

Fred Kavli entered the picture in 2001, when the Kavli Foundation awarded a $7.5 million grant to ITP. Now, Kohn Hall features more offices and dramatic new spaces thanks to a $6 million expansion funded out of the grant. Designed by the building's original architect, Princeton-based Michael Graves, the hexagonal tower is proving a popular meeting place.A newly enclosed outdoor courtyard—with the Vermont slate—has led to open-air chats. "Theoretical physicists are incredibly collaborative and interactive," says KITP director David Gross. "They don't need labs; they just need a blackboard."

The staff also webcasts and archives talks from a striking new auditorium, which seats 50 within tightly curved rows so that everyone can see everyone else. Fifteen ceiling microphones pick up every word, so some physicists have stifled their nasty asides, Bildsten jokes.

But Kohn Hall's new spaciousness also frustrates Gross, for he lacks the budget to take full advantage of it. Flat funding from the National Science Foundation has eroded KITP's abilities to support visitors and run pro-grams."We built this for the community," says Gross,"but now we are funds limited. I regard it as an outrageous, scandalous tragedy."

With just Auston and Kavli at the helm and a couple of support staffers, the foundation does not respond to unsolicited proposals. Rather, the two conduct dozens of site visits in search of what Kavli calls "winning science teams with the very best supporting organizations." From the leading candidates, they ask for simple proposals that strip basic mysteries to their essence: the links between cosmology and string theory, the nanomachinery of proteins in cells, the evolution of thought.

"If you applied for [federal] grants asking these questions, you would be laughed off," says neuroscientist Pasko Rakic ofYale University, director of the Kavli Institute for Neuroscience. "They want to know which subunit of which channel you want to study for the next 3 years. But [Kavli] wants to ask the big questions."

Auston and Kavli ask the host universities to support the institutes with more funds, infrastructure, faculty recruitments, and the like. Moreover, they expect researchers within each of the three themes to collaborate. In the near future, a grand assembly may involve all 10 institutes— soon to be 12, with the expected addition of others in Europe and Asia.

By all accounts, there is no pressure to do science in a "Kavli way." "Our initial reaction [to the new institutes] was a loss of uniqueness," says UCSB physicist Joseph Polchinski. "We all wondered, 'Are we now part of a chain?' But no, each of these Kavlis retains its unique identity." Indeed, Kavli seeks independent and strong-willed scientists who won't hesitate to plunge in unforeseen directions. In return, he asks only for periodic reports and occasional invitations to special programs.

The researchers are not as sanguine about the foundation's plan to bestow three $1 million Kavli Prizes, one within each theme, biennially starting in 2007. Auston and Kavli feel that a grand ceremony, possibly conducted in Oslo, eventually could rival the Nobel Prizes in public impact. But several at UCSB worry that the effort will land with a thud in the prize-heavy fields.

To the recipients of Kavli's largess, it's a minor point. "As a donor, he's a jewel," says physicist David Gross, KITP's director and one of the latest set of Nobel laureates. "He doesn't interfere. You hear a lot of horror stories with other donors. They give money and then lots and lots and lots of advice."

Ever the businessman, Kavli trusts his investments. His only advice is to keep working at the frontier toward a future he will not see and cannot imagine. "Fred wants this foundation to exist in perpetuity," says Auston. "He will dedicate his entire wealth to that goal."

-Robert Irion


Twisted Parasites From "Outer Space" Perplex Biologists

A bizarre group of parasitic insects challenges the biological rule book

The odd group of insects called twisted-wing parasites, or more formally Strepsiptera, is easily overlooked. Spending most of their lives hidden inside other insects, the majority of the 596 known species have been identified only from adult males caught during their brief mate-seeking flight. "These are really, truly enigmatic insects," says David Grimaldi, entomology curator at the American Museum of Natural History in New York City. "They break all the rules."

The differences between males and females of the same strepsipteran species are extreme. Adult males are small, flylike creatures, whereas most adult females resemble grubs and remain inside their host, merely protruding their fused heads and thoraces when ready to receive a male's sperm. In one strepsipteran family, males and females actually parasitize different kinds of insects. "Everything you find about them is like they came from outer space," says population geneticist J. Spencer Johnston of Texas A&M University in College Station.

Unlocking the secrets of how these strange parasites originated and how they maintain their bizarre lifestyle promises to deliver new insights in evolutionary and developmental biology, says Jeyaraney Kathirithamby, an insect evolutionary taxonomist at Oxford University in the United Kingdom. She and Johnston have recently turned up oddities in the strepsipteran genome and begun to tease out how the parasites survive within their hosts. Kathirithamby and researchers in Papua New Guinea have even enlisted Strepsiptera in the battle against important insect pests.

Quirky physical characteristics and lifestyle have made Strepsiptera tough to place in the insect family tree, notes Grimaldi. Some systematists group them with the beetles, others with flies. Grimaldi, however, has recently analyzed a primitive strepsipteran found in Cretaceous amber and says it doesn't resemble either flies or beetles. Meanwhile, he adds, molecular analyses of strepsipteran phylogeny have been "at best controversial."

The sequencing of a strepsipteran genome could resolve its phylogeny, but no organization has stepped forward so far to fund such an effort. Last month, however, a team led by Kathirithamby and Johnston reported online in Insect Molecular Biology that the strepsipteran Caenocholax fenyesi has the smallest documented genome of any insect. In still-unpublished work with graduate student Joseph Gillespie of Texas A&M, they also discovered that the ribosomal DNA of this species has a unique structure. "They're just so different from everything else," says Johnston.

Strepsipterans parasitize 34 families across 7 of the 32 orders of insects, most commonly wasps, bees, and Hemiptera (true bugs). The discovery last year that the larvae of one species, Stichotrema dallatorreanum, wrap themselves in a bag created from their katydid host's epidermis, thereby eluding an immune response, may explain how strep-sipterans are able to parasitize such a wide range of hosts. But Kathirithamby and Johnston think it's possible that this strategy only evolved in the family Myrmecolacidae to whichS. dallatorreanum belongs.

For most parasites, males and females prey upon the same host. Myrmecolacids

Strange pair. Strepsipteran males (left) and females (right) look very different and, in one family, parasitize completely different hosts.

are an exception: They are the only group of parasitic insects in which male and female larvae enter completely different hosts, notes Kathirithamby. The males parasitize ants, whereas females take up residence in crickets or grasshoppers. An intriguing question, says

Kathirithamby, is whether myrmecolacid larvae start life sexless and only become male or female once they enter an ant or cricket. "To date, there is no organism that determines its sex by its host, but it makes sense to me," says Johnston. It's possible that a signal from the host sets off a cascade of sex-determining genes, he adds.

Studying sex determination in myrmeco-lacids is no easy task. The differences between the sexes have made it difficult to find the females and match them to males of the same species. Kathirithamby and Johnston scored a first last year when they used DNA analyses to match male and female specimens of C. fenyesi from Mexico.

At the same time, they discovered that there are significant differences between the DNA sequences of two genes in C. fenyesi males from Texas (which parasitize red imported fire ants) and identical-looking males from Mexico (which parasitize other ants). That suggests that these insects are actually separate species, or are on the verge of becoming so, because they have different hosts. "What is puzzling us is how this speci-ation is going on," says Kathirithamby.

Understanding the basic biology of strepsipterans may prove useful in controlling insect pests, such as those ravaging coffee, rice, and oil palm crops. S. dallatorreanum is already a hit with oil palm growers in the Papua New Guinean island of West New Britain; since its introduction in 2000, it seems to have reduced katydid numbers and lessened oil palm damage.

Whether strepsipterans could also control U.S. red imported fire ants remains an open question. Jerry Cook, an entomologist at Sam Houston State University in Huntsville, Texas, has estimated that C. fenyesi is unlikely to be effective because it parasitizes only 1% to 2% of ants. Kathirithamby and Johnston think that this is an underestimate; in large fire ants, parasitism rates run as high as 55%, they say.

Still, Johnston acknowledges that the "funny biology" of strepsipterans may create a hitch. Fire ants naturally eat any insect in sight, including crickets, the most probable hosts of C. fenyesi females.

-Fiona Proffitt

Indian Ocean Tsunami

Using Scientific Assessments to Stave Off Epidemics

In devastated villages and refugee camps, aid workers are racing to stay ahead of and systematically block microbes that could prove as deadly as the tsunami

At least one early-warning system in Indonesia is in place and working. On the morning of 8 January, World Health Organization (WHO) officials in Banda Aceh received a call from a relief worker reporting a case of measles—one of the biggest potential killers of children during humanitarian disasters. The team confirmed it within hours; by afternoon, health officials and aid workers were able to vaccinate more than 1000 people in the sick child's village.

The danger is far from over: WHO estimates that only a quarter of the children in the Aceh area have received a measles vaccination. But the quick and effective response to this case—and another a few days later—is one example of the kind of science-based approaches that relief organizations are bringing to the region devastated by the tsunami, says Ronald Waldman of Columbia University, who helped coordinate WHO's team in Banda Aceh.

As soon as the extent of the tsunami's devastation became clear, WHO and relief agencies went into overdrive to try to prevent what all too often occurs in the aftermath of natural or humanmade disasters: killer outbreaks of communicable diseases that can sometimes claim more lives than the original disaster itself. Ten years ago such efforts were well meaning but often ineffective and were considered secondary to providing food and housing. But a better understanding of the epidemiology of so-called complex emergencies has changed relief agencies' priorities. "The question is determining what can cause a large amount of death quickly and then ensuring that we prioritize our efforts accordingly," says Peter Salama, an epidemiologist and relief expert who works with UNICEF and USAID.

Paul Spiegel, a physician and relief expert with the United Nations High Commissioner for Refugees, credits Waldman with helping pioneer the use of epidemiology and other sci-

8 ence-based assessments in disaster relief

i efforts. Waldman and Michael Toole, now of the Burnet Institute in Melbourne, Australia, | published a 1990 study showing that vaccine-3 preventable measles infections had helped push the mortality rate of children in Ethiopian and Sudanese refugee camps to 60 times the normal rate. Even though measles is well known as a major child killer, the finding surprised many public health and aid agency workers, Spiegel says: "Before that, people just weren't looking that closely."

Now they are looking. Indeed, WHO identified disease surveillance, along with water and sanitation, as one of the top priorities for the tsunami-affected region. "The key issue here is to make sure we hear about the first 10 or 20 suspected cases" instead of the 200th, says Maire Connolly, who heads the Communicable Diseases in Complex Emergencies program at WHO. Aid workers need to be able to recognize the signs of the major killers and confirm a diagnosis as soon as possible, she says. One of the most notorious examples of a relief effort that failed is the 1994 epidemic of cholera and dysentery in a camp sheltering Rwandan refugees in Goma, Democratic Republic of Congo. The outbreak killed an estimated 50,000 people in 3 weeks. "Ifwe had had [these techniques] in 1994," Connolly says, "it is possible we could have prevented that major outbreak."

The measles report in Aceh came the first morning after Waldman and his colleagues met with nearly two dozen relief organizations to hand out and explain the agency's standardized form—tailored to local condi tions—for recording and reporting epidemic-prone diseases.

The forms ask workers to notify authorities of signs of potential killers in 10 categories: measles, cholera, dysentery, meningitis, malaria, acute respiratory infections, jaundice, hemorrhagic fevers, any fever of unknown origin, and any acute clusters of disease that can't be explained. Such surveillance will also pick up tetanus, Japanese encephalitis, and hepatitis A and E—as well as unknown killers that could emerge, Connolly says.

Many of the affected areas already had disease surveillance teams in place, says Aberra Bekele, medical director for UNICEF in Sri Lanka. In India, workers trained to immediately report any signs of polio are being tapped to watch for diseases such as cholera, typhoid, and malaria. In Sri Lanka too, Bekele says, efforts are focused on supporting the existing disease monitoring system and expanding it to include possible disaster-related epidemics. Ideally, he says, the efforts will leave behind a stronger system for the long term.

A crucial part of that system will be diagnostic labs that can quickly tell the difference between diarrhea caused by relatively benign viruses and that caused by deadly cholera, Connolly says, as well as perform immunological tests for hepatitis, Japanese encephalitis, and leptospirosis—a major concern following floods.

"We are better prepared than we would have been 5 years ago," Connolly says. "We now have refined tools for the early-warning systems. We have access to standard protocols for dealing with cholera. We have recommendations for what should be in a stockpile, what field workers should have in an investigation kit."

But to use those tools, relief workers must reach the people in need. In spite of intense efforts, the tsunami's destruction prevented aid workers from reaching the northwest coast of Aceh for nearly 3 weeks, leaving officials worried that preventable disease—especially malaria and leptospirosis—may be spreading. "I won't be satisfied until 100% of the population is reached," Waldman says. "There was a blind spot" along the coast, agrees David Nabarro, head of WHO Crisis Operations. But he is cautiously optimistic. "You can have an epidemic of an infectious disease anytime . until you have improved sanitation and a safe water supply," he says. But with the surveillance system now in place, "it would be very hard for a major outbreak to take root and cause mass mortality." -Gretchen Vogel

With reporting by Martin Enserink.

Preventive medicine. Health workers hope that mass vaccination campaigns will block any spread of measles in the Aceh region.

Meeting Society for Integrative and Comparative Biology

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