Reprogrammed Human Cells Shed Light on Rare Disease

A new study uses induced pluripotent stem cells to investigate a neurological disease and test drugs.

By Courtney Humphries

Stem cells generated from patients with a rare neurological disorder are helping scientists dissect the underlying mechanism of the disease and test several candidate drugs. The study, published today in Nature, is the realization of one of the major goals in stem cell research: using induced pluripotent stem (iPS) cells--stem cells derived from reprogrammed adult cells--to study the effects of disease in a patient's own cells, which are otherwise impossible to access.

Mirroring disease. By taking skin cells from patients with a rare neurological disease, researchers were able to create stem cells that could be turned into the specific neurons (shown here labeled with red and blue markers) affected by the disease. Credit: Gabsang Lee and Lorenz Studer.

The work is "a blueprint for the future of using stem cells to study and treat neurological disease," says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute. (Loring was not involved in the study.)

The idea is simple: Take skin cells from patients with a particular disease, turn those cells into stem cells, direct those stem cells to become a cell type of interest--for instance, the dopamine-releasing neurons that are affected by Parkinson's disease--and see how those cells behave and react to different drugs. A spate of recent papers has demonstrated the development of disease-specific stem cells for conditions such as Down syndrome, amyotrophic lateral sclerosis, spinal muscular atrophy, and Parkinson's disease. The new study is the first to use cells derived from iPS cells to test drugs for their effect against a disease.

Lorenz Studer, lead author of the paper and a developmental biologist at the Sloan-Kettering Institute in New York, and his team focused on a rare disease called familial dysautonomia (FD), which affects neurons that control functions such as the sensation of touch, blood pressure and tear flow. Symptoms usually arise early in life, sometimes from birth, and include a lack of muscle tone and reflex control, problems sensing pain, high blood pressure and difficulty breathing. The disease is caused by a known genetic mutation, but scientists have been unable to create an animal model of the disease.

The researchers obtained skin cells from patients with FD and created lines of iPS cells by inserting four genes into the cells using viruses. This reprogrammed the cells to behave like embryonic stem cells, which can give rise to all cell types. The researchers then directed those undifferentiated cells to turn into specific cell types, including the neural crest cells that give rise to the neurons affected by FD.

FD patients are known to have a mutation in a gene that encodes a protein called IKAP. The mutation causes part of the genetic sequence to be skipped when the gene is translated into a protein; however, the genetic defect only affects certain tissues, for reasons not known. To understand more about the disease, the researchers looked for the normal and mutated protein in the different cell types. Studer says they expected that the neural cells would have more of the abnormal protein. But in fact, they found that the faulty translation happened at equal rates in the different types of cells. Levels of normal IKAP were much lower in the neural cells, which may be why the disease strikes these cells.

The team also found that the cells were defective in their ability to differentiate into neurons and did not migrate as easily as normal cells in a culture dish. The researchers used these differences to measure the effect of three drugs that had been proposed as candidate drugs for FD. One of them, kinetin, a natural plant hormone that is often used as an antiwrinkle treatment in cosmetics, showed promise in treating the cells When cells were treated with the drug, Studer says, "it led to near complete reversal of the splicing defect." Further treatment reversed the defect in differentiation, although it did not affect the cells' ability to migrate.

Susan Slaugenhaupt, a neurologist at Massachusetts General Hospital who studies FD, says that these cells help alleviate a long-standing frustration in studying neurological disease. This technology provides "the ability to examine disease-relevant cell types from patients" for the first time, she says. "You can't get brains from patients and look at these cell types." Slaugenhaupt is now collaborating with the research team to further test drugs for FD using this model.

Slaugenhaupt adds that this study is the first to show that kinetin can improve disease in neural cells and that it "provides the best evidence to date that long-term treatment with kinetin may be beneficial to FD patients." Clinical trials of the drug are scheduled to start soon.

http://www.technologyreview.com/biomedicine/23288/

TR35 2009 Young Innovator

Kevin Fu, 33

University of Massachusetts, Amherst

Defeating would-be hackers of radio frequency chips in objects from credit cards to pacemakers

Stepping back: Kevin Fu takes the point of view of a malevolent hacker to uncover dangerous security flaws in wireless devices. Credit: Steve Moors

Multimedia Watch Fu explain how he uncovers security flaws.

Could implanted medical devices that use wireless communication, such as pacemakers, be maliciously hacked to threaten patients' lives? Kevin Fu is no stranger to such overblown scenarios based on his research, though he prefers to stick to talking about technical details. But Fu, a software engineer and assistant professor of computer science, is a security guy. And security people think differently.

"Anyone who works in the world of security--they always have an adversary in mind," Fu explains, sitting behind his desk on the second floor of the UMass Amherst c­omputer science building. "That's how you can best design your systems to defend against it."

The threats Fu researches are chiefly those connected to the security of radio ­frequency identification, or RFID. RFID is an increasingly common technology, used in everything from tags for shipping containers to electronic key cards, from Exxon­Mobil's Speedpass key-chain wands to Chase's no-swipe "Blink" credit cards. It allows billing and personal information to be shared quickly and wirelessly. But not, Fu realized back in 2006, very securely.

After testing more than 20 such "smart" or no-swipe credit cards from MasterCard, Visa, and American Express, Fu and his colleagues found that they could lift account numbers and expiration dates from several of the cards--even cards inside a wallet--just by walking past them with a homemade scanner.

Criminals troll mailboxes, shopping malls, and airports, harvesting nearby RFID information for use in identity-theft scams. Basically, they pick your pocket without ever touching your pocket. Making these cards truly secure would require good encryption software--Fu's specialty. But encryption requires a steady supply of energy, something that the passive, externally powered RFID chips used in these applications don't have. "The inspiration was about the programming," Fu explains. "But the programming won't work without an RFID computer to program. And the RFID computer won't work without solving the energy issues." He breaks a weary smile. "So, thus far, it's been something like a two-year sideline."

The only way for Fu to resolve this catch-22 is to invent new technology--a project he's working on with a team led by Wayne Burleson, a professor of electrical and computer engineering. But even as he wrestled with this problem, Fu found himself wondering, as only a security guy can: if financial information is vulnerable, what about seemingly more obscure targets with far bigger consequences?

This is what first brought him to the heart-attack machine.

At his desk, Fu clicks through a ­Power­Point slide show of bad-guy examples, from the madman who put cyanide-laced Tyleno­l on Chicago drugstore shelves in 1982 to the hacker who posted seizure-inducing animations on an Internet message board for epileptics.

"It might seem paranoid," Fu admits, "but from a security standpoint, you need to start with the fact that bad people do exist." And there seemed no better place to hunt such misanthropes than the world of medicine.

Fu began wondering about the security of medical devices that use RF communication, such as pacemakers and defibrillators. He discussed the problem with his longtime colleague Tadayoshi Kohno, assistant professor of computer science and engineering at the University of Washington and a veteran investigator into the vulnerabilities of computer networks and voting machines (see TR35, September/October 2007).

"Kevin is a fantastic researcher," Kohno says. "His research is now covered in almost every undergraduate computer-security course that I know of. And his insights are exceptionally deep." Together, Fu and Kohno took their questions about de­fibrillators far from the computer ­science lab--into the world of cardiologist William H. Maisel, director of the Medical Device Safety Institute at Boston's Beth Israel Deaconess Medical Center.

The two explained to Maisel's wide-eyed staff how security people think. In turn, the medical professionals introduced the security researchers to Cardiology 101--starting with pacemakers and defibrillators, devices that are implanted in some half-million people around the world every year. Basically, a pacemaker regulates aberrant heartbeats with gentle metronomic pulses of electricity, while a defibrillator provides a big shock to "reboot" a failing heart. Merged, they form an implantable cardioverter defibrillator, or ICD. The ICD is designed to stop a heart attack in a cardiac patient. But, Fu and Kohno wondered, could it create one instead?

In his UMass office, Fu pulls out a shoebox containing the works of an ICD. It looks the way the Tin Man's heart might: padlock-sized and encased in hard, silvery surgical steel, now peeled away can opener-style. I instinctively reach in, drawn like a magpie to the shiny objects. Fu quickly jerks the box away. "Um, you don't want to touch that," he says. "The coil in these things delivers 700 volts"--enough juice to stop your heart.

He points out the matchbook-sized microchip and antenna coil--technolog­y that connects the latest-generation ICDs with the Internet, allowing doctors to re­program a device without surgery. From the perspective of cardiologists and patients, this wireless programming is a godsend. But from Fu's viewpoint, it represents a new security risk. And so he wondered: Could black-hat hackers listen in on the wireless communication between an ICD and its programming computer? Could they make sense of what they heard and use it to inflict harm?

"Most people who make these devices don't think like this," Fu says. "But this is how the adversary thinks. He doesn't play your game; he makes his own game." To assess the security threat, the researchers needed to play the hacker's game.

Catching bugs: By exposing ways for wireless devices to be hacked, Fu has alerted manufacturers to the potential dangers that their customers face. He found that implanted cardiac devices are particularly vulnerable.
Credit: Steve Moors

Fu's team set out to create a technique to eavesdrop on defibrillator chatter. The hardware was just off-the-shelf stuff--a platform designed to allow researchers and serious hobbyists to build their own software radios. It has been made into FM radios, GPS receivers, digital te­levision decoders--and RFID readers. All that was left was to write the software, rip the antenna coil out of an old pacemaker, solder it into the radio--and voilà, they had a transmitter.

"It worked pretty well--amazingly well," Fu says. After "nine months of blood and sweat," they could intercept digital bits from an ICD--but they had no idea what those bits meant. His students trudged back to the lab to figure out how to interpret them. Using differential analysis--basically, changing one letter of a patient's name and then listening to how the corresponding radio transmission changed--they were able to painstakingly build up a code book.

Now their homemade software radio could listen in on and record ICD programming commands. The device could also rebroadcast those recordings, as fresh commands, to any nearby ICD. It had become dangerously capable of playing doctor.

Fu discovered one set of commands that would keep an ICD in a constant "awake" state, surreptitiously draining the battery to devastating effect. "We did a back-of-the-envelope calculation on this," he explains. "A battery designed to last a couple years could be drained in a couple weeks. That alone was a notable risk."

Even more notable, Fu's software radio was capable of completely reprogramming a patient's ICD while it was in his or her body. The researchers were able to instruct the device not to respond to a cardiac event, such as an abnormal heart rhythm or a heart attack. They also found a way to instruct the defibrillator to initiate its test sequence--effectively delivering 700 volts to the heart--whenever they wanted.

Fu doesn't like to think of himself as h­aving built a heart-attack machine, or even of discovering that such a thing could be built. Though he is an academic who doesn't shy away from pursuing real-world applications for his theoretical technologies, that "real world" is usually at least 10 years in the future. But the ramifications of the ICD-programming radio were both immediate and chilling: the device could be easily miniaturized to the size of an iPhone and carried through a crowded mall or subway, sending its heart-attack command to random victims.

A heart-attack machine? Really? It would be foolish, Fu says, not to recognize that there are depraved people out there, more than capable of building and using such a machine to inflict harm on random innocents "just for kicks." To this extent, the issue of protecting remote programming access to ICDs is directly related to the issue of protecting RFIDs. Encrypting the communication is the only way to shield millions of people from random risks. It doesn't take a Fu to come up with practical solutions, but by exposing the security dangers he has provided a valuable, perhaps even life-saving, alert to manufacturers.

Fu is too smart to engage in speculation about how the technology could be abused, except to say that he'd be very surprised if there weren't "people already working on this." In the best case, we'll never know how foresighted he was; medical-device maker­s will eliminate the threat before hackers ever exploit it. "Kevin is a computer scientist who also has the ability to look at problems like a medical doctor and like a patient," says Maisel. "The work Kevin is doing now--relating to medical-device security and privacy--has the potential to impact millions of people."

How about the more dramatic scenario­s? Imagine a spy agency using printed circuitry to put a heart-attack machine into a news­paper, delivered with morning coffee to a foreign leader with a pacemaker. Or a Lex Luthor-like supervillain who retrofits a radio tower to broadcast his death ray to entire populations.

Kevin Fu--professor, researcher, scientist--rolls his eyes. "All I can say about that one," he says with a laugh, "is it might make a pretty good movie." --Charles Graeber

http://www.technologyreview.com/TR35/Profile.aspx?trid=760

Wi-Fi via White Spaces

A network design that uses old TV spectrum could produce better long-range wireless connectivity.

By Erica Naone

Long-range, low-cost wireless Internet could soon be delivered using radio spectrum once reserved for use by TV stations. The blueprints for a computer network that uses "white spaces," which are empty fragments of the spectrum scattered between used frequencies, will be presented today at ACM SIGCOMM 2009, a communications conference held in Barcelona, Spain.

White spaces: Accessing the Internet over unused portions of TV spectrum could provide good long-range connectivity in rural areas, and help fill in gaps in city networks. Microsoft researchers tested a new protocol, called White Fi, using the device shown here. Credit: Microsoft Research

TV stations have traditionally broadcast over lower frequencies that carry information longer distances. However, with the ongoing transition from analog to digital broadcasts, more unused frequencies are opening up than ever.

By tapping into these lower frequencies, it should be easier to provide broadband Internet access in rural areas and fill in gaps in city Wi-Fi networks. For example, the spectrum between 512 megahertz and 698 megahertz, which was originally allotted to analog TV channels from 21 to 51, offers a longer range than conventional Wi-Fi, which operates at 2.4 gigahertz. "Imagine the potential if you could connect to your home [Internet] router from up to a mile," says Ranveer Chandra, a member of the Networking Research Group at Microsoft Research behind the project.

The FCC ruled last November that companies could build devices that transmit over white spaces but also gave strict requirements that this should not interfere with existing broadcasts, both from TV stations and from other wireless devices that operate within the same spectrum. Chandra and his colleagues designed a set of protocols, which they call "White Fi," to successfully navigate the tricky regulatory and technical obstacles involved with using white spaces.

"It's a totally different paradigm for wireless networking," says Chandra. "Until now, in wireless networks, you were given a spectrum, and you would share it with everyone else. Everyone was an equal stakeholder. Now, you have this spectrum where there are certain people who are primary users."

One of the main obstacles for Chandra's group was dealing with a network of different devices; in the past, work focused on sending and receiving signals between individual devices over white spaces.

Setting up a group of devices to communicate over white-space frequencies is a more complicated proposal, because white-space devices have to find available spectrum, which can change depending on where and when the device is operating. The researchers designed a system consisting of a wireless access point, like the router used in Wi-Fi networks, and the mobile devices communicating with it.

White Fi is designed so that each device measures the spectrum conditions around it and works with the others to find available frequencies. Because interference can happen at any time, the system can move to a different slice of spectrum if need be.

Some of the challenges that faced the group came about because of the undefined nature of white-space frequencies. . The researchers designed their algorithms to determine the ideal amount of frequency bandwidth to use for a broadcast, balancing the desire for strong signal against the possibility of interference with neighboring frequencies. They also had to design a way for mobile devices to find a signal from an access point.

One of the most important parts of the White Fi system is a protocol for dealing with collisions among different signals (particularly those from wireless microphones, which can turn on at any time). Even a single packet of interference is enough to produce audible disruptions for a microphone. Even if interference affects only one device on the network, strict regulations forbid all devices on the network from using that channel. The researchers got around this by designing the access point so that it maintains a backup channel. If another user is detected, the white-space device or access point immediately switches to the backup channel, which reassigns bandwidth use as needed.

Peter Steenkiste, a professor of computer science at Carnegie Mellon University who specializes in networking, says that previous work on white spaces has focused on addressing one problem at a time. "The thing that I think is very interesting about this paper is that it really has looked at how you put a complete system together," he says.

Steenkiste adds that "there are a lot of practical issues that they've worried about." In particular, he says, the researchers did not assume an ideal, controlled environment for their system. Rather, they took into account such problems as measurement "noise" and the unpredictable behavior of wireless microphones. "[The research] has an answer for every question," Steenkiste says.

Chandra says that his group recently received an experimental license from the FCC that allows them to build a prototype White Fi system on the Microsoft Research Campus in Redmond, WA. They plan to send their findings to the FCC in the hope that the data will help determine future white-space regulations. Chandra notes that since the transition from analog to digital television is happening worldwide, there is a high level of international interest in US white-space experiments. Researchers and companies all over the world are looking for technologies to take advantage of the fragments of spectrum that will open up in the coming years, he says.

http://www.technologyreview.com/communications/23271/?a=f

Bone-setting Glue

A new adhesive, inspired by aquatic worms, could help repair shattered bone.

By Lauren Gravitz

Shattered bones pose a difficult problem for surgeons, who currently must use tiny screws and plates to hold fragments in place long enough for the break to heal. But a new glue, which has the sticking power to adhere to bone, could one day help orthopedic surgeons fix difficult breaks, researchers announced today at the American Chemical Society conference in Washington, DC.

King of the castle: Sandcastle worms (shown here), which build themselves a house of sand, inspired a novel adhesive that could one day be used to glue broken bones back together. Credit: Fred Hayes

Multimedia See how the worms inspired the medical adhesvie.

Making glue that sticks to bone and other wet surfaces has proven a particularly complex task--either it slides right off, or it dissolves into the surrounding liquid. Russell Stewart, lead researcher and biomedical engineer at the University of Utah, found his inspiration for the glue in the tiny sandcastle worm. The worm builds its tube-shaped home on the ocean floor using sand grains and bits of shell, cemented into place piece by piece like brick and mortar.

"The worm has to overcome several problems when putting a sandcastle together underwater," Stewart says. "Its adhesive has to adhere to wet surfaces, and when it's secreting that adhesive under water, it has to prevent it from just dissolving into the ocean." Although the glue starts out as fluid, it must harden into a solid. "The worm has solved all of these problems, and we're trying to copy those solutions," he says.

Stewart and his colleagues found that the sandcastle worm uses changes in pH level to trigger the glue to harden. Inside the worm, where the pH is low, the glue is a fluid. Exposure to seawater, which has a higher pH, slowly causes the glue to solidify. After a little tinkering, the researchers recreated a synthetic version of the worm's adhesive--a polyacrylate glue that is water soluble but doesn't dissolve in liquid, is at least as strong as Super Glue, and is twice as strong as the worm's original glue. Cell culture experiments showed no sign of toxicity; early tests in rats appear to back that up and also show no unusual immune reaction.

"There's a significant need in the clinic for better glues," says Jeffrey Karp, a biological and chemical engineer at Brigham and Women's Hospital in Boston. And while there are some very strong medical grade glues available, he notes that they also tend to be highly inflammatory. The need for an adhesive that can bond bone and align small fragments without inflammation is a pressing one. What's more, Karp says, the new adhesive is unique in that it can be applied to a wet surface without migrating away from the injury site. "Glues tend to be very messy, and surgeons have great difficulty manipulating them in wet environments," he says. "It's difficult to place them directly on the site of interest."

A close bond: A scanning electron microscope image of two glass beads cemented together by a sandcastle worm and removed from the worm's tube (inset). The larger image is a close-up of the connection, which was made using the worm’s adhesive. Credit: Russell Stewart

Stewart and his colleagues believe the adhesive can be used as a complement to wires, pins, and plates--large pieces could be held in place with hardware, while small pieces could be glued back in. And in cranial-facial fractures, where using pins and screws can cause permanent cosmetic damage, the glue could potentially be injected with a syringe, avoiding open surgery.

"One of our challenges is to hold very small pieces in very precise alignment. We just need to hold them there until they heal, just six weeks," says Thomas Higgins, an orthopedic surgeon at the University of Utah's School of Medicine who specializes in joint fractures and has consulted with Stewart on the adhesive's clinical applications. "To have something that is liquid and would assume a more rigid state when you put it [in the body], that would be much more easily applicable and much more versatile than what we use now," he says. "This is still preliminary, but it shows a lot of promise."

Beyond bonding bones, the adhesive holds promise for a number of wet-environment applications--everything from mending cracked teeth to repairing corrosive cracks on ships out of dry dock. "It will be really interesting for a dentist or orthopedic surgeon to consider [this type of material] as a strategy for bone and tooth repair," says Herbert Waite, a biochemist at the University of California, Santa Barbara who was not involved in the research.

Karp notes that there's still a lot of work to be done. "Just the idea of forming glue in the presence of blood may be very different than forming it under seawater or under lab conditions," he says. But he believes that the group is off to a good start. "I think it's a really interesting and novel approach, to better understand the biology of the sandcastle worm to create new adhesives," Karp says. "Evolution is the best problem solver. There's nothing that can compete with it."

http://www.technologyreview.com/biomedicine/23270/

A Lunar Nuclear Reactor

Tests prove the feasibility of using nuclear reactors to provide electricity on the moon and Mars.

By Brittany Sauser

Researchers at NASA and the Department of Energy recently tested key technologies for developing a nuclear fission reactor that could power a human outpost on the moon or Mars. The tests prove that the agencies could build a "safe, reliable, and efficient" system by 2020, the year NASA plans to return humans to the moon.

Generating power: A power-conversion unit consisting of two Stirling engines, sitting opposite each other, is set up for testing at NASA’s Marshall Space Flight Center. Pumped liquid metal is used to transfer heat from the reactor to the engines, where it is converted to electricity. Credit: NASA

A fission reactor works by splitting atoms and releasing energy in the form of heat, which is converted into electricity. The idea for using nuclear power in space dates back to the late 1950s, when they were considered for providing propulsion through Project Orion. In the 1960s a series of compact, experimental space nuclear reactors were developed by NASA under the Systems Nuclear Auxiliary Power program. But public safety concerns and an international treaty banning nuclear power in space stopped development.

Now nuclear power is being considered for lunar and Mars missions because, unlike alternatives such as solar power, it can provide constant energy, a necessity for human life-support systems, recharging rovers, and mining for resources. Solar power systems would also require the use of energy storage devices like batteries or fuel cells, adding unwanted mass to the system. Solar power is further limited because the moon is dark for up to 14 days at a time and has deep craters that can obscure the sun. Mars is farther away from the sun than either the Earth or the moon, so less solar power can be harvested there.

The new nuclear power system is part of a NASA project started in 2006, called Fission Surface Power, that is examining small reactors designed for use on other planets. While nuclear power remains controversial, the researchers say that the reactor would be designed to be completely safe and would be buried a safe distance from the astronauts to shield them from any radiation it would generate.

The recent tests examined technologies that would see a nuclear reactor coupled with a Stirling engine capable of producing 40 kilowatts of energy--enough to power a future lunar or Mars outpost.

"We are not building a system that needs hundreds of gigawatts of power like those that produce electricity for our cities," says Don Palac, the project manager at NASA Glenn Research Center in Cleveland, OH. The system needs to be cheap, safe, and robust and "our recent tests demonstrated that we can successfully build that," says Palac.

To generate electricity, the researchers used a liquid metal to transfer the heat from the reactor to the Stirling engine, which uses gas pressure to convert heat into the energy needed to generate electricity. For the tests, the researchers used a non-nuclear heat source. The liquid metal was a sodium potassium mixture that has been used in the past to transfer heat from a reactor to a generator, says Palac, but this is the first time this mixture has been used with a Stirling engine.

"They are very efficient and robust, and we believe [it] can last for eight years unattended," says Lee Mason, the principal investigator of the project at Glenn. The system performed better than expected, Palac says, generating 2.3 kilowatts of power at a steady pace.

Cooling off: Marc Gibson, a NASA test engineer, inspects the radiator panel used to cool the fission power system that is being tested at Glenn Research Center. The panel is six feet by nine feet. Twenty such radiators would be needed for a full-scale system. Credit: NASA

The researchers also developed a lightweight radiator panel to cool the system and dissipate the heat from the reactor. The prototype panel is approximately six feet by nine feet--one-twentieth the size required for a full-scale system. Heat from a water-cooling system is circulated to the radiator where it dissipates.

The researchers tested the radiator panel in a vacuum chamber at Glenn that replicates the lack of atmosphere and the extreme temperatures on the moon--from over 100 degrees Celsius during the day to below 100 degrees Celsius at night. The panel dissipated six kilowatts of energy, more than expected--a "very successfully test," says Palac. On the moon, the panel must also survive the dusty environment cause by the regolith.

Lastly, the researchers tested the performance of the Stirling alternator in a radiation environment at Sandia National Laboratories in Albuquerque, NM. The objective was to test the performance of the motor, ensuring that the materials would not degrade. The alternator was subjected to 20 times the amount of radiation it would expect to see in its lifetime and survived without any significant problems.

Mason says that the tests are very important in showing the feasibility of the system and that the next step is for the researchers to conduct a full system demonstration, by combining a non-nuclear reactor simulator with the Stirling engine and radiator panel. He says that these tests should be completed in 2014.

The researchers are also working on the power transmission and electronics of the system. "A lunar base needs lots of power for things like computers, life support, and to heat up rocks to get out resources like oxygen and hydrogen," says Ross Radel, a senior member of the technical staff and part of the advanced nuclear concepts group at Sandia. His group is working on the systems dynamic analysis, a computer model that predicts how the reactor will perform during testing. "Nuclear is a stepping stone to move further out into manned space exploration," says Radel.

"It is a fascinating project and the only possible method of providing power for a manned trip to Mars," says Daniel Hollenbach, a researcher in the nuclear science and technology division at Oak Ridge National Laboratory, who was not involved in the project.

Mason says that nuclear fission is one of a number of concepts being tested as a power source for human missions to the moon and Mars, and if selected, he says the technology could be deployed by 2020.

http://www.technologyreview.com/energy/23247/

Energy-Aware Internet Routing

Software that tracks electricity prices could slash energy costs for big online businesses.

By Will Knight

An Internet-routing algorithm that tracks electricity price fluctuations could save data-hungry companies such as Google, Microsoft, and Amazon millions of dollars each year in electricity costs. A study from researchers at MIT, Carnegie Mellon University, and the networking company Akamai suggests that such Internet businesses could reduce their energy use by as much as 40 percent by rerouting data to locations where electricity prices are lowest on a particular day.

Data beast: Google maintains a huge datacenter in The Dalles, OR. Credit: John Nelson

Modern datacenters gobble up huge amounts of electricity and usage is increasing at a rapid pace. Energy consumption has accelerated as applications move from desktop computers to the Internet and as information gets transferred from ordinary computers to distributed "cloud" computing services. For the world's biggest information-technology firms, this means spending upwards of $30 million on electricity every year, by modest estimates.

Asfandyar Qureshi, a PhD student at MIT, first outlined the idea of a smart routing algorithm that would track electricity prices to reduce costs in a paper presented in October 2008. This year, Qureshi and colleagues approached researchers at Akamai to obtain the real-world routing data needed to test the idea. Akamai's distributed servers cache information on behalf of many large Web sites across the US and abroad, and process some 275 billion requests per day; while the company does not require many large datacenters itself, its traffic data provides a way to model the demand placed on large Internet companies.

The researchers first analyzed 39 months of electricity price data collected for 29 major US cities. Energy prices fluctuate for a variety of reasons, including seasonal changes in supply, fuel price hikes, and changes in consumer demand, and the researchers saw a surprising amount of volatility, even among geographically close locations.

"The thing that surprised me most was that there was no one place that was always cheapest," says Bruce Maggs, vice president of research at Akamai, who contributed to the project while working as a professor at Carnegie Mellon and is currently a professor at Duke University. "There are large fluctuations on a short timescale."

The team then devised a routing scheme designed to take advantage of daily and hourly fluctuations in electricity costs across the country. The resulting algorithm weighs up the physical distance needed to route information--because it's more expensive to move data further--against the likely cost savings from reduced energy use. Data collected from nine Akamai servers, covering 24 days of activity, provided a way to test the routing scheme using real-world data. The team found that, in the best scenario--one in which energy use is proportional to computing--a company could slash its energy consumption by 40 percent. "The results were pretty surprising," Maggs says.

The ability to throttle back energy consumption could have another benefit for massive Internet companies, the researchers say. If an energy company were struggling to meet demand, it could negotiate for computation to be moved elsewhere; the researchers say that the market mechanisms needed to make this possible are already in place.

Follow the money: This map, compiled by Pingdom.com, shows the location of Google's US datacenters. Credit: Google

Spiraling energy consumption has become a major concern for the world's largest Web companies; a report published by McKinsey & Company and the Uptime Institute in July 2008 estimates that datacenter energy usage will quadruple during the next decade in the absence of efforts to improve efficiency.

The pressure to reduce costs and curb emissions is forcing datacenter managers to radically rethink design and management. Google recently built a datacenter in Belgium that relies entirely on ambient cooling--on days when the weather gets to warm, the center's servers are simply shut down. Maggs says that an energy-aware Internet-routing scheme is an extension of this idea. "Resources are getting more fungible and this is the ultimate extension of that," he says.

"In principle this could work," says Jonathan Koomey, a staff scientist at Lawrence Berkeley National Laboratory and a consulting professor at Stanford University, who studies information technology energy use and environmental impact. "The trick is to be able to control these systems well enough and to create controls that are cheap enough to be able to take advantage of the arbitrage opportunity available from differential electricity prices, without affecting reliability or latency," says Koomey.

Maggs cautions that the idea is not guaranteed to reduce energy usage or pollution, only energy costs. "The paper is not about saving energy but about saving cost, although there are some ways to do both," he says. "You have to hope that those are aligned."

Furthermore, he warns that the scheme relies on companies' hardware having some sort of "energy elasticity." In other words, their servers need to use substantially less power when idle than when running full tilt. This has not always been the case, but Google says that its custom servers consume 65 percent of the normal power when idle.

Michael Manos, senior vice president of Digital Realty Trust, a company that designs, builds, and manages large datacenters, believes that the lack of elasticity currently built into modern hardware makes it impossible to achieve the improvements suggested.

"It is great research but there are some base fundamental problems with the initial assumptions, which would prevent the type of savings they present," Manos says. Because most servers aren't used to capacity, he says, "you just can't get there."

However, Manos does see plenty of room for improvement in datacenter designs. "I believe the datacenter industry is just beginning to enter into a Renaissance of sorts," he says. "Technology, economic factors, and a new breed of datacenter managers are forcing change into the industry. It's a great time to be involved."

Koomey suggests that spiraling energy costs could encourage some companies to consider radical steps such as rerouting data: "Electricity use is a big enough component of data-center costs that this just might work."

http://www.technologyreview.com/business/23248/

The Smallest Laser Ever Made

Surface-plasmon lasers could enable a new generation of computers based on nanophotonics.

By Katherine Bourzac

Researchers have demonstrated the smallest laser ever, consisting of a nanoparticle just 44 nanometers across. The device is dubbed a "spaser" because it generates a form of radiation called surface plasmons. The technique allows light to be confined in very small spaces, and some physicists believe that spasers could form the basis of future optical computers just as transistors are the basis of today's electronics.

Tiny laser: This simulation shows the intensity of light around a new type of laser, called a spaser, when operating in a plasmon-producing mode. The concentration of plasmons is most intense at the gold sphere that makes up its core. The inner black circle indicates the position of the sphere, which is coated with a dye-embedded silica shell, marked by the outer black line. Credit: Nature

While the best consumer electronics operate at speeds of about 10 gigahertz, Mikhail Noginov, professor of physics in the Center for Materials Research at Norfolk State University in Norfolk, VA, notes that optical devices can operate at hundreds of terahertz. Optical devices are, however, difficult to miniaturize because photons can't be confined to areas much smaller than half their wavelength. But devices that interact with light in the form of surface plasmons can confine it within much tighter spots.

"There's currently a big effort, mostly theoretical, towards designing a new generation of nanoelectronics based on plasmonics," says Noginov. Unlike other previous plasmonic devices, spasers are an active element that can produce and amplify these waves. Noginov co-led the development of the new spaser with Ulrich Wiesner of Cornell University and Vladimir Shalaev and Evgenii Narimanov of Purdue University. The work is described today in the journal Nature.

The spaser made by Noginov and his collaborators consists of a single nanoparticle just 44 nanometers in diameter, with different parts that perform functions analogous to those in a conventional laser. In a normal laser, photons bounce between two mirrors through a gain medium that amplifies the light. The light in a spaser bounces around on the surface of a gold sphere in the nanoparticle's core in the form of plasmons.

The challenge, says Noginov, is to make sure that this energy does not dissipate rapidly from the metal surface. His team accomplished this by coating the gold with a layer of silica embedded with dye. This layer acts as a gain medium. Light from the spaser can remain confined as plasmons or it can be made to leave the particle surface as photons in the visible-light range. Like a laser, the spaser must be "pumped" to supply the necessary energy. Noginov's group accomplishes this by bombarding the particle with pulses of light.

The size of a conventional laser is dictated by the wavelength of the light it uses, and the distance between the reflective surfaces can't be smaller than half the wavelength of the light--in the case of visible light, about 200 nanometers. The "beauty" of the spaser is that it gets around this limitation by using plasmons, says Noginov. Spasers could probably be made as small as one nanometer. Any smaller than that, Noginov explains, and the nanoparticles' functionality breaks down.

Noginov and his collaborators are not the first to make a nanolaser. This July, researchers led by Cun-Zheng Ning, professor of electrical engineering at Arizona State University, and Martin Hill of Eindhoven University in the Netherlands created a nanolaser about 100 nanometers wide, using different materials. Ning and Hill's nanolaser was the first to overcome the wavelength constraints on the size of lasers. The work published today, however, is the first example of a spaser.

"The spaser works about a thousand times faster than the fastest transistor, while having the same nanoscale size," says Mark Stockman, professor of physics at Georgia State University. "This opens up the possibility to build ultrafast amplifiers, logic elements, and microprocessors working about a thousand times faster than conventional silicon-based microprocessors."

Stockman predicted the phaser in 2003 with David Bergman, professor of physics at Tel Aviv University in Israel. The creation of the spaser, says Bergman, "is a beautiful piece of work."

Spasers are likely to find their first application not in optical computing but in places where conventional lasers are used today, says Noginov. Indeed, "a more near-term application is in the magnetic data-storage industry," says Sakhrat Khizroev, professor of electrical engineering at the University of California, Riverside, who is also developing nanolasers. The magnetic data-storage media used for today's hard disks are reaching their physical limits; one way of extending its capabilities is to heat the media with very small spots of light during recording, which could be done with nanolasers, says Khizroev. However, the researchers caution, any applications are probably years away.

http://www.technologyreview.com/computing/23249/?a=f