# News this Week

Science  25 Nov 2011:
Vol. 334, Issue 6059, pp. 1038
1. # Around the World

1 - Beijing
Chinese Climate Report Paints Grim Picture
2 - Geelong, Australia
Imaging Infection in Real Time
3 - Brussels
E.U. Bans 'Backscatter' Body Scanners
4 - Shenzhen, China
Sequence Everything: BGI Thinks Big

## Beijing

### Chinese Climate Report Paints Grim Picture

Rising sea levels could submerge 18,000 square kilometers of China's vulnerable low-lands by 2080, according to a Chinese government report released on 15 November. Taking stock of environmental changes sweeping China, the Second National Assessment Report on Climate Change notes that China's glaciers receded 10% over the past 60 years, while average land surface temperatures increased by 1.38°C from 1951 to 2009.

Future prospects are even grimmer, the report warns. Sea levels off the coast of Shanghai are predicted to rise up to 148 millimeters by 2030, while the Pearl River, which cuts through a densely populated swath of southern China, is expected to swell to 210 millimeters by 2050.

Such findings may help China appeal to the international community for help, Li Hui, deputy director for science and climate change at the China Meteorological Administration, insinuated in comments reported by China Meteorological News Press. The report, Li said, “provides important support for China's participation in international climate negotiations.”

## Geelong, Australia

### Imaging Infection in Real Time

In the Hollywood blockbuster Contagion, a breakthrough against a lethal bat-borne virus comes from unheralded Geelong, Australia. That's not at all far-fetched: The city in Victoria state hosts the Australian Animal Health Laboratory, which its director, Martyn Jeggo, calls the most advanced biosecure facility in the world. Now, the hot zone-style lab is even better equipped for pioneering work.

Last week, the lab unveiled an AUS $11.5 million (U.S.$11.6 million) facility to image the world's worst viruses infecting cells in real time. Until now, high-security labs could only do microscopy on dead viruses. “It's like going from still pictures to movies,” says bat virology program leader Linfa Wang, whose team helped identify the Nipah and Hendra viruses.

The new facility is equipped with a video link so researchers worldwide can participate in a virtual lab. “We need these interactive interdisciplinary teams,” Wang says. “Speeding up the identification of a virus by days will save lives in an outbreak.”

## Brussels

### E.U. Bans 'Backscatter' Body Scanners

The European Union this week adopted new rules for airport security scanners, including a ban on the x-ray body scanners deployed in major U.S. airports. “Only security scanners which do not use X-ray technology are added to the list of authorised methods for passenger screening at EU airports,” reads the statement, released 14 November.

The U.S. Transportation Security Agency (TSA) began rolling out its scanners in 2007. TSA says on its Web site that the technology is “safe and meets national health and safety standards.” But in April 2010, four scientists at the University of California, San Francisco, sent a letter to the White House Office of Science and Technology Policy, arguing that the scanners focus the dose of ionizing radiation on the skin and that additional safety review was needed. The European Union seemed to agree, noting that, for now, it was banning the technology “in order not to risk jeopardizing citizens' health and safety.” A special E.U. committee will review potential health effects from the scanners and report back in April 2012.

## Shenzhen, China

### Sequence Everything: BGI Thinks Big

“We have a dream to sequence every living thing on earth, to sequence everyone on earth,” Yang Huanming, a founding partner of BGI, the Chinese DNA sequencing powerhouse, said at a conference here last week. They're giving it their all. At the 6th International Conference on Genomics, participants discussed a raft of programs that will sequence thousands of crops, animals, and insects—and, in humans, unravel the genomics of Mendelian diseases and pave the way for personalized medicine. New BGI collaborations include work with Johns Hopkins University in Baltimore to develop synthetic yeast, with the International Rice Research Institute of Los Baños, Philippines, to capture the genomic diversity of 3000 rice strains, and with a group from Karolinska Institute, in Stockholm to study its collection of tissue from patients with primary immunodeficiency disorders. BGI provides sequencing muscle and bioinformatics support; its partners bring samples and expertise from their disciplines. “Collaboration is our theme,” says Yang.

2. # Newsmakers

## Italy Names New Research Minister: Francesco Profumo

Italy's new government has chosen Francesco Profumo, the relatively green chief of the national research agency, to be Minister for Education, Universities, and Research. Prime Minister Mario Monti made the announcement 16 November.

Just 3 months ago, Profumo, 58, was named president of the National Research Council (CNR), the nation's main science agency, which boasts a basic research budget of €1 billion. Profumo is also provost of the Polytechnic University of Turin. He must resign the university post and is expected to step down from the CNR presidency as well.

The task ahead won't be easy. Italy devotes a relatively low fraction of gross domestic product to R&D (about 1.1%), and public support of science is unsteady. The main funding instrument, the Italian Research Project of National Interest (PRIN), is plagued with hiccups: PRIN 2009 was announced only a few months ago, promising €106 million. Researchers are still waiting for the PRIN 2010 and PRIN 2011 announcements. Meanwhile, the government has been steadily trimming university budgets. http://scim.ag/FranProfumo

## National University of Singapore Clears Ito of Misconduct

The National University of Singapore (NUS) on 15 November cleared cancer researcher Yoshiaki Ito of allegations of data fabrication in a 2002 Cell paper that sparked a nasty scientific brawl. The paper claimed that a gene known as Runx3 suppresses gastric cancer; Yoram Groner of the Weizmann Institute of Science in Rehovot, Israel, asserts that Runx3 gene expression cannot be detected in the gastrointestinal tract. After publishing his latest paper to that effect online on 8 August in EMBO Molecular Medicine, Groner filed a complaint with NUS alleging that Ito's original results “could not possibly be reached in the first place” (Science, 28 October, p. 442). NUS's investigation was unequivocal: It found “no evidence for research misconduct on the part of Prof Ito.”

That doesn't settle the scientific dispute. “My only concern in this matter is removal from the research literature of the erroneous and misleading information published in the 2002 Cell paper,” Groner wrote in an e-mail to Science. In his own statement to Science, Ito declared that the 2002 findings have been replicated by his group and others. “We are convinced that this is correct,” he wrote.

3. # Random Sample

## Mongolia's ‘Ice Shield’

As the coldest capital on Earth, you might think the last thing Ulan Bator needs is more ice. But that is just what it's about to get under a geoengineering trial aimed at “storing” freezing winter temperatures to cool and water the city during the summer.

At the end of this month, engineers will drill a series of bores through the ice on the Tuul River, pump up water from below, and spray it on the surface where it will freeze. This process will be repeated throughout the winter, adding layer after layer to create a chunk of ice that will be 7 or 8 meters thick by the spring. It's an attempt to artificially create the ultra-thick slabs—known as naleds in Russian—that occur naturally in far northern climes when rivers or springs push through surface cracks. Nomads have long made their summer camps near such phenomena, which melt much later than normal ice.

Flanked by desert and plagued by summer temperatures that can rise close to 40°C, Ulan Bator's municipal government hopes the \$724,000 experiment will create a cool microclimate and provide fresh water as the naled melts.

ECOS & EMI, the Anglo-Mongolian company behind the plan, has still greater ambitions. “Everyone is panicking about melting glaciers and icecaps, but nobody has yet found a cheap, environmentally friendly alternative,” says Robin Grayson, a geologist in Ulan Bator for ECOS & EMI. “If you know how to manipulate them, naled ice shields can repair permafrost and build cool parks in cities.” The process, Grayson says, can be replicated anywhere where winter temperatures fall below −5°C for at least a couple of months.

4. # Mysteries of the Cell

1. John Travis

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We live in the golden age of genetics, but the fundamental unit of biology is still arguably the cell. The scientists gathering next week in Denver for the American Society for Cell Biology's annual meeting need little reminding of that, but as they detail their latest insights and data, it's useful to reflect on how much of the cell remains unexplained or unknown. To that end, our news staff, aided by Science Editor-in-Chief Bruce Alberts and editors Stella Hurtley and Valda Vinson, have polled some of our Board of Reviewing Editors and other biologists to identify the cell's lingering mysteries. The handful we highlight here range from basic questions, such as how does a cell know its size, to more obscure, perplexing puzzles. And if those aren't enough to inspire you, we've noted another batch of cellular mysteries that could provide fodder for future Ph.D.s—or Nobel Prizes.

5. Mysteries of the Cell

# Do Lipid Rafts Exist?

1. Mitch Leslie

Many scientists argue that the molecular platforms that sail on the cell's outer membrane, known as lipid rafts, either don't exist or have no biological relevance, but their supporters insist the idea remains afloat.

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The contention that molecular platforms known as lipid rafts sail on the cell's outer, or plasma, membrane has kept researchers debating for more than a decade. Although many scientists argue that rafts either don't exist or have no biological relevance, their supporters insist the idea remains afloat.

Cell biologist Kai Simons, now at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, and his colleague Elina Ikonen christened the term “lipid raft” in a 1997 Nature paper that detailed the concept. At the time, the main model of the plasma membrane portrayed it as a sea of lipids through which proteins drifted with little or no organization. But the duo proposed that two kinds of lipids, cholesterol and sphingolipids, huddle together in the membrane, producing stable formations they called rafts. One line of evidence for that concept, the team noted, was the goop left behind in test tube studies when certain detergents dissolve the plasma membrane. This so-called detergent-resistant membrane oozes with cholesterol, sphingolipids, and select membrane proteins.

Rafts serve the cell, the hypothesis suggested, because they gather in one place the proteins necessary for a particular task, such as importing material or relaying a message across the plasma membrane. Proposed passengers on the rafts included glycosylphosphatidylinositol (GPI)-anchored proteins, which adhere to the outer layer of the plasma membrane and perform functions such as receiving signals and helping cells stick together.

The idea roiled the cell biology community. “Right away, there were two camps,” Simons says. “One camp didn't believe a word.” But plenty of scientists hopped aboard. More than 3000 papers later, the activities attributed to lipid rafts include promoting drug resistance in cancer cells and serving as escape hatches for viruses such as the ones that cause flu. Possibly the most debated hypothesis invoked rafts to explain the activation of the T cell receptor, the cell surface protein that spurs these immune cells to action when a pathogen is on the loose in the body. Incorporating the receptor into a raft helps switch it on, studies have suggested, possibly by allowing the receptor to hobnob with other proteins necessary for stimulating the T cell or because those proteins need the raft environment to work.

Members of both camps concur that the raft concept was compelling and galvanized investigation into membrane organization. “The raft hypothesis is brilliant in some ways,” says biophysical chemist Jay Groves of the University of California, Berkeley. “My personal opinion is that the very idea of rafts enriches scientific research,” says biophysicist Sarah Keller of the University of Washington, Seattle, “whether or not rafts exist in either specific cases or more generally.”

But how solid is the proof there are rafts? Skeptics abound, and they've scored some hits on the original raft evidence. Membrane biologist Michael Edidin of Johns Hopkins University in Baltimore, Maryland, says the field has fallen victim to what he calls the “sins of detergent extraction.” Too many researchers have assumed that detergent-resistant membranes are genuine rafts, even though studies reveal that extraction can disrupt their composition. “The idea of these isolatable islands of raft lipids is probably not viable,” says membrane biologist Ken Jacobson of the University of North Carolina, Chapel Hill.

According to the raft hypothesis, certain lipids naturally sort themselves to create the organized pockets of proteins that make up rafts. But many researchers don't buy that mechanism for inducing order in the membrane. It is too passive, especially when the plasma membrane is constantly churning, says Satyajit Mayor, a membrane biologist at the National Centre for Biological Science in Bangalore, India. Instead, he says, his group's research points to a more active process in which “the cell is using energy to construct regions in the membrane.” Groves says the original hypothesis gave lipids too much credit—and proteins too little. “Proteins define their own environment. Lipids almost completely follow their behavior,” he says.

Critics have also griped because the vital statistics of lipid rafts, such as their size and life span on a cell membrane, have proven so difficult to pin down. In an early study, Simons and colleagues estimated the diameter of rafts at about 50 nanometers, or more than 3000 sphingolipid molecules across. In a 2006 attempt to sharpen the raft definition, a group of membrane researchers suggested a size range of 10 nanometers to 200 nanometers, and other estimates have come in higher or lower.

Rafts still have their supporters, however. Akihiro Kusumi, a membrane biophysicist at Kyoto University in Japan, says that if researchers specify raft criteria, such as size, and spell out which isolation techniques they use, they can demonstrate structures that qualify as rafts. For his part, Simons acknowledges the failings of detergent extraction but counters that new cell imaging techniques are adding to the evidence for rafts. Researchers using one form of super-resolution microscopy, known as stimulated emission depleted microscopy, found in 2009 that sphingolipids and GPI-anchored proteins tarried in certain molecular clusters in the membrane, as if they briefly joined rafts.

Cell biologists say it's important to resolve the lipid raft debate eventually because the plasma membrane controls what enters and exits cells and how they send and receive signals. Although researchers have proposed several alternatives for how the plasma membrane organizes itself, none of them has caught on. But if a better explanation rises to the surface, cell biologists will have to give some of the credit to rafts.

6. Mysteries of the Cell

# How Does a Cell Know Its Size?

1. Mitch Leslie

Researchers have finally begun to identify potential size-sensing mechanisms within cells, but they admit there's still a lot to learn.

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From short and heavy to tall and thin, people come in various sizes—and so do their cells. An egg cell dwarfs a sperm, for example, and both are dainty compared with some of our neurons that stretch to more than a meter in length. But within specific cell types, cells actually stick to “a fairly narrow range of sizes,” says cell biologist Marc Kirschner of Harvard Medical School in Boston.

Biologists have puzzled over how cells know when they've reached the right size. “The question has been there for a long time. The answers haven't,” Kirschner says. Researchers have finally begun to identify potential size-sensing mechanisms within cells, but they admit there's still a lot to learn.

When a cell does deviate from the norm, it may signal a malfunction: Skewed cell size is a hallmark of some diseases. Take small-cell carcinoma, a type of cancer that usually sprouts in the lungs, in which tumor cells are so puny that they barely have room for any cytoplasm.

“Cell size control doesn't just happen by itself,” notes cell biologist James Umen of the Donald Danforth Plant Science Center in St. Louis, Missouri. To understand how cells manage their dimensions, researchers have been searching for a “sizer” that enables cells to gauge how big they are. The challenge for cells is “how do you make a measuring stick?” says cell biologist James Moseley of Dartmouth Medical School in Hanover, New Hampshire.

It might not be as hard as you think. Instead of inventing specialized measurement tools, cells may take advantage of existing mechanisms and reactions that serve other purposes, says biomedical engineer David Odde of the University of Minnesota, Twin Cities. Possible measuring sticks, his work suggests, include an activated enzyme that is gradually switched off as it travels through the cell and microtubules, fibers that are continually extending and shrinking within the cytoplasm. “Any cellular reaction which has diffusion in it can sense spatial scales by the time it takes” for something to cross the cell, explains biophysicist Petra Schwille of the Technical University of Dresden in Germany.

Researchers have uncovered the best evidence for a sizer in single-celled organisms. In papers independently published in 2009, Moseley and colleagues and a second group from the University of Lausanne in Switzerland identified one way that certain kinds of yeast cells measure themselves. A so-called fission yeast cell lengthens as it grows, until it reaches a point at which it splits in the middle to form equal-sized daughter cells. The groups found that this behavior depends on Pom1, a protein whose concentration is high at the ends of the elongated cells but falls off toward the center. As the yeast cell lengthens, the amount of Pom1 at its midsection dwindles until too little remains to block a molecular circuit that curbs mitosis. Voilà! The cell begins to divide.

Research by microbiologist Petra Levin of Washington University in St. Louis and colleagues suggests that at least some bacteria have a size sensor. The size at which most bacteria divide depends on how well they are eating. If food is abundant, they reproduce at a larger mass than when meals are scarce. Levin's group identified a molecular circuit, which includes the enzyme UgtP, that senses food availability, helping the cell decide when to split. The cell's mass also influences this decision, suggesting that the cell has a system to gauge how big it is, although how the cell does this remains uncertain.

A yeast or bacterial cell is typically an individualist, relying only on itself. But in multicellular organisms like humans, cells integrate into tissues and organs. Some researchers argue that cells in such organisms don't need any kind of internal size-sensing mechanism. External controls, such as growth factors released by other cells, dictate how big a cell becomes.

To resolve the issue, some researchers are trying to determine if there are so-called checkpoints that prevent a cell from starting to divide if it isn't the right size. So far, the evidence for size checkpoints is contradictory and indirect. Cell biologists have attempted to find them by measuring an aspect of how individual cells enlarge—whether their growth is linear or exponential. For linear growth, a cell would enlarge at a constant rate until it divides. But for exponential growth, the increase would be proportional to the cell's girth. In the latter case, the small but natural variations in size between two cells resulting from division would rapidly expand to create a population of cells with large size differences. So if cells are growing exponentially, researchers reason, they must have a checkpoint to rein in growth and keep themselves within the observed narrow size range.

Determining what type of growth various kinds of cells actually undergo can be extremely difficult, however. The disparity in growth rates between a linearly growing cell and an exponentially growing one will be only about 6%, Kirschner notes.

Four years ago, cell biologist Alison Lloyd of University College London and colleagues gauged how quickly nervous system cells enlarged. Their results suggested that growth in these cells was linear. “Do mammalian cells have a checkpoint? We say no, the cell doesn't need it,” Lloyd says.

In a Science paper published 2 years ago (10 July 2009, p. 167), Kirschner and colleagues applied a statistical approach to reach the opposite conclusion about immune system cells. The next year, Kirschner teamed up with Scott Manalis of the Massachusetts Institute of Technology (MIT) and colleagues to weigh individual cells, herding them one by one onto the microscopic equivalent of a scale. Again, they found that the cells, which included bacteria and immune cells, displayed exponential growth, suggesting that checkpoints are operating. The identity of the molecules that detect the size of the cells remains unclear, however, Kirschner says.

His group and Lloyd's could both be right, Kirschner suggests: The two teams studied different kinds of cells that might behave differently. Umen agrees. Fast-growing immune cells might be more like yeast, relying on their own size-measuring mechanism, whereas nervous system cells mainly heed external cues, he speculates.

Although researchers have made some progress toward understanding how dividing cells sense and control their size, that issue is part of a broader question, says molecular biologist David Sabatini of MIT. Most of the cells in our bodies don't divide, yet they can continue to grow. How these cells sense when they are big enough to stop expanding is also a mystery, he says. Biologists who want to decipher cell size control still have some big questions to answer.

7. Mysteries of the Cell

# How Does the Cell Position Its Proteins?

1. John Travis

Somehow, a cell must get all its proteins to their correct destinations—and keep these molecules out of the wrong places. The mystery of how cells place their protein repertoire is far from solved.

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If you think air traffic controllers have a tough job guiding planes into major airports or across a crowded continental airspace, consider the challenge facing a human cell trying to position its proteins. The latest analyses suggest that some of our cells make more than 10,000 different proteins. And a typical mammalian cell will contain more than a billion individual protein molecules. Somehow, a cell must get all its proteins to their correct destinations—and equally important, keep these molecules out of the wrong places. While research addressing this challenge has already produced a Nobel Prize, biologists stress that the mystery of how cells place their protein repertoire is far from solved.

Protein localization within the cell wasn't always recognized as a fundamental puzzle. Before the advent of powerful microscopes and tools to label individual proteins, scientists typically considered cells simple bags of freely diffusing molecules. People were taught, says cell biologist James Wilhelm of the University of California, San Diego, “that the cytoplasm is a homogeneous goo.”

As organelles were discovered and specific proteins were found to be localized to them and to other cellular compartments, there came a need to explain how the molecules get to specific homes. Enter cell biologist Günter Blobel of Rockefeller University in New York City, who with colleague David Sabatini theorized in 1971 that proteins intended for the endoplasmic reticulum carried among their amino acids a localization, or sorting, signal. In work that won him a Nobel Prize in 1999, Blobel subsequently proved that conjecture, identifying sorting signals that direct newly synthesized proteins to various organelle membranes. “The concept that a sequence on a protein carried information relevant to its final destination was novel. … It was very speculative,” says cell biologist Karl Matlin of the University of Chicago, who is writing a history of that period.

Nobel Prize—case closed on protein localization? Not so fast. Many proteins operate outside organelles but still need to find specific homes or molecular partners within the relatively vast spaces of a cell. So does the cell have other ways to concentrate proteins in the right spots? Undoubtedly, biologists say. "The Blobel hypothesis in a sense kept blinders on people for a long time," notes developmental biologist Henry Krause of the University of Toronto in Canada. "The common perception was that proteins knew how to get places."

Biologists are finding other tricks cells use to place newly minted proteins, but another emerging story is that a cell begins to position proteins even before they are made. Starting in the mid-1980s, a few biologists began to gather evidence that cells localized proteins by directing the corresponding messenger RNAs (mRNAs) that encode their production to a specific destination, so the proteins are manufactured where they are needed. One of those pioneers, Robert Singer, now at Albert Einstein College of Medicine in New York City, initially showed that fibroblast cells position the protein beta-actin's mRNA to facilitate cell movement. Other scientists followed, revealing mRNA localization in fruit fly and frog eggs and in various animal neurons, for example. But a perception lingered that these cases were rare or oddities. “It was awfully lonely for a decade or so,” Singer recalls, noting that a meeting on mRNA localization he organized in 1994 drew only about 30 scientists.

There are seemingly obvious advantages to mRNA localization for positioning proteins. Efficiency, for example. Rather than requiring a cell to move many copies of a protein, Singer notes, “one mRNA could make thousands of proteins, and in the right place.” Localizing mRNAs could also prevent dangerous, unintended interactions as proteins move through a cell. “It seems easier to sort the information for a molecule than the molecules themselves,” Wilhelm says.

It's increasingly clear that cells agree with Wilhelm. He, Singer, and others point to a 2007 study by Krause's group as some of the first compelling evidence that mRNA localization is pervasive. In that work, the scientists labeled RNA with fluorescent tags and systematically observed the positioning of more than 3000 different types of mRNA during early fruit fly development. More than 70% exhibited clear localization. That's a “staggeringly large number,” Singer says. “It's almost as if every mRNA coming out of the nucleus knows where it's going.”

Thanks to this and similar work, many biologists are taking a new look at mRNA localization. And to an extent, history is repeating itself. Much as Blobel did with proteins, biologists are now identifying specific short RNA sequences—Singer calls them Zip Codes—that direct mRNA strands to various parts of the cell. Even proteins that have sorting signals of the type Blobel studied may also have mRNAs with built-in Zip Codes. “It looks like the RNA is localized first,” Krause says.

Krause suspects that cells needing to position proteins turn to RNA in additional ways. He speculates that certain RNA strands serve as focal points within the cytoplasm around which specific complexes of proteins form.

Clifford Brangwynne of Princeton University may have uncovered something along those lines while probing how cells position so-called P granules, poorly understood assemblages of proteins and RNA that help specify germ cells during development in nematodes. Once the fertilized worm egg breaks symmetry, P granules move to one half of the single-cell embryo, from which germ cells will arise. In 2009, Brangwynne reported that P granules behave like liquid droplets within cytoplasm—the drops can fuse to one another, drip out of dissected cells, and “wet” the surfaces of organelles such as the nucleus—and that specific RNA-binding proteins control localized “condensation” of these drops.

The biophysicist suspects that cells often use this strategy to condense RNAs and proteins into dynamic “microreactors” that encourage molecular interactions, perhaps between an enzyme and its substrate, for example. “People usually think about cellular organization being accomplished largely by membrane-bound compartments, which are bathed in a homogeneous cytoplasmic fluid,” he says. “The work by us and others in this area is beginning to paint a picture in which this cytoplasmic fluid is actually highly structured, which is useful for putting things in the right place at the right time.”

Cell biologist Timothy Mitchison of Harvard Medical School in Boston has recently collaborated with Brangwynne and found that nucleoli, RNA-protein bodies in a cell's nucleus, similarly represent such droplets. “It's fair to say Cliff has discovered a new state of biological matter,” he says.

It's clear that biologists have a long way to go before they fully understand the protein traffic control system within a cell. A Nobel Prize doesn't mean a mystery is solved, Blobel says with a laugh. “There's a lot left to be learned.”

8. Mysteries of the Cell

# How Do Hungry Cells Start Eating Themselves?

1. Mitch Leslie

Cell biologists might be close to learning where the internal membrane comes from that a hungry cell sprouts to encapsulate some of its contents and break them down for reuse.

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Hungry cells take recycling to the extreme. When a cell runs out of raw materials, it sprouts an internal membrane that encapsulates some of its contents and breaks them down for reuse. The process is called autophagy: literally, “self-eating.” Cell biologists have long wondered where this membrane comes from. Now, they might be close to an answer.

To devour part of itself, a cell initially fashions the equivalent of a mouth: a membrane pocket known as a phagophore. The expanding phagophore swallows a portion of cytoplasm, trapping proteins and even organelles such as mitochondria. After it closes, this membrane receptacle, now termed an autophagosome, docks with the cell's version of a stomach—the lysosome—which digests the delivery, recycling the material it contains.

Even in good times, when nutrients are plentiful, cells rely on autophagy to rid themselves of worn-out or defective organelles and molecules. More and more evidence suggests that when this self-cannibalism goes awry, cellular—and overall—health suffers. Faltering autophagy might promote a range of illnesses, from neurodegenerative disorders such as Huntington's disease to diabetes, and it could also spur aging.

Since researchers discovered autophagy in the 1950s, they've worked out many of its molecular details, but the origin of the autophagosome membrane has slipped through their grasp. And that's frustrating because determining where the membrane comes from could give a boost to researchers who hope to combat diseases by managing autophagy.

The autophagosome “wasn't following the rules,” says cell biologist Jennifer Lippincott-Schwartz of the National Institute of Child Health and Human Development in Bethesda, Maryland. Most organelles, she explains, hew to a “like from like” rule. A new mitochondrion, for example, is born when an existing one cleaves. But autophagosomes apparently don't spring from other autophagosomes.

That leaves two options. Proteins inside the cell could build the phagophore from scratch, synthesizing fresh membrane in the cytoplasm. Alternatively, the cell could borrow lipids from another location; membrane swapping among other organelles is common in cells. A cell teems with potential sources of existing membrane. The endoplastic reticulum (ER), a membranous network that helps synthesize proteins and lipids, pervades the cytoplasm, for example. Even the plasma membrane that wraps the cell could contribute to building the autophagosome.

Some recent work suggests that the ER, which manufactures most of the membrane lipids for the cell, donates membrane to nascent autophagosomes. A group from Finland and another group from Japan have observed autophagosomes or phagophores attached to the ER, as if they were being born. As one of the papers put it, a portion of the ER serves as a “cradle for autophagosome formation.”

However, other studies point to the Golgi apparatus, a membrane-rich organelle whose job is to put the finishing touches on new proteins from the ER, as the birthplace. Daniel Klionsky, a cell biologist at the University of Michigan, Ann Arbor, and colleagues revealed in Cell this summer that autophagy in yeast requires so-called SNARE proteins carried by membrane-enclosed capsules, or vesicles, released from the Golgi apparatus. These vesicles could supply fresh membrane to the growing phagophore. “We think the Golgi is a major source [of the lipids],” Klionsky says.

Lippincott-Schwartz's evidence backs yet another option. Famished mammalian cells obtain their autophagosome membrane from the outer membrane around mitochondria, she and her colleagues concluded last year in Cell. Using live cell imaging, the researchers watched fluorescently labeled autophagosomes grow right next to the outer mitochondrial membrane, and they appeared to be connected to the organelle. The team also followed tagged lipids appearing on mitochondria and then on autophagosomes.

Then there's the cell's plasma membrane, recently, and unexpectedly, implicated in autophagosome formation by David Rubinsztein of the Cambridge Institute for Medical Research in the United Kingdom and colleagues. The team's original goal was to track down the molecular partners of a protein present on young phagophores. They discovered that the protein latches onto another protein that helps engineer endocytosis, a process in which a cell imports material through pockets in the plasma membrane. That molecular link suggested that endocytosis feeds membrane to the autophagosome. When the researchers halted endocytosis, the number of autophagosomes in cells dropped by about 30%.

Five papers support four sources of autophagosome membrane—some people might call those results inconsistent. Yet many researchers say the field is moving toward an inclusive explanation. “What we have learned is that everybody was right,” says cell biologist Ana Maria Cuervo of Albert Einstein College of Medicine in New York City. In other words, the cell might draw material for the autophagosome membrane from many sources. That would make autophagosomes unique, with cells building essentially the same structure at several different locations. “There's no precedent for this kind of mechanism,” Klionsky says. “It's hard for people to digest,” Lippincott-Schwartz adds.

Why would a cell need multiple sources of autophagosome membrane? It could come down to supply. “There may be such a huge demand for membrane that you have to mobilize it from every place you can,” Klionsky says. Or cells might turn to different sources in certain situations. For instance, they might choose mitochondrial membrane when starving and ER membrane when they need to clean up the cytoplasm. Researchers say the field is poised to start answering questions like these. “I think that there will be a lot more clarity in the next few years,” Rubinsztein says.

9. Mysteries of the Cell

# Does a Gene's Location in the Nucleus Matter?

1. Elizabeth Pennisi

How the pattern of chromosomes and subnuclear bodies in the cell nucleus affects gene activity and other cellular functions is an enduring mystery in biology, one that won't be unraveled soon.

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Viewed under the right kind of microscope, a cell's nucleus resembles a plate of spaghetti. The noodles—chromosomes—appear to be tossed in Alfredo sauce. Yet the sauce is not a smooth cream but chunky, from a variety of subnuclear bodies, each with its own unique chemical makeup. And the randomness of each noodle's placement is an illusion, says Victor Corces, a cell biologist at Emory University in Atlanta. “The picture that is emerging is that the chef took a long time to arrange the spaghetti in a specific pattern.”

How that pattern in the nucleus and those subnuclear bodies affect gene activity and other cellular functions is an enduring mystery in biology, one that won't be unraveled soon. “We are at the very beginning of solving this problem,” Corces says.

Yet it's an important challenge. Changes in the structure within the nucleus may drive differentiation of cells. And in many diseases, including cancer, the nucleus becomes reorganized.

The first reports suggesting that the nucleus was more than a glob of chromosomes actually date back more than a century. Only in the past 2 decades, however, have new technologies begun to truly reveal the workings of its internal structures. The nucleus has compartments composed of RNA and proteins and designated places for each chromosome.

It stands to reason that all this order influences when and how genes work, but pinning down links between their activity and their location within the nucleus has for the most part eluded researchers' best efforts. “Cells seem to care about where DNA and proteins are within the nucleus,” says Jason Brickner, a cell biologist at Northwestern University in Evanston, Illinois. “The question is why and how.”

As early as 1885, Austrian biologist Carl Rabl suggested that chromosomes had designated spots in the nucleus. Not until a century later did German researchers Thomas and Christoph Cremer indirectly demonstrate the existence of these chromosome territories, as Rabl's contemporary Theodor Boveri dubbed them. And finally in 1988, a method to fluorescently label different chromosomes provided clear visual proof.

Many proteins inside the nucleus also have their designated homes. The nucleolus, a mass of proteins and RNA where the cell's ribosomes are made before export into the cytoplasm, was big enough to be seen with 19th century microscopes. But about a dozen other structures—Cajal bodies, speckles, paraspeckles, PML bodies, and more—populate the nuclear interior, new techniques developed over the past half-century have shown.

Several studies have indicated that the specific location of a gene in the nucleus makes a difference to its activity. In 2008, three groups showed that they could sometimes dampen or enhance the expression of different genes by tethering their DNA to the nuclear periphery. Other work has demonstrated that active genes generally tend to reside near the edges of chromosome territories, while silenced ones lie deep inside them.

A gene's location with respect to other DNA in the nucleus is also proving important to its activity. In 2002, Job Dekker at the University of Massachusetts Medical School in Worcester and colleagues developed a technology called chromosome conformation capture that has since revealed an extensive 3D network of chromosomal loops that bring distant genes and regulatory DNA into close proximity, possibly affecting gene expression.

A spate of recent techniques that allow researchers to follow the shifting locations of proteins and genes have begun to provide more clues to the importance of the internal structure of the nucleus. “We can also move things around in the nucleus and ask what effect does that have on gene expression,” says David Spector, a cell biologist at Cold Spring Harbor Laboratory in New York. Such work has led to an appreciation of the dynamics of the interior of the nucleus. Chromosomes, for example, can move about 0.5 micrometers in any one direction.

Yet for the most part, links between gene function and nuclear structure are still just correlations. A cell biologist may find that a gene is active if it's in a certain location in the nucleus or next to a certain body, but it's hard to say more than that at the moment. And as for diseases in which the structure of the nucleus is altered, “we need to determine if the changes in nuclear organization are a cause or a result” of a condition, Spector says.

Instead of controlling whether a gene is on or off, nuclear location may play a role in more fully activating a gene and making gene transcription and RNA processing more efficient, researchers suggest. A cell that can, say, activate its stress-response genes a little more quickly could have a survival advantage, favoring the evolution of specialized nuclear bodies that facilitate such efficiency.

To pin down the role of nuclear organization, “we have to do more in vivo biochemistry,” says Angus Lamond of the University of Dundee in the United Kingdom. Additional bodies and structures within the nucleus may also need to be isolated and characterized. And individual genes need to be better followed in living cells. These advances are on the horizon, biologists say.

“The field has made enormous progress in the past 20 or so years, and the technologies are now in place to allow us to really break this [field] open in the next 10 to 15 years,” Spector says. “It's a very exciting time in nuclear cell biology.”

10. Mysteries of the Cell

# Cell Biology's Open Cases

There are many mysteries that are likely to keep cell biologists working long hours, including how do cells know where they are, how do they sense chemical gradients, and how do they migrate together.

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Despite past cell biology success (see page 1048), Günter Blobel of Rockefeller University isn't content to rest on his laurels. In terms of the cell, “the number of things we don't know is staggering,” he says. The biologist is now tackling what he considers the “biggest mystery” in the cell: how the nuclear pore complex, which Blobel calls the cell's “largest and most versatile transport structure,” handles shuttling ions, proteins, RNAs, and ribosomes in or out of a nucleus. Below are a few more mysteries suggested to us that could keep cell biologists working long hours.

Where am I? In complex animals, cells specialize, forming many different tissues and cell types. But to behave appropriately, cells must know exactly where they are in a multicellular organism, and details of this cellular GPS are unclear.

By a nose. Many kinds of cells detect and migrate toward (or away from) tiny gradients of chemicals in their environment. How “cellular noses” operate with such sensitivity remains to be sniffed out in most circumstances.

Follow me. How do groups of cells migrate? Cell-cell adhesion often suppresses cell migration, but there are many instances in development and at other times when cells move en masse.

Complex question. After decades of work on the issue, cell biologists are still arguing about how newly synthesized proteins move across the membranes of the Golgi apparatus. Two main models dominate, but the technology needed to settle the question isn't quite ready.

The vault's secret. Still dismissed as unimportant by many biologists nearly 3 decades after their discovery in the cytoplasm of many kinds of cells, barrel-shaped protein particles dubbed vaults contain RNAs of unknown function inside. Like several other strange RNA-protein particles in the cell, what vaults do remains a riddle.

Long-distance chatter. Neurons project long axons to talk to distant colleagues, but biologists have observed in vitro that other cell types also create lengthy extensions, known by various names such as cytonemes or membrane nanotubes, to connect with distant cells. What these apparent links do remains unresolved (Science, 15 April, p. 312).

# Time to Adapt to a Warming World, But Where's the Science?

1. Richard A. Kerr

With dangerous global warming seemingly inevitable, users of climate information—from water utilities to international aid workers—are turning to climate scientists for guidance. But usable knowledge is in short supply.

DENVER, COLORADO—The people who brought us the bad news about climate change are making an effort to help us figure out what to do about it. As climate scientists have shown, continuing to spew greenhouse gases into the atmosphere will surely bring sweeping changes to the world—changes that humans will find it difficult or impossible to adapt to. But beyond general warnings, there is another sort of vital climate research to be done, speakers told 1800 attendees at a meeting here last month. And so far, they warned, researchers have delivered precious little of the essential new science.

At the meeting, subtitled “Climate Research in Service to Society,”* the new buzzword was “actionable”: actionable science, actionable information, actionable knowledge. “There's an urgent need for actionable climate information based on sound science,” said Ghassem Asrar, director of the World Climate Research Programme, the meeting's organizer based in Geneva, Switzerland. What's needed is not simply data but processed information that an engineer sizing a storm-water pipe to serve for the next 50 years or a farmer in Uganda considering irrigating his fields can use to make better decisions in a warming world.

Researchers preparing for the next international climate assessment, due in 2013, delivered some discouraging news for those striving to generate actionable science of use at the regional and local scale. But the challenges to the climate science community also include creating so-called climate services that can deliver actionable information effectively to users, speakers said. “We have a very long way to go,” Asrar noted.

## ISO actionable information

“How can we make decisions in changing times with uncertainty hanging over us?” asked David Behar, the San Francisco Public Utilities Commission's climate program director. “We need actionable science.” He defined that as “data, analysis, and forecasts that are sufficiently predictive, accepted and understandable to support decision-making.” More concisely, climatologist Bruce Hewitson of the University of Cape Town in South Africa said that a result is actionable science if you would spend your own money on it.

Behar said he finds the uncertainties surrounding actionable climate information “fairly overwhelming” these days. And he's having trouble coming up with intermediaries between users and scientists who can at least put the uncertainties into perspective without killing any motivation to act, he said. “It's a wild, wild West in the assessment world,” Behar said. “It's every man for himself.” “We're drowning in data,” Hewitson added, and “we're not very good at turning it into information.”

Too often the provider of climate information takes the attitude that “I've got the knowledge and you'll use it,” Hewitson said. Such take-it-or-leave-it approaches are part of the reason that only 30% or less of climate information offered is ever used, he said. And, he added, there is no example of an operation in Africa, at least, that is succeeding in the preferred approach of building effective communication between the climate research community and climate information users.

The situation is not much better in the United States, Behar said. In its fiscal year 2012 budget request, the National Oceanic and Atmospheric Administration (NOAA) asked for funds to support a reorganization that would create a National Climate Service (Science, 2 April 2010, p. 29). Such a service would more effectively deliver “easily accessible and timely scientific data and information about climate that helps people make informed decisions in their lives, businesses, and communities,” according to a NOAA web page.

While that proposal heads for the buzz saw that is money and politics in Washington, U.S. climate services reside in NOAA's Regional Integrated Sciences and Assessments (RISA) program. Through 10 regional operations variously called consortia, centers, programs, or partnerships, the RISAs support research addressing climate issues of concern to decision-makers. But the RISA centers “continue to struggle to meet demand,” Behar says. “It's still a struggle for users to know where to go.”

## Shaky science

Nascent climate services may be struggling to create the conduit between scientists and users, but they could use more quality product to fill that conduit. The great hope as a source for actionable information is regional climate modeling, but the meeting pointed up its many inadequacies. In a well-received plenary talk, Behar related a couple of discouraging anecdotes. The U.S. Environmental Protection Agency now requires water utilities to prepare for climate change before it will issue permits, he explained. So the utility Denver Water was interested in how much water might be flowing down to Denver from the mountains to the west as the world warms through this century.

To determine what a warmer world might hold for Denver, a group of organizations led by Denver Water took an economical approach. Embedding a detailed, regional climate model in a global model is expensive. Instead, the organization “statistically downscaled” climate projections for north central Colorado from 16 different global models previously run by others. Modelers assumed that local changes would be proportional to changes on the larger scales of a global model, and they adjusted local projections in accordance with how well model simulations of past climate had matched reality.

The statistical downscaling results for Colorado were mixed (see figure). All the models are showing warming, says Denver Water's climate scientist, Laurna Kaatz. “Precipitation, on the other hand, is all over the place,” she says. The region could get wetter or drier. And given the complexity of Colorado weather and climate, she adds, the more expensive model-within-model, dynamical approach might not have done any better. Besides, results from dynamical regional modeling have yet to show critics where, when, and how the approach is reliable (Science, 14 October, p. 173). And at the meeting, early results from the run-up to the next international assessment suggested there are no great improvements in the offing. Climate modeler Karl Taylor of Lawrence Livermore National Laboratory in California reported no progress over the past 5 years in narrowing the wide range in the sensitivity of climate models to added greenhouse gases.

## In the meantime

While they wait for stronger support, users are going with what they've got, uncertain as it is. David Nagel, executive vice president of BP America in Washington, D.C., told how BP is thickening the gravel patch under Alaska oil drilling rigs as retreating Arctic sea ice allows storm waves to grow higher. BP is also beefing up its infrastructure in Azerbaijan in the wake of long-term forecasts of increasing storminess. And slowly rising sea level has prompted BP to raise the height of drilling platforms in the North Sea.

Denver Water is developing scenarios: If this happens in climate, they posit, then here's the risk to your water supply, and here's how much the change will cost you if you don't prepare for it. Seattle Public Utilities asked Peter Gleick of the Pacific Institute in Oakland, California, about a quarter-billion dollars' worth of new storm drain pipes that would serve the city for up to 75 years. Gleick didn't know any more than anyone else how intense rain storms would become, but he was able to show the utility that increasing the size of storm drain pipes now would cost far less than being wrong about future rains.

To help get beyond the scenario mode of climate services, public organizations in and out of government are stepping forward. At the meeting, Craig Robinson of the National Science Foundation described how informed decision-making is one of four goals in the U.S. Global Change Research Program's draft 10-year strategic plan. Behar described the Societal Dimensions Working Group, which has invited him to become a member. It will strike up two-way communication between users and researchers developing one of the world's leading global climate models at the National Center for Atmospheric Research in Boulder, Colorado.

Behar also described Piloting Utility Modeling Applications (PUMA), a coalition of the five utilities of the Water Utility Climate Alliance and four RISAs. Within PUMA, state-of-the-art climate modeling would be identified for downscaling, uncertainties refined, and the need for climate services spelled out.

Universities are getting into the act as well. To develop and launch better ways to provide actionable environmental change information, said Antonio Busalacchi of the University of Maryland, College Park, UMD created a program called Climate Information: Responding to User Needs. The approach is in the style of the translational or “bench-to-bedside” approach used in medical research.

Most tenuously, speakers from the business community discussed the desirability of private climate services. Such businesses would develop and distribute climate information from data provided by a national climate service. That's how AccuWeather works: It takes data and forecasts from the National Weather Service to sell a presumably more useful product to the public and to business. Questions did arise about who could be trusted to project climate change—government or private enterprise—when, in contrast to forecasts in the weather business, no one can be proven right or wrong for decades.

“Can science save us?” asked one speaker. The answer running through the meeting was a guarded maybe—but only if someone can get usable science into the hands of decision-makers. And soon.

• * Open Science Conference of the World Climate Research Programme, 24–28 October, Denver, Colorado.

12. Archaeology

# Archaeologists Race Against Sea Change in Orkney

1. Sara Reardon

Coastal erosion, accelerated by climate change, is threatening the Orkney Islands' wealth of archaeology, but researchers are adapting to the changes

KIRKWALL, UNITED KINGDOM—Holding her jacket shut against the powerful wind, archaeologist Julie Gibson picks her way along the foot of a rock-studded cliff face on the western shore of the main island in north Scotland's Orkney archipelago. “I never know what I'm going to find when I come down here,” she says, brushing her fingers through the dirt at eye level to look for fragments of bone or pottery. “It's so different every time, all these new faces exposed on the cliff.” At her touch, bits of the soil crumble and fall away, loosened by storms that lash rain and waves up against the sandstone cliff and rapidly erode it.

As Orkney's county archaeologist, Gibson is one of the leaders in a charge to understand how erosion affects the islands' abundance of coastal archaeological sites. The cliff she's examining is only about 50 meters away from the incredibly well-preserved 5000-year-old Neolithic village of Skara Brae, a World Heritage site that draws 70,000 tourists per year and is a major source of income for the islands. The tight cluster of little round stone houses, complete with intact stone dressers, beds, and garbage heaps, has been an unparalleled resource for archaeologists like Gibson to learn how northern Britain's earliest agrarians lived.

Skara Brae looks safe at the moment, perched near the cliff edge overlooking the Bay of Skaill and protected by a 3-meter-high seawall. Yet powerful waves from just one violent storm could overwhelm the site's defenses and suck the village out to sea. “Even without anthropogenic global warming, Skara Brae's in trouble,” says archaeologist Caroline Wickham-Jones of the University of Aberdeen in the United Kingdom. “At some point, we're going to have to say, so be it.”

Hundreds of coastal sites from Orkney's 10,000-year human history are similarly endangered by climate change. Archaeologists can't fight the ocean so, like the people whose climate adaptation they study, modern researchers continue to adapt themselves. They take advantage of the fact that destructive storms can reveal and even excavate sites, though they're not the most delicate of diggers. And, by adopting new techniques such as 3D laser scanning, they can record, if not save, sites before they are taken by the sea. For Orkney, whose dense archaeology is covered with shell sand that preserves both stone and bone unusually well, the danger from storms and sea level rise are especially acute because of its northern latitude.

The history of Skara Brae is marked out by storms. In about 2200 B.C.E., a catastrophic storm drove the villagers away and blew masses of shell sand, called machair, over their houses, preserving them intact. Another massive storm, during a warm period in 1850, blew the sand off again and revealed the village to a local landowner, who excavated it himself. The village was originally well inland but during the centuries it lay buried, the sea rose more than 40 meters and turned a freshwater lake into the Bay of Skaill.

Now storms threaten it again. As waves ricochet about in the bay, Gibson explains, “you've got the full weight of the Atlantic piling into soft stuff, with hardly any resistance to sea taking back the sand.” That story is repeated all along northern coasts. Archaeologist Thomas Dawson of the University of St. Andrews in the United Kingdom estimates 50 meters of the coast on a beach in western Scotland was lost in a single night in 2005. “We were walking along the beach finding bits of human skulls and Iron Age pottery for weeks afterward,” he says. The Intergovernmental Panel on Climate Change predicts that in the future the North Atlantic will become stormier and storm surges may raise sea levels by 2 meters.

Local archaeologists say smaller storms are already accelerating erosion. “There's been more change [to the area near Skara Brae] in the last 10 to 15 years than in 100 years,” says archaeologist Jane Downes of Orkney College, part of the University of the Highlands and Islands here, as shown by historical maps and photos of the site. In the mid-1990s, a team from Orkney College excavated a butchery and garbage heap, or midden, close to the village, finding bones, beads, and other detritus that created a picture of the people's lifestyle. Today, that site is entirely gone, swept away by crashing waves that have scoured about 5 meters of coastline. “It's ferocious,” Downes says.

Letting nature take its course, or “managed retreat,” is now the approved method of dealing with coastal erosion, Dawson says. “Also called the do-nothing approach,” he adds. Seawalls tend to exacerbate erosion by redirecting the energy from the waves in unnatural ways.

There's only so long that researchers can mourn the loss of sites. “The fact is that they are [disappearing],” Downes says, “so rather than just bleating about it, it's much better to turn it into a positive.” Coastal erosion helps by exposing sites, taking what Gibson calls “sea bites” out of cliffs and providing peepholes into a layer cake of archaeology, the remnants of waves of settlers and invaders who built upon the same attractive spots. This can save a lot of digging but leaves very little time to decipher what's there.

On the small Orcadian island of Rousay, waves have been unearthing buried treasures along all of its beaches. Between rain showers, Rousay is haloed with multiple rainbows so vivid that it feels like you could drive beneath one. Archaeologist Ingrid Mainland of Orkney College squelches past several dozen sheep down a steep, grassy hill to the beach where she will inspect the remains of a 1000-year-old Iron Age building called a broch. Brochs, which were originally round stone towers several stories high, abound in northern Scotland, especially on Orkney. Built by late Iron Age people, it's still unknown whether they were defensive castles or summer homes for the wealthy.

“There's my broch.” Mainland points out a large grassy mound in what was her backyard while she was growing up on Rousay. Although the mounds make brochs clearly visible, researchers hesitate to excavate new ones both for lack of funds and fear of exposing them to the elements.

But in this case, coastal erosion did the work for them. Mainland points out a site on a beach called Swandro where, in July, researchers from the University of Bradford spotted the remains of what appeared to be a broch half-claimed by the sea. Waves had unearthed it at an angle, revealing that the lowest accessible part dated from 400 to 200 B.C.E. while the top part was remodeled as a Viking longhouse in the 1200s, says lead investigator Steven Dockrill. Because so much of the building had gone, the members of the team, which had only 3 weeks to work on the site, realized they may be able to get down to its base without much digging when they return next summer, Dockrill says. This will allow them, using modern technology for the first time, to sample the soil from the floor of a broch for bones and plant remains, perhaps settling the question of what brochs were used for.

A nearby graveyard contains both Viking boat burials and graves of Picts, a Scottish Iron Age people, suggesting possible conflict or mixing. If Vikings spent time in the Pictish broch, Dockrill hopes they left clues for his team to discover next year. That is, if the site is still there. Covered with a tarp weighted by stones, it lies only a few meters from the sea at high tide.

But even if the broch disappears before the team can finish its excavation, it has already given the researchers an opportunity to test out a new tool: a high-resolution 3D laser scanner that took a digital record of the site. The device needs only 30 minutes to scan across 270° out to a distance of up to 300 meters, allowing the archaeologists to slip onto a threatened site at low tide, quickly scan it, and slip out again.

“It's a godsend,” Gibson says. The speed of the scanner saves the team from the need to mark out a grid over the site with bits of string and meticulously record everything that is there, often while battling high winds and rain. Gibson hopes to use it extensively to monitor erosion season by season. Back in the lab, technicians overlay the 3D reconstruction onto high-resolution color photos also taken by the scanner. The detail is sufficient for researchers to see bits of the archaeology that have been eaten away “like a mad quarrier has been at it,” Gibson says, and watch for new pieces to pop out. The group plans to put this and future data online so that colleagues can read and analyze it.

“These sites are very emotive,” says architect Chris McGregor, who heads a team called the Scottish Ten—funded by the government agency Historic Scotland—that is systematically laser-scanning world heritage sites, preserving them as educational tools both online and for museums. One of their targets is the Heart of Neolithic Orkney site, which includes Skara Brae, a ring of standing stones called the Ring of Brodgar, and a Neolithic cairn called Maeshowe in which 12th century Vikings sheltered and left runic graffiti. Laser scanning, McGregor says, is useful for monitoring erosion as well as recreations for the public. “We could take you into Skara Brae's houses virtually,” he says.

Given the threat to sites around Scotland's coast, Historic Scotland has been running a “coastal zone assessment survey” since 1996, sending out surveyors to tramp more than 16,000 kilometers of coastline, record what's there, and send the data back for archaeologists to prioritize and make tough decisions about what to excavate, what to preserve, and what to abandon.

Dawson directs a group called Scottish Coastal Archaeology and the Problem of Erosion (SCAPE), which has been carrying out the survey for Historic Scotland since 2000. So far, the survey has inspected only 30% of Scotland's coastline and identified 11,500 archaeological sites. Its archaeologists recommended some kind of action on 3750 of these sites, be it excavation, laser recording, or other preservation—if the money is available. “This [huge number] is one reason you're not going to get people jumping up and down saying let's build coastal defenses,” Dawson says. To help prioritize, SCAPE has begun crowdsourcing: asking local communities to measure and photograph the state of erosion in an area. In return, communities have a say in which of their favorite beach sites get excavated.

When people get worried about climate change, Wickham-Jones says she wants to remind them that Orcadians have dealt with it for ages. Situated at the edge of an ice sheet that covered mainland Scotland, Orkney was particularly susceptible to sea level rise when the sheet melted at the end of the Ice Age. How ancient peoples dealt with a changing climate is one of the primary questions that archaeologists hope to answer by studying farming and migration patterns. “What do you do when you know your land is getting smaller around you?” Wickham-Jones asks.

The people of Orkney are grappling with similar problems today, although the current rate of sea level rise, about 2 millimeters per year, is a far cry from what people have often experienced in the past. But by studying ancient climate change and Orcadians' history of adaptation, “archaeology will start to pay dividends,” Gibson says. “Now we're trying to foretell what happens to ourselves.”