Feed the flab: The fat cells (stained red) that make up adipose tissue can’t grow without blood vessels (stained green) to nourish them. Zafgen, a startup based in Cambridge, MA, is developing obesity drugs that starve fat tissue by blocking blood-vessel proliferation. These drugs, which were originally designed to halt tumor growth, cause dramatic weight loss in obese mice. One of them will enter human clinical trials later this year.
Credit: David Burk, Pennington Biomedical Research Center

Drugs that block blood-vessel growth could tackle obesity

MIT Technology Review, July 15, 2009, by Jocelyn Rice  —  Both cancer and obesity kill hundreds of thousands of patients each year, but they have more than the Grim Reaper in common. Tumors and excess fat are both unhealthy accumulations of tissue that require elaborate networks of blood vessels to feed them. Now Zafgen, a biopharmaceutical startup based in Cambridge, MA, is attacking obesity the way that cancer researchers have been attacking tumors for decades: using drugs that interfere with its blood supply.

“It’s a very interesting and exciting concept,” says Rakesh Jain, director of the Edwin L. Steele Laboratory for Tumor Biology, at Massachusetts General Hospital, who has no ties to Zafgen. However, anti-angiogenic drugs such as Avastin, used to treat breast, lung, and colon cancer, have unpleasant side effects–especially when used long term–including problems with the reproductive, cardiovascular, and immune systems. “Their toxicity is manageable, but they are not innocuous agents,” says Jain.

Most pharmacological treatments for obesity have focused on controlling food intake. They attack weight gain centrally–in the brain–by trying to reduce appetite or encourage a feeling of satiety. But the neural mechanisms that regulate food intake also influence other physiological processes, says Zafgen president and CEO Thomas Hughes, meaning that this strategy is prone to producing side effects. Past weight-loss drug candidates have been discarded for their unwanted effects on mood, wakefulness, and reproductive function, and because their efficacy can wear off over time. “It’s kind of like a whack-a-mole game,” says Hughes. “You push down one thing, but something else pops up. That seems to be the nature of the way that circuits are wired in our brain.”

Instead, Zafgen aims to attack weight gain peripherally–in the fat tissue–which researchers hope will circumvent the side effects and rebound associated with more traditional approaches. “Conventional wisdom is that people become obese because they overeat,” says Hughes. “But the fact is that in an environment where people are exposed to the same food supply and lifestyle, some will gain weight and others will not.” In animals, those discrepancies seem to correlate with genetically determined differences among individuals’ fat tissue, he says. Animals with so-called hungry adipose–fat tissue with a strong propensity to expand–show different expression of genes that regulate blood-vessel formation than animals that are naturally lean.

Zafgen aims to alter those natural differences, effectively converting hungry adipose into its more benign cousin, thereby shrinking existing fat stores and preventing the accumulation of new ones. To do so, the company is investigating a class of small molecules originally designed to stop blood-vessel growth in tumors but abandoned due to their low performance. These agents attach to receptors in the lining of blood vessels, preventing the binding of factors that normally spur those vessels to proliferate. While these drugs proved ineffective for treating cancer, they might work for obesity, in which case simply shrinking fat tissue rather than completely eradicating it is sufficient.

In animal trials, obese mice treated with these repurposed drugs began to slim down after a few days and continued to shed fat at a precipitous rate until they reached a normal body weight, usually about three weeks later. This process was associated with a dramatic decrease in food consumption. But unlike drugs that cause weight loss by reducing food intake, these compounds seemed to reduce food intake by causing weight loss. As the fat cells shrank, they released free fatty acids that acted as a source of energy for the body, seeming to partially supersede the need for food calories. As soon as the animals reached a healthy weight, their food consumption returned to normal or even elevated levels, even though they continued to receive the drug. Nonetheless, the mice retained their new lean physiques for the remainder of the study–about six months total.

Not only did the mice lose weight, but they also became healthier overall. Their metabolic rate increased, their insulin sensitivity improved, and the fat content of their livers diminished. Within the fat tissue itself, there was a marked change in the number and architecture of blood vessels. Hughes says that all of these changes were highly reminiscent of those seen with extreme calorie restriction, which has long been known to improve health and extend life span in rodents. That makes sense, he says, because while the mice are actively losing weight, their calorie consumption plummets by as much as 80 percent.

Zafgen plans to start clinical trials on an anti-angiogenic molecule later this year, to determine whether the weight loss and health improvements seen in mice will translate to humans. Meanwhile, the company is working to better understand why the drugs it has tested are so potent in mice, and to discover new molecules with similar effects.

The rodent studies suggest that the doses sufficient for fat loss are lower than that required for tumor suppression, which might reduce the potential for side effects.

Hughes emphasizes that Zafgen intends its drugs to be used by the morbidly obese, and not by those trying to shed a pesky 15 pounds. “It’s serious medicine,” he says–not a lifestyle drug.


Back again: Schwann cells are shown here in a salamander limb. When the limb regrew after being amputated, only these cells wrapped around nerve fibers; other cell types did not turn into Schwann cells.
Credit: D. Knapp/E. Tanaka

Salamanders regrow limbs with less drastic cellular changes than previously thought.

MIT Technology Review, July 15, 2009, by Courtney Humphries  —  Salamanders have an enviable ability to regrow appendages that are amputated or injured; they re-create all the bones, muscle, skin, blood vessels, and nerves of the new body part so adeptly that it’s hard to tell that it was ever missing. Because of this ability, salamanders have been popular subjects for scientists studying regeneration–and trying to learn how human cells might be coaxed to perform the same feat.

In salamanders, new tissues come from a tumor-like mass of cells that forms at the site of the injury, called the blastema. Until now, most scientists thought that the blastema contained a population of stem cells that had become pluripotent–capable of giving rise to all the needed tissues. But a new paper in the journal Nature provides evidence that this is not the case. Instead, stem cells involved in regeneration only create cells of the tissue that they came from. The finding suggests that regeneration does not require cells to reprogram themselves as dramatically as scientists had assumed.

Elly Tanaka, lead scientist of the study at the Center for Regenerative Therapies, in Dresden, Germany, says that “a lot of people had the impression that these blastema cells were all the same.” Tanaka’s lab had even shown previously that a single muscle fiber could give rise to several types of cells in a regenerated limb. But previous studies, she says, relied on imperfect methods of tracking cells, such as using fluorescent dyes that may have leaked out to other cells.

In the latest study, Tanaka’s team employed a novel method for tracking the fate of cells from different tissues in a type of salamander called the axolotl. The researchers first created transgenic axolotls that carried green fluorescent protein (GFP) in their entire bodies. When the animals were still embryos, the researchers removed a piece of tissue from the limb region of the transgenic animals and transplanted the tissue into the same location in nontransgenic axolotls. The transplants were incorporated into the growing body as normal cells, and when the limb of the transplant recipients were then severed, the researchers could track the fate of the fluorescent cells as the limb regrew.

The researchers used this method to track the fate of cells of the inner and outer skin, muscles, and cartilage, as well as Schwann cells, which insulate nerve fibers. They found that, contrary to previous evidence, muscle cells at the amputation site only become muscle cells in the new limb. Other cell types also stuck to their previous identities; the only exception, Tanaka says, is that cells of the inner layers of skin and cartilage seem to be able to transform into one another. But for the most part, she says, the blastema is not a homogeneous mass of cells but “a mix of stem or progenitor cells from different tissues that stay separate during the whole process.”

The researchers also found that some cells remember not only their identities but also their position in the body. Cartilage cells, for instance, remember if they are supposed to form an upper arm, lower arm, or hand, while Schwann cells simply migrate anyplace that they are needed.

Tanaka says that the finding will provoke a major shift in thinking about the requirements of regeneration. In explaining why salamanders can regrow limbs and humans can’t, she says, “the hypothesis was that it’s because salamanders can powerfully alter the identity of cells.” But in fact, their cells never really lose their identities; instead, they seem to use tissue-specific stem cells capable of generating a certain part of the new limb. Tanaka points out that humans also have tissue-specific stem cells that replace different kinds of tissue. Perhaps salamanders “are not doing something much more complicated than what human stem cells would do,” she says. Coaxing human cells to regenerate might not require steps as drastic as making cells pluripotent.

Alejandro Sánchez Alvarado, a scientist who studies regeneration at the University of Utah School of Medicine, says that this method of “tattooing” the transplanted cells genetically is “a novel technique for the field of regeneration.” Tanaka believes that previous studies may have misled researchers by using imperfect tracking methods such as dyes by culturing cells before transplanting them and possibly altering them, or by allowing different cell types to contaminate samples.

Sánchez also says that the idea that blastemas held several different cell types was a “minority hypothesis” and that this study “shows that this hypothesis turns out to be correct.” He cautions that scientists now need to determine whether this phenomenon is the same in adult axolotls and in newts, which are a primary model organism for regeneration studies. But if the same mechanism turns out to underlie other cases of regeneration, it would change what scientists believe is required to regrow body parts, Sánchez says. But it leaves a major question unanswered: if humans already have tissue-specific stem cells, what exactly is the difference between our cells and those of salamanders?

HHS HealthBeat (July 15, 2009)

From the U.S. Department of Health and Human Services

 Diabetes can sneak up on you. It happens through pre-diabetes, when your blood sugar is elevated, but not high enough for a doctor to call it a sign of diabetes. That’s why a blood test is important. It can diagnose pre-diabetes, and give you time to do something to head off diabetes.

If you’re overweight or obese, the something can be losing weight. 

At the National Institute of Diabetes and Digestive and Kidney Diseases, Dr. Judith Fradkin says you don’t have to drop to your ideal body weight to dramatically reduce your risk of moving from pre-diabetes to diabetes.

[Dr. Judith Fradkin speaks] “Even losing an average of 15 pounds makes a huge difference in developing type 2 diabetes.”

That’s where proper eating and more physical activity can help.

Learn more at www.hhs.gov

HHS HealthBeat is a production of the U.S. Department of Health and Human Services


The New York Times, July 15, 2009, by Walecia Konrad  —  AFTER virtually disappearing for decades, bed bugs have made a comeback throughout the nation, with particularly bad infestations in densely populated apartment buildings.

Encouraged in part by the banning of DDT, the insects have become so prevalent that the Environmental Protection Agency held a National Bed Bug Summit in April.

Rather than wait for a Washington task force to do something, though, people with an infestation probably want to take immediate action. So this column is all about what consumers can do to avoid being bitten twice – first by the vermin and then by a venal exterminator.

While in most cases an infestation is more a skin-crawling nuisance than serious health problem, in some people severe reactions to bed bug bites can include asthma, generalized hives and even a life-threatening allergy attack that requires emergency treatment. Regardless of the medical consequences, though, bed bugs can be expensive to banish.

It’s not unusual for the typical afflicted family to spend $5,000 or more on inspections, exterminator fees, cleaning and storage, according to Jody L. Gangloff-Kaufmann, an urban entomologist with the New York State Integrated Pest Management program at Cornell University. Landlords of large apartment buildings have been known to spend as much as $80,000 to get rid of the pests, she said.

The insects, which are about the size of an apple seed and resemble ticks, are hard to detect and even harder to kill. The most successful efforts include a combination of a thorough cleaning and sorting, along with repeated professional applications of pesticides and other bed bug treatments.

But the bed bug boom has attracted fraudulent exterminators peddling money-wasting treatments that do not work. And because even reputable exterminators charge a wide range in prices and offer a variety of services, it can be hard to know what’s worth the money and what’s hype.

Here, then, is some calm advice from experts on what you can expect to spend and what you should – and shouldn’t – pay for.

IDENTIFYING THE PROBLEM Simply determining whether you have bed bugs can cost you money.

Small and nocturnal, the insects are hard to spot. They love to hide in mattresses and box springs, of course, but they also burrow in woodwork, night tables, picture frames, cushions and even behind outlet and light-switch covers. They come out only to feed on sleeping humans.

The most common way people discover they have bed bugs is when they wake up with bites. But only about a third of people react to bed bug bites, and many of those who do have reactions mistake them for mosquito bites. You may also get the same kind of bites from bird mites, says Gil Bloom, who is vice president of Standard Pest Management, an exterminating company in Queens, and director of public affairs for the New York State Pest Management Association.You can sometimes detect other evidence like bed bug feces, which look like tiny black specks, or blood stains from a bug that has just had a full meal.

If you suspect bed bugs, you’ll probably need a visual inspection from an exterminator to make sure. Many pest control companies do this free, hoping that if you have the bugs, you’ll hire them to do removal. Other companies may charge $50 to $200 to do a visual inspection.

Some companies use specially trained dogs that can sniff out bed bugs and their eggs. Well-trained dogs can be amazingly accurate, letting you know exactly where the bugs are so you can concentrate your efforts in those problem areas, says Jennifer Erdogan of Bell Environmental Services, a pest control company in Parsipanny, N.J., that uses two trained dogs, including Roscoe, a bug-sniffing beagle.

But the dogs’ services are expensive. You’ll pay $300 to $600 for a home inspection. If you go this route, ask about the dog’s credentials. You want to hear that the animal was trained at a certified facility that prepares dogs for jobs that include bomb and drug sniffing. FINDING AN EXTERMINATOR Counterintuitive as it may sound, you probably want to steer clear of pest control companies that emphasize their bed bug expertise. These may be one-person outfits or unqualified shops that have popped up in response to the epidemic.

Ms. Gangloff-Kaufmann advises finding an established company that has been in business at least five years and routinely battles all types of pests, including bed bugs.

Exterminators charge $250 to $900 a room to get rid of bed bugs, depending on the level of infestation and the types of treatments used. Some companies may charge by the bed if there are multiple people sleeping in the same room. Most exterminators use a combination of pesticides and steam heat.

Exposure to high temperatures is the only sure way to kill bed bugs, Ms. Gangloff-Kaufmann said. Cryonite, a freezing agent that kills bed bugs on contact, can add considerably to the cost of an exterminator visit, she said, and isn’t 100 percent effective against bed bugs.

Whatever an exterminator uses, it must directly contact a bed bug to kill it. Pesticides have no residual effect on bed bugs. That’s why you or your exterminator should never use bug bombs or foggers, which are completely ineffective with bed bugs.

Be sure your exterminator makes at least one follow-up visit. It’s virtually impossible to kill all the bugs in a given area with one treatment. Ask if any repeat treatments are included in the price quoted to you.

Check to see that the company you hire and the technician who is coming to your home are licensed in your state. To find your state’s licensing agency, check with the National Pesticide Information Center’s Web site, http://npic.orst.edu/state1.htm.

Also check the Better Business Bureau for any complaints filed against the exterminators you are considering.

ENCASE YOUR MATTRESS All bed bug experts agree that you must encase your mattress and box spring with a durable, leak-proof cover that will trap existing bugs inside the bedding and prevent new bugs from entering. (Even if you don’t currently suspect bed bugs, you might want to do this preventively, if you live in a highly infested area.)

The best covers are made from tightly woven cloth and have enclosed zippers and zipper locks to ensure there are no openings anywhere on the covering. A good cover will cost $70 to $150, depending on the size of your bed. Don’t bother with cheaper covers made of vinyl, which is uncomfortable to sleep on and is likely to crack and tear over time.

BEFORE YOU TOSS … Often, the first response to bed bugs is to throw stuff out. But replacing contaminated furniture, clothes and other possessions can be one of the biggest unnecessary bed bug expenses.

“Nothing kills bed bugs and their eggs better than high temperatures,” said Mr. Bloom, “so the dryer is your new best friend.”

Bedding, clothes, stuffed animals, backpacks and anything else you can fit into the clothes dryer can be decontaminated by 20 minutes on the high setting. Carry the items to the dryer in a cloth laundry bag that you can throw into the machine. If you use a plastic bag, discard it immediately; bed bugs or eggs might be lurking.

For items that can’t go in the dryer, consider packing them in plastic bins or bags and storing them for a year to make sure any hidden insects die.

For furniture and other large items, you may want to consider a professional fumigation service that will decontaminate the items away from your home and return them within a week or so. This can easily add $1,000 to your bed bug bill. But for antiques, heirlooms and other hard-to-replace items, it may well be worth the cost.


Humans in space: Astronaut Heidemarie M. Stefanyshyn-Piper performs space-station maintenance during the Shuttle Endeavour‘s visit to the ISS in late 2008.   Credit: NASA 

Independent review of human-spaceflight plans gets under way today.

MIT Technology Review, July 17, 2009, by Anne-Marie Corley  —  A 10-person committee charged with reviewing the future of U.S. human spaceflight will hold its first public meeting today, beginning a process that must cover a lot of territory in very little time.

The independent panel of experts will examine NASA’s Constellation Program, which plans to send humans to the International Space Station (ISS), the moon, and possibly Mars, and will consider alternatives to options already on the table.

The review comes at a time when the Space Shuttle is facing retirement, and a new launch system, called Ares, isn’t scheduled to begin operations until at least 2015, leaving a gap in U.S. launch capability of five years or more. NASA’s Constellation Program has attracted criticism for the Ares design, as well as for slipping timelines and budget overruns.

In a speech at MIT last week, John Holdren, director of the White House Office of Science and Technology Policy, outlined three key questions that the panel will examine: whether it’s possible to reduce the gap in launch capability, what the options are for extending the use of the ISS beyond 2016, and what a timetable for missions beyond low-earth orbit (LEO) might look like, given budget constraints.

It is notably an “advice only” committee: it will analyze options and present recommendations but will not determine the future of human spaceflight. “We’re not being asked to pick the direction,” says Edward Crawley, Ford Professor of Engineering at MIT and one of the 10 panelists. “That’s why the president gets paid the big bucks. We just give him the list of options.”

The committee will report its findings to the Obama White House, Holdren, and a new NASA administrator: retired astronaut Charles Bolden is currently awaiting confirmation hearings. The panel’s report is expected by the end of August in order to affect an administration decision on the way forward, before the 2010 financial-year budget is set.

Dubbed the “Augustine committee” for its chair, Norman Augustine, a retired chairman and CEO of Lockheed Martin and a former member of the President’s Council of Advisors on science and technology for Bill Clinton and George W. Bush, the panel includes former astronauts, industry executives, engineers, and experts on the civil space program. A NASA review team will provide technical support to the committee.

John Logsdon, who served on the Columbia Accident Investigation Board and was founder and former director of the Space Policy Institute at George Washington University’s Elliott School of International Affairs, says that the panel was well chosen, with “people that can do in-depth technical analysis, that have years of experience and reputations for integrity.”

But a key question that many analysts and proponents of human spaceflight are asking is what the committee members will actually focus on.

The technical background of the panel, says Logsdon, equips the members to examine the current Constellation Program. Criticism of the Constellation “architecture,” particularly the design of the Ares launch system, which requires separate rockets for crew and cargo, cropped up during President Obama’s NASA transition-team investigations. The question was whether this architecture or those based more heavily on existing technologies could be built faster and more cheaply. According to Logsdon, that criticism prompted the transition team to recommend that before the president “embraces” the current architecture, he get an independent judgment on whether it’s the right one. “And that’s what this panel is set up to do,” Logsdon says.

The committee’s evaluation may also step outside of NASA’s current budget. Scott Uebelhart, a member of MIT’s Space, Policy and Society research group, who coauthored a white paper outlining potential goals of human spaceflight earlier this year, says that the question is whether the panel really has “carte blanche” to choose the best plans regardless of cost, or if it will be told, “Here’s the budget, tell us what you can do with it.”

Meanwhile, in a bill set to go to the House of Representatives today, the House Appropriations Committee has cut $700 million from the Obama administration’s requested $3.9 billion for the Constellation Program’s fiscal-year 2010 budget, which leaves the program at 2009 funding levels, pending the recommendations of the Augustine committee. While the administration will likely submit an amended budget request once it hears the panel’s results, Uebelhart says that this “time-out” sends mixed signals about the breadth of the Augustine charter.

Alternative technologies that the panel may consider are the primarily DOD-funded Evolved Expendable Launch Vehicle (EELV), based on already-existing rocket launchers like Atlas and Delta, and an option called Direct, based on existing Space Shuttle components.

The panel will also debate a balance of human missions with robotic ones. These could involve precursors to moon or Mars missions that set the stage for human exploration, as opposed to purely robotic missions. Other issues include opportunities that exist for international collaboration and how to further stimulate commercial spaceflight capability–NASA has already issued contracts to two space companies, SpaceX and Orbital Sciences, to bring cargo to the ISS. The panel must also consider whether the United States should stay involved with the ISS beyond 2015. “You cannot just go back to the moon and utilize the space station at the same time on the same projected budget,” says Logsdon. “You have to give up goals, schedule, or increase the budget.”

However, without the power to evaluate human spaceflight against other space priorities, such as Earth observation satellites or orbiting space science telescopes, it remains uncertain how the panel’s results will fit into a comprehensive plan for future spaceflight. With a budget that’s tightening on all fronts, the administration and Congress will have to figure out how much NASA can afford to do safely after the committee completes its review.

Still, Crawley believes that the panel’s influence will be significant. “There are times and places where these groups can make an impact,” he says. “At the beginning of an administration, with a high-ticket item like the space program, there’s a lot of influence.” Logsdon agrees that the panel is “absolutely crucial to NASA’s future and the country’s future in space.”

Another former astronaut, Jeff Hoffman, adds, “They need a policy [on human exploration beyond Earth]. You can’t just cut the budget and push things further and further into the future, because eventually it will just fall apart. So they need a decision, what do they want to do, what do we want to do as a nation, and I think the Augustine committee will have big input on that.”


Courtesy of Yulin Chen and Z. X. Shen  —  A diagram of how electrons flow without resistance on the surface of of bismuth telluride.

Stanford University News, July 17, 2009, by Shawne Workman  —   Physicists at the SLAC National Accelerator Laboratory and Stanford University have confirmed the existence of a type of material that could one day provide dramatically faster, more efficient computer chips.

Recently predicted and much sought, the material allows electrons on its surface to travel with no loss of energy at room temperatures and can be fabricated using existing semiconductor technologies. Such material could provide a leap in microchip speeds, and even become the bedrock of an entirely new kind of computing industry based on spintronics, the next evolution of electronics.

Physicists Yulin Chen, Zhi-Xun Shen and their colleagues tested the behavior of electrons in the compound bismuth telluride. The results, published online June 11 in Science Express, show a clear signature of what is called a topological insulator, a material that enables the free flow of electrons across its surface with no loss of energy.

SLAC is a U.S. Department of Energy laboratory, managed by Stanford.

The discovery was the result of teamwork between theoretical and experimental physicists at the Stanford Institute for Materials and Energy Science (SIMES), a joint SLAC-Stanford institute.

In recent months, SIMES theorist Shoucheng Zhang and colleagues predicted that several bismuth and antimony compounds would act as topological insulators at room temperature. The new paper confirms that prediction in bismuth telluride. “The working style of SIMES is perfect,” Chen said. “Theorists, experimentalists and sample growers can collaborate in a broad sense.”

The experimenters examined bismuth telluride samples using X-rays from the Stanford Synchrotron Radiation Lightsource at SLAC and the Advanced Light Source at Lawrence Berkeley National Laboratory. When Chen and his colleagues investigated the electrons’ behavior, they saw the clear signature of a topological insulator. Not only that, but the group discovered that the reality of bismuth telluride was even better than theory.

“The theorists were very close,” Chen said, “but there was a quantitative difference.” The experiments showed that bismuth telluride could tolerate even higher temperatures than theorists had predicted. “This means that the material is closer to application than we thought,” Chen said.

This magic is possible thanks to surprisingly well-behaved electrons. The quantum spin of each electron is aligned with the electron’s motion-a phenomenon called the quantum spin Hall effect. This alignment is a key component in creating spintronics devices, new kinds of devices that go beyond standard electronics. “When you hit something, there’s usually scattering, some possibility of bouncing back,” explained SLAC theorist Xiaoliang Qi. “But the quantum spin Hall effect means that you can’t reflect to exactly the reverse path.” As a dramatic consequence, electrons flow without resistance. Put a voltage on a topological insulator, and this special spin current will flow without heating the material or dissipating.

Topological insulators aren’t conventional superconductors nor fodder for super-efficient power lines, as they can only carry small currents, but they could pave the way for a paradigm shift in microchip development. “This could lead to new applications of spintronics, or using the electron spin to carry information,” Qi said. “Whether or not it can build better wires, I’m optimistic it can lead to new devices, transistors and spintronics devices.”

Fortunately for real-world applications, bismuth telluride is fairly simple to grow and work with. Chen said, “It’s a three-dimensional material, so it’s easy to fabricate with the current mature semiconductor technology. It’s also easy to dope-you can tune the properties relatively easily.”

“This is already a very exciting thing,” he said, adding that the material “could let us make a device with new operating principles.”

The high quality bismuth telluride samples were grown at SIMES by James Analytis, Ian Fisher and colleagues.

SIMES, the Stanford Synchrotron Radiation Lightsource at SLAC and the Advanced Light Source at Lawrence Berkeley National Laboratory are supported by the Office of Basic Energy Sciences within the Department of Energy Office of Science.



Xiao-Liang Qi. (Photo by Lauren Schenkman.)  

New work by condensed-matter theorists at the Stanford Institute for Materials and Energy Science at SLAC National Accelerator Laboratory points to a material that could one day be used to make faster, more efficient computer processors. In a paper published online Sunday in Nature Physics, SIMES researchers Xiao-Liang Qi and Shou-Cheng Zhang, with colleagues from the Chinese Academy of Sciences and Tsinghua University in Beijing, predict that a room temperature material will exhibit the quantum spin Hall effect. In this exotic state of matter, electrons flow without dissipating heat, meaning a transistor made of the material would be drastically more efficient than anything available today. This effect was previously thought to occur only at extremely low temperatures. Now the race is on to confirm the room-temperature prediction experimentally.


Shou-Cheng Zhang. (Photo by Lauren Schenkman.)  

Zhang has been one of the leading physicists working on the quantum spin Hall effect; in 2006 he predicted its existence in mercury telluride, which experimentalists confirmed a year later. However, the mercury telluride had to be cooled by liquid helium to a frigid 30 millikelvins, much too cold for real-world applications.

In their hunt for a material that exhibited the quantum spin Hall effect, Zhang and Qi knew they were looking for a solid with a highly unusual energy landscape. In a normal semiconductor, the outermost electrons of an atom prefer to stay in the valence band, where they are orbiting atoms, rather than the higher-energy conduction band, where they move freely through the material. Think of the conduction band as a flat plain pitted with small valence-band valleys. Electrons naturally “roll” down into these valleys and stay there, unless pushed out. But in a material that exhibits the quantum spin Hall effect, this picture inverts; the valence-band valleys rise to become hills, and the electrons roll down to roam the now lower-energy conduction band plain. In mercury telluride, this inversion did occur, but just barely; the hills were so slight that a tiny amount of energy was enough to push the electrons back up, meaning the material had to be kept extremely cold.

When Zhang, Qi and their colleagues calculated this energy landscape for four promising materials, three showed the hoped-for inversion. In one, bismuth selenide, the theoretical conduction band plain is so much lower than the valence band hills that even room temperature energy can’t push the electrons back up. In physics terms, the conduction band and valence band are now inverted, with a sizeable difference between them.

“The difference [from mercury telluride] is that the gap is much larger, so we believe the effect could happen at room temperature,” Zhang explained.

Materials that exhibit the quantum spin Hall effect are called topological insulators; a chunk of this material acts like an empty metal box that’s completely insulating on the inside, but conducting on the surface. Additionally, the direction of each electron’s movement on the surface decides its spin, an intrinsic property of electrons. This leads to surprising consequences.

Qi likens electrons traveling through a metal to cars driving along a busy road. When an electron encounters an impurity, it acts like a frustrated driver in a traffic jam, and makes a U-turn, dissipating heat. But in a topological insulator, Qi said, “Nature gives us a no U-turn rule.” Instead of reversing their trajectories, electrons cruise coolly around impurities. This means the quantum spin Hall effect, like superconductivity, enables current to flow without dissipating energy, but unlike superconductivity, the effect doesn’t rely on interactions between electrons.

Qi points out that, because current only flows on their surfaces, topological insulators shouldn’t be seen as a way to make more efficient power lines. Instead, these novel compounds would be ideal for fabricating tinier and tinier transistors that transport information via electron spin.

“Usually you need magnets to inject spins, manipulate them, and read them out,” Qi said. “Because the current and spin are always locked [in a topological insulator], you can control the spin by the current. This may lead to a new way of designing devices like transistors.”

These tantalizing characteristics arise from underlying physics that seems to marry relativity and condensed matter science. Zhang and Qi’s paper reveals that electrons on the surface of a topological insulator are governed by a so-called “Dirac cone,” meaning that their momentum and energy are related according to the laws of relativity rather than the quantum mechanical rules that are usually used to describe electrons in a solid.

“On this surface, the electrons behave like a relativistic, massless particle,” Qi said. “We are living in a low speed world here, where nothing is relativistic, but on this boundary, relativity emerges.”

“What are the two greatest physics discoveries of the last century? Relativity and quantum mechanics.” Zhang said. “In the semiconductor industry in the last 50 years, we’ve only used quantum mechanics, but to solve all these interesting frontier problems, we need to use both in a very essential way.”

Zhang and Qi’s new predictions are already spurring a surge of experiments to test whether these promising materials will indeed act as room-temperature topological insulators. 

“The best feedback you can get is that there are lots of experiments going on,” he said.

-Lauren Schenkman
SLAC Today, May 12, 2009

A new form of silicon could create cheaper photo detectors that are easier to make in bulk.                               

MIT Technology Review, July 15, 2009, by Anne-Marie Corley  —  A material dubbed black silicon has shown great promise for making cheaper, more sensitive light detectors and imaging devices, while potentially taking advantage of established silicon manufacturing methods. But one of black silicon’s key characteristics–a forest of microscopic cones that form on its surface and give the material its black color–may not be as important as it first appeared to be. The Harvard University researchers who first discovered black silicon are now studying a modified form of the material that has no cones but exhibits the same unique optoelectronic properties. Because of its faint coloring, the new stuff is nicknamed pink silicon, although it can barely be distinguished from a regular silicon wafer.

Black silicon was discovered accidentally by a team led by Harvard physics professor Eric Mazur. The group created the material by throwing together a gaseous sulfur compound and a silicon wafer in a vacuum, then blasting the silicon with a femtosecond laser to restructure it on the nanoscale.

Black silicon can absorb light over a wider spectrum than can normal silicon–from low-frequency visible light through near- and short-wave-infrared wavelengths that would normally pass right through regular silicon. Another property, called photoconductive gain, gives black silicon much greater sensitivity to light. These properties have identified black silicon as a way to make smaller, cheaper, and lighter silicon-based light detectors and to replace more expensive materials used in infrared detectors found in fiber-optic links, security systems, and elsewhere.

But the cones that cover the surface of black silicon, which are created during the high-intensity, short-pulse femtosecond laser restructuring of silicon, can cause problems–for example, by foiling bulk fabrication attempts. James Carey, who studied the properties of black silicon while a grad student in Mazur’s lab at Harvard and cofounded the company SiOnyx, based in Beverly, MA, to commercialize the material, explains that it’s harder to mass-produce wafers with tall cones in a foundry process. This is because a foundry uses thin-film deposition steps, so contact with cones can interfere with smooth processing through the plant. There’s also a risk that the cones could break off. “New materials are hard to introduce to a foundry process with no problems,” Carey says. The cones also interfere with attempts to study the material’s electronic properties in greater detail, because they increase the material’s surface area by one to two orders of magnitude, making it scatter electrons more readily.

Mazur’s lab has now added a new twist to the black-silicon production process, taking advantage of the absorption and high-gain properties of black silicon but keeping the material completely flat. That could help overcome fabrication challenges and allow for more detailed study of the material.

The breakthrough came when the researchers saw “flatter” black silicon cones after changing the parameters of their laser during experiments. It turned out that there were actually two things going on in their original laser production process: ablation, which was responsible for creating the surface cones, and rapid melting combined with resolidification, which trapped doped sulfur atoms in a nanocrystalline structure of the silicon. Both of those processes occurred together originally, but Mazur’s lab has now separated them. “Once we posed the question, it was pretty straightforward to test it,” says Mark Winkler, the grad student who first noticed the strange effects. “It just took changing the way we thought, from taking it as a given that we make spikes to asking how much control we have over the material that we’re making.”

Laser ablation requires a higher energy than melting, so the researchers tuned the intensity of their laser to hit below the ablation threshold but above the melting threshold. Now the laser breaks down the material and lets it recrystallize with 1 to 2 percent sulfur atoms trapped inside–highly doped for a semiconductor–but the surface remains smooth and flat. While the cones no longer form–causing the surface to look slightly pink, instead of black–the material still absorbs straight through to the infrared spectrum.

Without the cones, Mazur says, “we’re finally doing measurements that were impossible” previously, including measuring carrier densities, electron mobility, and other electronic properties. Mazur adds that it’s also easier to study the chemical composition of the substrate and “get a nice profile” of the material below the surface. The big question still remaining, says Winkler, is why black silicon absorbs light in the infrared spectrum in the first place.

Meanwhile, SiOnyx is busy turning black silicon’s potential into commercial devices. While the company’s process doesn’t use completely flat silicon, the SiOnyx researchers cut down the cone height from microns to about 200 nanometers, Carey says, to help the fabrication process. SiOnyx recently completed its first successful foundry run using the shorter cones, thus demonstrating their capability for bulk manufacturing. The company hopes to have commercial photo detectors ready to go this year.

Richard Myers, of Radiation Monitoring Devices, a research and commercial development company that has done some research with black silicon, says that the advantage of the material is that it expands silicon’s functionality. “It comes down to low cost and existing processing technology,” Myers says. The silicon electronics infrastructure is cheap and “in place,” so the new material–whether black or pink–is useful as another way that people are trying to push the limits of silicon.