NEWS OF THE W EEK
© 2008 SC IE NC E
INSIDE VIEW X-RAY MICROSCOPY: Technique
provides high-resolution images of object interiors
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NEW HIGH-RESOLUTION imaging technique
bridges the gap between two different types of microscopy. The technique allows scientists to view a wide variety of electronic and biological samples at higher resolution and to visualize specimen interiors, which wasn’t possible with the earlier methods. The new technique, scanning X-ray diffraction microscopy (SXDM), combines the high resolution of coherent diffractive imaging (CDI) and the ease of sample preparation of scanning transmission X-ray microscopy (STXM). According to its developers, SXDM makes possible “imaging of the finest structures in state-ofthe-art electronics devices or the macromolecular assemblies in organic tissues” (Science 2008, 321, 379). CDI creates images by extrapolating structural information from the diffraction patterns of X-ray beams as they strike the specimen. This technique can produce high-resolution images, but image reconstruction and specimen preparation can be very difficult, and the range of accessible samples is limited
INNER BEAUTY
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SXDM combines diffraction patterns, such as those shown for a buried nanostructure test sample, to obtain high-resolution images of objects’ interiors, something not previously possible.
ROCHE SUSPENDS HIV DRUG RESEARCH PHARMACEUTICALS: Finding
nothing new to offer against HIV, firm calls it quits
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The search for new drugs involves multidisciplinary approaches. Here, a Roche scientist inspects protein crystals for potential drug candidates.
WISS PHARMACEUTICAL COMPANY Roche has discontinued research on HIV therapies after determining that nothing in its pipeline would offer enough benefit over existing drugs to warrant further development. Roche had been investigating several new antiretrovirals, all of which were at the preclinical stage and at least six years away from the market. Roche will, however, continue to support the few therapies and diagnostics it already makes, according to a company spokeswoman. These include the protease inhibitors Invirase and Viracept (sold outside the U.S.) and the cell-fusion inhibitor Fuzeon. In 2007, worldwide sales of Fuzeon reached $267 million but dropped 34% in the first quarter of 2008 because of competition from new HIV drugs. In 2006, Roche stopped selling Hivid, which was launched in 1992 and was one of the first three HIV drugs marketed, as other treatments superseded it. About 30 individual medicines or combinations are WWW.C E N- ONLI NE .ORG
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to specimens completely isolated on a clean surface. STXM forms images by measuring the transmitted intensity of an X-ray beam as it scans a sample. Although STXM allows the use of a much wider variety of specimens, its image resolution is limited by the size of the X-ray beam’s focal spot. Now, postdoc Pierre Thibault, assistant professor Franz Pfeiffer, and coworkers in the physics department at the Paul Scherrer Institut, in Villigen, Switzerland, have developed SXDM, an imaging and data reconstruction technique, to address the specimen applicability and resolution restrictions of the earlier techniques. In their SXDM study, the researchers used a scanning beam of high-energy X-rays (as in STXM) and a high-speed detector to analyze a specimen containing a buried nanostructure. The team then examined the resulting X-ray diffraction patterns by the CDI method and reconstructed the image over a wide area of the sample. High-energy “X-rays can penetrate several tens of microns of material and can therefore image, in a noninvasive way, a buried nanostructure otherwise impossible to see,” Thibault says. These results, says physicist Chris Jacobsen of Stony Brook University, in New York, “show an impressive advance in spatial resolution and ease of reconstruction.” Proposed uses for SXDM include investigating the interiors of superconductors and subcellular structures.—CARRIE ARNOLD
available to treat the 33 million people infected with HIV. Another 50 drugs are in clinical development, according to the industry trade group Pharmaceutical Research & Manufacturers of America. Market research from Datamonitor predicts the global HIV drug market will grow about 3.7% per year to $11.5 billion in 2016. Roche will redeploy scientists in HIV research to other activities, its spokeswoman says. The company’s virology efforts are largely focused on hepatitis C, with three products in clinical trials. If Roche identifies a significant HIV-related breakthrough outside the company, she says it would consider contributing in some way, as it did in developing Fuzeon with the biotech firm Trimeris. In the past, activists have targeted Roche for its drug-pricing policies in poor countries and the $25,000 annual cost for Fuzeon. The difficult-to-manufacture peptide drug was the first new treatment for drug-resistant patients, points out Jules Levin, executive director of the National AIDS Treatment Advocacy Project. AIDS advocacy groups regret the loss of any research efforts. Although a burst of new drugs has hit the market in the past two years, the pipeline is actually pretty skimpy, says Peter Staley, founder of informational website AIDSmeds.com. Most candidates are only in early clinical trials. Roche’s commitment to hepatitis C, however, is viewed as important because the disease is a leading cause of death for those people also infected with HIV.—ANN THAYER
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