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MEETING NEWS Natasha Smith reports from the NIST–NCI Workshop and Technologies—Gaithersburg, Md.
on Standards, Methods, Assays, Reagents,
NIST and early detection of cancer The National Institute of Standards and Technology (NIST) joined forces with the National Cancer Institute’s (NCI’s) Early Detection Research Network to open discussions about developing standards and new technologies to detect cancer in its earlier stages. The workshop that they cohosted in late August focused on biomarker discovery, validation, and applications, with an emphasis on proteomics and MS approaches. The ideal biomarker would clearly distinguish between normal and diseased states and would have a high sensitivity and specificity. NIST team members solicited ideas on the contributions that they could make in developing protein, peptide, and digestion standards and reference materials. Many of the speakers described the challenges presented by MS, including incomplete sampling, quantitation, and discrepancies with search algorithms. Speakers also addressed the calibration techniques that are needed and the quality-control issues that arise when MS instrumentation is used and when researchers try to identify patterns in proteomics data. Particular attention was paid to MS because it is such a widespread technique in proteomics research. Emanuel Petricoin of George Mason University described immuno-MS as one approach for profiling cancer biomarkers. A biomarker is a protein signature that, in the ideal case, can be traced back to the abnormal tissue of origin. Some potential biomarker proteins may not stay intact but rather undergo modification or proteolysis to produce smaller fragments that more readily enter the bloodstream. Some researchers argue that high-molecular-weight proteins in serum, such as albumin, act as carrier proteins; as they circulate in the blood, they bind lower-molecular-weight proteins and peptides. This idea is still new and controversial, but Petricoin and
other researchers suggest that these complexes could be important for biomarker discovery. The small molecules tend to be short-lived, but if they did stick to or form complexes with larger proteins, they might persist much longer; this longevity would make them easier to identify. Sample preparation procedures for serum usually include a depletion step to get rid of the high-abundance proteins and molecules that dominate the sample; the intent is to simplify the search for smaller, less abundant proteins. But if large proteins, such as albumin, are actually partnered with proteins that are carrying diagnostic messages, then valuable information is being thrown away. One alternative is to use protein-specific antibodies to affinity-capture these carrier proteins, says Petricoin. The proteins are concentrated, desalted, and eluted onto a MALDI target; then they are analyzed by MS. Petricoin says that immuno-MS can be used for biomarker profiling if the right tools and equipment are devel-
oped. “Immuno-MS could be the best approach, [because] many of these [putative] biomarkers are fragments of larger proteins and cannot be distinguished from them by normal immunological approaches,” he explains. He sees two possible roles for NIST. First, because low-mass molecules will ultimately be targeted, researchers need suitable calibrants in the low-molecular-mass range. Such standards will ensure precision and accuracy. Second, reference materials are needed to test the performance of immunocapture methods. Petricoin proposes that NIST create a recombinant protein in addition to the antibody against it to qualify the instruments and methods. One of the main challenges, he notes, would be developing wellqualified and specific antibodies that perform well in immunoprecipitation. NIST’s involvement in immuno-MS might help determine whether large proteins can act as carriers for small biomarkers and under which circumstances, if any, biomarkers discovered in this way can be used for cancer diagnostics.
Nanotechnology safety database The Center for Biological and Environmental Nanotechnology at Rice University and the International Council on Nanotechnology have developed a free database of information pertaining to the environmental and health safety risks of nanotechnology. The database is available at http://icon.rice.edu/research.cfm. Nanotechnology research is currently published in a wide variety of journals, including those in the fields of biomedicine, toxicology, and environmental and physical sciences. The archive compiles relevant articles in one place and helps scientists plan new avenues of inquiry, say the developers. With the new database, scientists can search peer-reviewed scientific papers for safety information according to particle type and production method in addition to author, year, and keywords. In the future, the developers plan to add new search functions and establish a separate database containing policy reports and commentaries.
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GOVERNMENT AND SOCIETY FBI bullet-lead tests terminated Concerns about the validity of bullet-lead examinations prompted the Federal Bureau of Investigation (FBI) to call a halt to the tests in September 2005. Although the agency contends that the technology was sound, it says that the tests will no longer be conducted because of concern about how to interpret the results. Bullet-lead examinations involve an analysis of elements found in bullets, including tin, copper, and silver, to match bullets found at a crime scene with those found in a suspect’s possession. The agency had declared a moratorium on bullet-lead examinations in February 2004 because of a National Research Council (NRC) report, which came to the same conclusions as the FBI just has.
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According to the NRC report, bullets can reliably be chemically matched to each other. The problem is whether two bullets that are chemically indistinguishable from one another necessarily came from the same weapon or round of ammunition. “Every step from smelting the lead to buying the ammunition in a store provides opportunities for bullets with different compositions to be mixed and for bullets with the same compositions to be shipped separately to different outlets in a region or to different regions,” says the report. The report also notes that the number of bullets that are chemically indistinguishable is 12,000 to 35 million. FBI Laboratory director Dwight Adams says, “Bullet manufacturing in-
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formation is either proprietary or unavailable, so we have no way to measure the significance of two bullets matching each other.” Adams says that bullet-lead examinations were done only rarely, usually when investigators could not compare bullets to gun-barrel striations—for example, in cases where no gun was found. The FBI estimates that the tests have been used in ~2500 cases since the early 1980s. This could change Michael Behn’s life. He was charged with murder and robbery in 1995. Bullet-lead evidence was presented during his trial, but last March, an appellate judge ordered a new trial, which is currently pending. a —Betsy Querna
