Radiation Therapy for Moving Targets

Researchers have combined two devices for real-time tumor tracking and treatment.

By Katherine Bourzac

Normal tissue often gets caught in the crossfire during radiation therapy. Damage is caused by the high-energy beams of radiation used to kill tumor tissue--particularly when the patient's breathing causes the tumor to shift.

Odd couple: A prototype device combines a magnetic resonance imager with a linear accelerator, two technologies that ordinarily interfere with each other. The blue cylinders facing each other are the imaging magnets. The metal circle visible to the left at the back is a magnetic and radiation shield that protects the accelerator’s waveguide. Credit: University of Alberta Cross Cancer Institute

To better track a tumor's position in real time and adjust the radiation accordingly, researchers at the University of Alberta in Canada have combined a linear accelerator with a magnetic resonance imager. Today in Anaheim, CA, at the annual meeting of the American Association of Physicists in Medicine, researchers will present evidence that a device that combines these technologies can accurately track and irradiate a moving target.

Radiation therapy uses high-energy x-rays from a medical linear accelerator to damage tumor tissue and treat nearly every type of cancer. In the United States, half of all patients with cancer receive this form of treatment, which typically requires 10 to 15 sessions lasting from about 15 to 30 minutes each. In order to make sure the entire tumor is irradiated, doctors have to irradiate a margin of healthy tissue around it, which leads to side effects including nausea, pain, and skin-tissue damage. In between sessions, the healthy tissue regenerates, but the tumor does not. One way to minimize the side effects is to lower the radiation dose and increase the number of sessions, sometimes to as many as 35.

"We would like to decrease the margins and increase the radiation dose, in order to control the tumor better without side effects," says Gino Fallone, director of the medical physics division at the University of Alberta department of oncology.

Another challenge is posed by tumor movement during treatment. Tumors in the lungs and the prostate especially may move by about two centimeters during treatment. Current radiotherapy deals with this challenge by combining the radiation source with a computed tomography (CT) scan. This helps doctors reduce damage to healthy tissue, but CT scans are not very good at showing soft tumor tissue, and they are too slow to track tumor movement in real time. Fallone's group has turned to magnetic resonance imaging (MRI), which provides crisp pictures of soft tissues such as tumors, in the hopes of doing better.

Until now, it hasn't been possible to use MRI to guide radiotherapy. This is because MRI machines and the linear accelerators that supply high-energy x-rays for radiotherapy interfere with each other. MRI uses a strong magnet and pulses of radio-frequency waves to excite and read a signal from protons in the water molecules inside soft tissues in the body. Medical linear accelerators also use radio-frequency pulses, in their case in order to accelerate electrons through a waveguide toward a metal target. When the electrons hit the target, high-energy x-rays come out the other side; these x-rays are then aimed at tumor tissue. If these two machines are in the same room, the magnetic field from the MRI interferes with the waveguide, preventing the electrons from being accelerated, and the radio-frequency pulses from the linear accelerator interfere with the imager's magnetic field, degrading picture quality.

To combine the technologies, the Alberta researchers had to reengineer both components. "The whole machine is designed differently," says Fallone. Special shielding is employed. And instead of using a high-strength magnetic field generated by superconducting-wire coils, as in clinical MRI, the machine uses a weak permanent magnet. The weak magnet interferes much less with the accelerator and is smaller and less expensive to operate. This December, Fallone's group published the results of imaging studies that showed it was possible to generate MRI images while running the linear accelerator without interference.

The weak magnet imposes a different challenge, however: the image quality is much lower. So researchers at Stanford University are working on computational methods for getting the necessary information from these lower-resolution images. "Diagnostic MRI requires a very high image quality, but for radiotherapy you don't need to see the tumor in exquisite detail," says Amit Sawant, an instructor in radiation oncology at the Stanford School of Medicine. "You can afford to lose [image] signal, and still get enough information to know when the tumor is moving." What's important to see during radiotherapy, says Fallone, are the edges of the tumor.

Fallone and Sawant will present initial results of image-tracking studies done with the prototype combined device at the conference in Anaheim. Sawant's group will describe imaging software that allows the machine to acquire five two-dimensional MRI images per second--much faster than conventional MRI. The Stanford researchers increased the imaging speed by decreasing the imaging area and using a technique called compressive sensing. When images are stored, about 90 percent of the data is thrown out; using compressive sensing, it's possible to acquire only the most important 10 percent of the image data in the first place.

Fallone will present results demonstrating that such real-time guidance can be used to redirect the prototype device's x-ray beam. "So far, only CT has been available for image guidance," says Bhadrasain Vikram, chief of the clinical radiation oncology branch of the National Cancer Institute's Radiation Research Program. "It's exciting that [MRI] is becoming available to start asking whether it can provide more accurate information." Better guidance for radiotherapy, says Vikram, might speed up the treatments or even "cure some cancers you can't cure today."

But before the system can be tested on patients, the researchers caution that the image-acquisition process needs to be sped up even more, so that it's possible to make 3-D images. The device will also need to be tested on animals. Fallone estimates that human tests are at least five years away.

http://www.technologyreview.com/biomedicine/23078/

Cheaper Solar Thermal Power

A simpler design could reduce the cost of solar power generated by concentrating sunlight on Stirling engines.

By Kevin Bullis

Stirling Energy Systems (SES), based in Phoenix, has decreased the complexity and cost of its technology for converting the heat in sunlight into electricity, allowing for high-volume production. It will begin building very large solar-power plants using its equipment as soon as next year.

Sun catchers: This is the latest design of a system for focusing sunlight on a Stirling engine to generate electricity. Credit: Sandia National Laboratories/Randy Montoya

The company is currently building a 1.5-megawatt, 60-unit demonstration plant that will use the company's latest design. Stirling expects to finish that project by the end of the year. It also has contracts with two California utilities to supply a total of 800 megawatts of solar power in Southern California. The first of the plants that will supply this power could be built starting the middle of next year, pending government permits and loan guarantees from the U.S. Department of Energy (DOE).

The projects are part of a resurgence in what's known as solar thermal power. Various solar thermal technologies were developed starting in the 1970s, but a breakdown in government funding and incentives caused them to stall before they reached a scale of production large enough to drive down costs and allow them to compete with conventional sources of electricity. "It was a classic problem with solar. The market support to bring solar to high volume wasn't there," says Ian Simington, the chairman of SES and chief executive of the solar division of NTR, a company based in Dublin, Ireland, that bought a controlling share of SES last year.

Recent state mandates and incentives for renewable energy have led to a new push to commercialize the technology. There are over six gigawatts of concentrated solar power under contract in the southwestern United States right now, says Thomas Mancini, program manager for concentrated-solar-power technology at Sandia National Laboratory in Albuquerque, NM. That's equivalent to about six nuclear-power plants. BrightSource Energy has contracts to provide 1.3 gigawatts of solar power with concentrated solar power, and Solar Millenium has announced a project that would generate nearly one gigawatt of power.

Stirling Energy Systems technology uses 12-meter-wide mirrors in the shape of a parabolic dish to concentrate sunlight onto a Stirling engine. The difference in temperature between the hot and cool sides of the engine is used to drive pistons and generate 25,000 watts of electricity. The first phase of the company's large-scale projects will use 12,000 of these dishes to generate 300 megawatts of power. Simington expects electricity from the systems to cost between 12 and 15 cents per kilowatt hour, higher than the cheapest sources of electricity--such as coal-fired power plants--but competitive in many markets, especially in the afternoon, when prices are highest.

Earlier this month the company unveiled its production design. Compared to several prototypes that have been tested for several years at Sandia National Laboratory, the new design cuts about two metric tons from the weight of each dish and reduces the number of mirrors in each from 80 to 40. The simplified design can be built in large quantities using equipment in existing factories for automobiles.

The company's design has certain advantages over other approaches to concentrated solar power. In other systems, heat is collected over a large area and used to drive turbines in a central facility. These turbines require large amounts of water for cooling, Mancini says, whereas the SES system uses a closed-radiator system that doesn't consume water. Water use is an important consideration for solar thermal technologies, Mancini adds, since they work best in areas with a lot of direct sunlight--that is, in deserts. (These concentrated-solar-power systems are quite different from solar water heaters used in homes.)

Another advantage of the SES system is its modularity. With other approaches, the entire solar collection and generation system has to be in place to start generating electricity. With the Stirling engine system, power can come online as the dishes are installed, and more generating capacity can easily be added by building more dishes, without any need to enlarge a central generating plant.

But the system also has a significant disadvantage. Other solar thermal power plants collect heat in a central place where it can easily be stored, making it possible to generate electricity when the sun isn't shining. "There's no obvious way to do this with the dishes," Mancini says.

Although there has been a resurgence in contracts for solar thermal power, obstacles to the plants being built still remain. The new projects could be stalled by slow action from the government. Permits originally thought to be ready by the end of this year are now expected no sooner than next May. What's more, the current economy has made financing hard to come by, says Sean Gallagher, SES's vice president for market strategy and regulatory affairs. That has forced his company and others to rely on Department of Energy loan guarantees. But, Gallager says, although the DOE has promised to speed up its process for issuing these, it has yet to issue even the rules for applying for the guarantees included in February's stimulus package.

http://www.technologyreview.com/energy/23079/

Protein Treatment Repairs Heart Damage

The treatment causes adult heart-muscle cells to proliferate and cardiac function to improve.

By Amanda Schaffer

By injecting a protein into mice with heart damage, researchers in Boston have shown that it's possible to cause adult heart-muscle cells to proliferate and cardiac function to improve. The approach could eventually prove valuable for heart-attack patients who have lost cardiac-muscle cells and some cardiac function, especially since existing therapies are unable to regenerate or restore these lost cells.

http://link.brightcove.com/services/player/bcpid263777539?bctid=30331437001

Repair job: The green spots in this video show the division of cardiac-muscle cells as a result of the experimental treatment. Credit: Bernhard Kühn/Cell

Several large research groups are working on techniques to regenerate heart tissue or shore up heart function using stem cells, and some of these projects have reached clinical trials. The Boston team's work, led by Bernhard Kühn at Children's Hospital Boston, instead focuses on stimulating adult heart cells, an alternative approach that could, in theory, lead to less invasive and less expensive treatments.

Kühn's work is "very exciting" in that it involves using "protein therapy to harness cardiac regeneration," says Roger Hajjar, director of the cardiovascular research center at Mount Sinai Medical Center in New York, who was not involved in the research.

For years, the prevailing dogma was that adult cardiac cells do not regenerate. Some researchers have shown, however, that at least some cardiac cells are, in fact, capable of dividing. But following a heart attack, they do not proliferate sufficiently to repair the resulting damage. Kühn's work suggests a novel way in which they could be stimulated to do so.

In a study published today in the journal Cell, Kühn and colleagues first showed that a protein called neuregulin1 can cause fully mature heart-muscle cells from mice to divide and proliferate in a petri dish. The researchers then injected this protein into mice with heart damage. After 12 weeks of daily injections, the animals' hearts showed less hypertrophy, or enlargement, and improved function. For instance, the hearts had about a 10 percent increase in ejection fraction--the fraction of blood pumped out of the left ventricle with each beat. The treatment "didn't make the damage go away completely," says Kühn, "but it did make the heart work significantly better."

Going forward, one potential worry is that Kühn's team injected the protein systemically, meaning that it traveled throughout the animals' bodies. In addition to the heart, cells in the breasts and nervous system also express receptors for the therapeutic protein, which raises the risk of unwanted cell division. "We were nervous about the treated mice developing breast tumors or producing milk," Kühn acknowledges. "We did not see abnormalities when we looked at the breasts macroscopically. But we plan to study breast and nervous tissue," more closely in future research, he says. A therapy that could be injected directly into the blood would be relatively easy and inexpensive to administer, he notes.

However, others say that systemic injections would be too risky in people, especially since cancer cells might already be present in some patients. If this therapy were to move forward, it would be "extremely important to deliver the protein locally," says Hajjar.

A few previous studies have also shown that proteins injected into animal models can cause division of adult heart cells and improvement in cardiac function. In 2007, Kühn found that a different molecule, a protein called periostin, also caused some cardiac-muscle cells to proliferate, improving heart function. In 2006, another group at Children's Hospital Boston used a regimen with a protein called fibroblast growth factor and found that it too resulted in heart-cell proliferation, reduced scarring, and improved function.

Most animal and human studies have focused, however, on various kinds of stem cells. Many researchers believe that the adult heart contains a small number of tissue-specific stem cells, which could potentially play a role in regeneration and repair. Piero Anversa of Brigham and Women's Hospital in Boston recently began phase-one trials for an approach in which cardiac stem cells are isolated from patients, expanded in the lab, and then reinjected. Anversa has shown that a cocktail of growth factors, injected into dogs, causes native cardiac stem cells to differentiate into mature cells and improve heart function. Meanwhile, Eduardo Marban, director of the Cedars-Sinai Heart Institute in California, has pioneered a related technique. His team removes small pieces of tissue from patients' hearts, grows a collection of cells, including cardiac stem cells, and then injects the cells into patients' coronary arteries.This work is also in phase-one trials.

Other researchers are focusing on stem cells derived from bone marrow. And in other research conducted in pigs and, preliminarily, in humans, the use of bone-marrow cell therapy has improved heart function.

One advantage of cell therapy is that the cells could be administered less often, in theory, than a drug or protein therapy, says Joshua Hare, director of the Interdisciplinary Stem Cell Institute at the University of Miami, although the administrations would also likely be more invasive. Several cell-therapy approaches are also further along in the research process and could potentially be available to patients sooner.

Still, there may be some overlap in how protein therapy and cell therapy could work in the heart. Some of the benefits of cell therapy may come from stimulating endogenous pathways similar to or the same as the one targeted by Kühn, says Hare. It's possible that part of the underlying biology is similar, he adds, and "we just have to figure out the best way to manipulate it."

http://www.technologyreview.com/biomedicine/23060/

A Contest to Train Cyber Combatants

Cyber-defense and capture-the-flag contests will help train future defenders of cyberspace.

By Robert Lemos

In the 1950s, shocked by the Russians' launch of Sputnik, the United States embarked on an initiative to boost its numbers of scientists and engineers. Now, private industry, academics, and government agencies are banding together to create a similar push to educate and train at least 10,000 students to become the future defenders of cyberspace.

Credit: Technology Review

On Monday, the Center for Strategic and International Studies, the SANS Institute, the U.S. Department of Defense (DoD), and several university and private-industry partners plan to announce the U.S. Cyber Challenge, a triathlon of competitions designed to inspire students to learn the technical skills needed to defend--and, in some cases, attack--computer networks.

Alan Paller, director of research for the SANS Institute, an organization that educates and trains system administrators and computer engineers, says that schools aren't turning out enough students with the technical know-how to defend critical networks. "This shortage is as tough as the shortage of scientific people we had in the 1950s," Paller says. "The country has about 1,000 people that could compete in a cyber competition at a high level today. We actually need between 20,000 and 30,000."

The consortium behind the U.S. Cyber Challenge hopes that the competitions will boost interest in practical network-administration and computer-security skills. The aim is "training and developing that workforce and getting people excited about digital forensics and training them to work for us," says Jim Christy, director of future exploration for the U.S. Department of Defense's Cyber Crime Center (DC3).

The U.S. Cyber Challenge brings together three competitions under a single umbrella. First is the DC3's Digital Forensics Competition, which pits teams against one another to solve a number of puzzles that an expert might come across when investigating a crime. For example, entrants have to analyze file signatures, check out suspicious software, decrypt files without the password, and parse header files for interesting information. The competition has already proven extremely popular: Nearly 600 teams have registered so far this year, compared to 199 teams last year. The DoD is also considering offering a massive cash prize, up to $1 million, to increase interest in solving the top level of problems: challenges with no known current solution, such as getting data off a severely damaged hard drive.

The second contest is a capture-the-flag competition run by the SANS Institute and designed for college students and high-achieving high-school students. Known as NetWars, the competition is played on a virtual private network over the Internet, using a custom operating-system image created by a small group that runs the game. Teams get points for attacking other teams' virtual machines and controlling certain services and files--the "flags."

"It's mostly attack to start out with," says Ed Skoudis, cofounder of security firm InGuardians and an advisor to the SANS Institute for the game. The result is a fair simulation of attack and defense in cyberspace, Skoudis asserts. Participants try to exploit weaknesses in their rivals' systems and then defend the systems they compromised from the other attackers.

A third competition aims to develop high-school students' knowledge of network defense. The CyberPatriot High School Cyber Defense Competition, which is in its second year, teaches students the difficulty of protecting computer networks against attacks. In the first contest, eight teams competed against each other. This year, 266 schools have signed up, says Gregory White, an associate professor with the University of Texas at San Antonio and the director of the university's Center for Infrastructure Assurance and Security, which runs the program along with the Air Force Association.

Earlier this week, the Partnership for Public Service and consultants at Booz Allen Hamilton released a report concluding that the lack of cybersecurity skills in the federal workforce leaves the "potential for major vulnerabilities for our national security." The Obama administration, too, in its recently released Cyberspace Policy Review, flagged the shortage of well-educated cybersecurity professionals as a problem of national importance.

Aside from potentially funding the forensics challenge, the federal government has not announced funding for the U.S. Cyber Challenge. However, companies such as Google and state governments such as Delaware's have already expressed interest in taking part."If you wait for a committee to do something, you will be waiting for a long time," White says. "[Government officials] seem to be interested, but that has not translated to funding."

http://www.technologyreview.com/web/23066/

A Cell-Phone Microscope for Disease Detection

A cheap smart-phone microscope could bring fluorescent medical imaging to areas with limited access to health care.

By Anne-Marie Corley

In a twist on traditional smart-phone accessories, researchers have demonstrated fluorescent microscopy using a physical attachment to an ordinary cell phone. The researchers behind the device say that it could identify and track diseases like tuberculosis (TB) and malaria in developing countries with limited access to health care, or in rural areas of the U.S.

Snap diagnosis: The Cellscope uses a blue-light LED and filters for fluorescence imaging. The sample is inserted next to the metal focusing knob. Credit: David Breslauer

The "Cellscope," which came out of an optics-class project at the University of California, Berkeley, could capture and perform simple analysis of magnified images of blood and sputum samples, or transmit the images over the cell-phone network for analysis elsewhere.

The contraption--a tube-like extension hooked onto the cell phone with a modified belt clip--works just like a traditional microscope, using a series of lenses that magnify blood or spit samples on a microscope slide. To detect TB, for example, a spit sample is infused with an inexpensive dye called auramine. An "excitation" wavelength is emitted by the light source--a blue light-emitting diode (LED) on the opposite end of the device from the cell phone--and absorbed by the auramine dye in the spit sample, which fluoresces green to illuminate TB bacteria. Then automated software can count the green bacteria for a diagnosis in real time, or the image can be transmitted via cell network to a separate facility where doctors can analyze it and respond.

"The cell phone approach is very valuable for all parts of the world where [medical] resources are scarce," says Aydogan Ozcan, an assistant professor of electrical engineering at UCLA, who is working to develop a lens-free method for mobile cell imaging. "It's a great step forward in this important area."

The researchers involved with the project, led by Berkeley bioengineering professor Daniel Fletcher, describe their work in a paper published in the journal PLoS One. They previously demonstrated a prototype device that used white light, or bright-field imaging, to capture magnified images of blood cells stained to detect malaria parasites, an approach that could also identify the oddly shaped red blood cells indicating sickle cell disease. Fluorescence adds a new capability that could be particularly useful if made cheaper and portable.

"Fluorescence microscopy in resource-poor countries is hard," says Wilbur Lam, a bioengineer and physician in the UCSF School of Medicine who worked on the project as a clinical expert. "Lab-grade [fluorescence] technology is expensive and hard to operate," he says. "You need a dark room, a mercury lamp, and a lot of training." These facilities aren't available in many areas of developing nations, which, Lam notes, are the places that most need the technology to detect common diseases like TB. The Cellscope device could be distributed to health workers in remote areas, extending the reach of fluorescence-based medical imaging.

According to Fletcher, fluorescence is increasingly preferred by the World Health Organization as a TB detection tool, because it's easier for the untrained eye to spot something green than to pick out a colored stain against a bright-field background. However, with traditional fluorescence equipment, health workers still have to count spots on a microscope slide by eye, which can be unreliable. The Berkeley group developed software that counts the green spots automatically; when installed on the smart phone, it could make the process easier and faster.

The cell-phone microscope could also be useful for TB therapy, Lam says. TB patients must be directly observed taking their medication over several weeks, to prevent drug resistance buildup. The phone can store images for comparison, and it provides immediate feedback, so patients could go to their local health worker and see their progress each week, rather than waiting a month for samples to come back from a centralized processing location, or seeing complications of the disease show up three or four months later.

That ability to transmit microscope images makes the Cellscope a new tool for telemedicine, says Lam. And because the images can have GPS tags associated with them, they could provide early warning for disease outbreaks.

Digitizing medical records is another problem for health workers in the field. Fletcher's group ran into the issue while demonstrating their technology in Bangladesh and the Democratic Republic of Congo. Pen-and-paper records are easily lost--a problem that the cell-phone microscope could solve by attaching patient-identification information to each digital image. Records could then be called up for easy reference when a patient returns to the health clinic.

The researchers' key innovation, Lam says, was not inventing a new medical test, but rather taking a standard test and presenting it in a new way. Their technology "just happens to be smaller, cheaper, and attached to a cell phone," he says.

In a world with four billion cell phones, many in developing countries, Ozcan says, the cell-phone microscope could take advantage of existing infrastructure to fight disease on a new, more mobile front.

http://www.technologyreview.com/biomedicine/23059/

The Business of Personal Genomes

Jorge Conde speaks on the complexities of personal genomics.

By Emily Singer

In some ways, Jorge Conde, cofounder of the genomics startup Knome, knows his clients more intimately than any other company president. Knome is the first company to sequence and analyze a consumer's complete genome. And Conde and his team have spent a full day with each member of their select clientele, going through the minute details of the results in search of hidden genomic time bombs, subtle health risks, and other information.

Genomic profile: Shown here is a close-up look at a genetic sequence done by Knome, a personal genomics startup in Cambridge, MA. The image shows a chromosome (top) and the letter-by-letter sequence (bottom) in a small section of that chromosome. The pink box highlights a specific genetic variation. Credit: Knome

At $100,000, Knome's product is still out of reach for most consumers. But that could change fast. The cost of genome sequencing is dropping by an order of magnitude every one to two years, and the cost of Knome's product will drop with it, though not quite as fast. (When the company debuted its service in late 2007, it cost $350,000.) That means that within the next few years, having your genome sequenced will cost about the same as cataract surgery, making it affordable to include your genome sequence as an integral part of your medical record.

When launching Knome in 2007, Conde wandered into largely uncharted territory--only a handful of complete human genomes had been sequenced at the time. That meant that the company had to figure out how to select and analyze the most relevant information in the genome and then deliver that information to clients in a useful and digestible way. "We have to make sure they are not overwhelmed and don't misunderstand the information," says Conde. "This hadn't been done before, so we wanted to be responsible, informative, and entertaining."

So far, scientists understand only a tiny fraction of the 3 billion letters of the human genome. Knome's team developed software that combs both public and private genome databases for the latest in scientific research and then applies the findings to an individual's genome. The company has also developed new ways to filter and sort that information, developing a genome browser that allows users to search their genome by disease or by chromosome, and presents disease risk based on the level of confidence that can be gleaned from the existing research on the topic. The strength of the link between a genetic variation and a disease varies widely. Some genetic variants are definitively linked to specific diseases, such as cystic fibrosis or Huntington's disease, others are associated with a high risk of a disease, such as the BRCA mutations and breast cancer, while still others have been linked to a negligible increased risk for common diseases, including heart disease and diabetes.

Conde won't disclose how many people the company has sequenced so far--only that Knome's goal for 2008 was to sequence 20 people. "In comparison to the genomes that have been published, we think we've done more than anyone," says Conde. Some clients buy their genome sequence to help plan how to maintain their health. "Others do it for the shear thrill of having a front-row seat of what's going on in science," says Conde.

Customers so far have been mostly men--about 80 percent--and mostly in their mid-50s. A significant fraction of Knome's clients are from outside the United States, thanks to word-of-mouth recommendations from early customers. Dan Stoicescu, a millionaire living in Switzerland who was profiled last year in the New York Times, was the company's second client. Knome recently signed up two new customers, Harvard professor Henry Louis Gates Jr. and his father, Henry Louis Gates Sr., as part of a new documentary series slated to run on PBS next year.

People interested in having their genomes sequenced first go through an initial consultation "to make sure they understand what we can and cannot do," says Conde. "When you're operating at this price point, you don't want an unsatisfied customer." One of the biggest controversies in personal genomics to date has been the utility of currently available genetic information, especially for variations that have been only weakly linked to disease. For this reason, consumer genomics companies, including Knome, specify that they are not providing a medical service.

DNA is then isolated from a client's blood sample and sent to the Beijing Genomics Institute in China to be sequenced. Once complete, the sequence is analyzed at Knome. In order to assuage privacy concerns, the sequence data, along with the genome browser, reside only on a USB key given to the individual. "With this approach, you are the gatekeeper of your information," says Conde.

Clients get their key at an in-person meeting devoted to their genomes, where they are schooled by a clinical geneticist, a genetic counselor, a bioinformatician and others. (Clients are invited to bring their personal physicians, says Conde, though most don't.) "We spend the entire day going through genetics and sequencing 101, and then walking them through their genome," says Conde. "People often start out tense, thinking there will be a ticking time bomb in their genome. But then they start to relax and ask questions."

Knome hasn't yet found any ticking time bombs, such as the genetic variant that causes Huntington's disease. But Conde says that a couple of people were found to be carriers of genetic variants linked to rare diseases--meaning they will not develop the condition themselves, but might pass it to their children if their mate is also a carrier. And the company has found some rare variants that are highly associated with a particular condition. "One person has a high risk for developing age-related macular degeneration," says Conde. That gives him the option of doing early screening for the disease, though few preventative treatments are currently available.

Part of the service is figuring out what consumers understand, an issue that geneticists and ethicists have been grappling with as genomic information becomes more complex. "You don't realize which concepts will connect, which are understood and misunderstood," he says, adding that clients to date have run the gamut from very knowledgeable to minimally informed about genetics. He says it has been difficult for people to grasp the difference between genetic variations that cause disease, such as the Huntington's mutation, and those that are merely associated with different diseases--meaning that research studies have found a link between these genetic sequences and a disease, but it's not clear what role the gene plays or how strongly it increases disease risk in an individual. The latter represent the majority of disease-linked mutations identified to date.

Conde says that the lessons learned from the early adopters will serve the company well as more people can afford to invest in genome analysis. The company is currently developing a new, more-automated genome-interpretation service that will be offered in conjunction with genome sequencing from Illumina, a genomics technology company headquartered in San Diego. Illumina announced last month that it would offer personal genome sequencing for $48,000, but with minimal analysis of the data included. Analysis of the meaning of the human genome is proving to be more much more complicated than the sequencing itself. "In the long-term, that will be a big driver of value," says Conde. "We will see the high price point go away, and the real value for both individuals and companies will be to provide an ongoing narrative."

http://www.technologyreview.com/biomedicine/23058/

Making Light Bulbs from DNA

Dye-doped DNA nanofibers can be tuned to emit different colors of light.

By Prachi Patel

By adding fluorescent dyes to DNA and then spinning the DNA strands into nanofibers, researchers at the University of Connecticut have made a new material that emits bright white light. The material absorbs energy from ultraviolet light and gives off different colors of light--from blue to orange to white--depending on the proportions of dye it contains.

DNA light: Coating an ultraviolet LED with DNA nanofibers containing dyes creates a bulb that emits bright white light. Credit: Angewandte Chemie

The researchers, led by chemistry professor Gregory Sotzing, create white-light-emitting devices by coating ultraviolet (UV) light-emitting diodes (LEDs) with the material. They are even able to fine-tune the white color tone to make it warm or cold, as they report in a paper published online in the journal Angewandte Chemie.

The new material could be used to make a novel type of organic light bulb. The light emitters should also be longer-lasting because DNA is a very strong polymer, Sotzing says. "It's well beyond other polymers [in strength]," he notes, adding that it lasts 50 times longer than acrylic.

The color-tunable DNA material relies on an energy-transfer mechanism between two different fluorescent dyes. The key is to keep the dye molecules separated at a distance of 2 to 10 nanometers from each other. When UV light is shined on the material, one dye absorbs the energy and produces blue light. If the other dye molecule is at the right distance, it will absorb part of that blue-light energy and emit orange light.

By changing the ratio of the two dyes, the researchers can alter the combined color of light that the material gives off. Varying the amount of dye also lets them make finer tweaks. For example, by increasing the proportion of dye in the DNA from 1.33 percent to 10 percent, they can change the white light from cool to warm. "As you go across the white spectrum, if you want a soft yellow-type light or blue-type light, you can get these very easily with the DNA system," Sotzing says.

Others have used nanostructured materials such as silica nanoparticles and block copolymers--self-assembled materials containing two linked polymer chains--to get the right spacing between the two dyes. But, says David Walt, a chemistry professor at Tufts University, "the advantage in the present system seems to be that the DNA fibers orient the dyes in an optimum way for efficient [fluorescence energy transfer] to occur." Furthermore, when larger amounts of dye are used in the other materials, they start to aggregate. This has two effects: it decreases energy transfer between them, dimming the light output, and it also prevents precise color tuning.

To make the fibers, Sotzing and his colleagues make a solution of salmon DNA and mix in the two types of dye. The solution is pumped slowly out from a fine needle, and a voltage is applied between the needle tip and a grounded copper plate covered with a glass slide. As the liquid jet comes out, it dries and forms long nanofibers that are deposited on the glass slide as a mat. The researchers then spin this nanofiber mat directly on the surface of an ultraviolet LED to make a white-light emitter.

During the fiber-spinning process, the two different dye molecules automatically attach themselves to two different locations on the DNA. The researchers have found in previous work that the nanofiber mats produce 10 times brighter light than thin films of the dye-containing DNA.

"It's really very cool [work], and I think that it has practical promise," says Aaron Clapp, a professor of chemical and biological engineering at Iowa State University. "[But] it seems like an overly dramatic way of doing it."

Clapp speculates that instead of relying on energy transfer between the two fluorescent dyes, you could just change their ratios and get the colors you want.

However, each dye would then require a different input energy source as opposed to just one UV source, Sotzing points out. What's more, energy transfer between two dyes gives better control over the color of the output light.

Walt says that it may be possible to use the first dye to transfer energy to multiple dyes and get an even wider range of colors. "The results reported here suggest DNA-[energy transfer] light emitters are promising," Walt says, "but the ultimate utility will depend on factors such as lifetime and power efficiency."

http://www.technologyreview.com/energy/23042/