Frontlines

Efforts to keep Russian scientists fully employed, thus away from countries seeking their expertise in making weapons of mass destruction, seem to be bearing fruit, according to Victor Alessi, president and CEO of the Arlington, Va.-based US Industry Coalition (USIC). Of 120 scientific projects in development, 27 are biology related. One such effort is the development of a high-speed needleless injector. The US Food and Drug Administration has approved the Russian design, and the injector should reach the market in a year or two, Alessi told participants at the 2002 Annual Meeting of the American Association for the Advancement of Science in Boston. The project results from collaboration among the US Department of Energy's Kansas City, Mo., plant, which makes nuclear weapons components; Felton International, of Lenaxa, Kan., and Russia's Chemical Automatics Design Bureau. "The components themselves will be manufactured in Russia and shipped to the United States for final assembly," says Gary Tydings, USIC chief operating officer. The injector can vaccinate 600 people an hour. And, it is only one of many projects employing scientists. "We are now on the point of having hundreds of people with permanent jobs and on the brink of thousands," Alessi says. "The injector project is one of 120 projects supported by the DOE Initiatives for Proliferation Prevention program, which has budgeted $30 million US this year, with 60% going to pay Russian scientists' salaries, and the remainder going to the federal labs that validate the Russian efforts." Private businesses, such as Felton International, provide at least a 100% match in dollars and/or services, as well as raising money from investors for commercialization.

To aid scientists in navigating boundless life sciences data sources, the European Commission (EC) will provide ¤5 million over the next three years to the European Molecular Biology Organization (EMBO) to coordinate E-BioSci. The project involves a corporation and seven institutions from France, Germany, Spain, and the United Kingdom, that have expertise in opening access to and allowing retrieval of digital information. Les Grivell, project manager of E-BioSci, says the group must still develop Web tools and navigational expertise and create a platform for providing rapid access to the data. The Online Research Information Environment for the Life Sciences Consortium (ORIEL) will oversee the construction of the Web infrastructure. "The EC wants to develop the technology to bring all this in-depth, technical information together—full-text, sequences, and multidimensional image databases—and establish the tools and navigation to make sense of it all," says Amanda Proctor of Ingenta, a Bath, UK, Web-service company, and one of the project's seven partners. If the technology is successfully used in the data-rich life sciences, Proctor predicts, the tools may be replicated for use in other fields. David Shotton, project director for the bioimage data project of ORIEL, says the data project will allow scientists to fill databases with experiment results that would otherwise never see the light of day. "By the end of the project, we also will have aligned E-BioSci with emerging standards and be most of the way in broadening towards other types of sciences."

How about Barry Commoner's piece in Harper's? In taking a major swipe at DNA, the Human Genome Project, and agricultural biotech, (B. Commoner, "Unraveling the DNA Myth," Harper's Magazine, 304:39-47, February 2002), the crusading environmentalist drew about 250 E-mail requests to his office at Queens College, City University of New York, for the accompanying references. He's analyzing the many comments, but he says that about half were from academicians and most were favorable, alongside "a few nasty ones, of course." Dissenters took issue with his premise that the Human Genome Project refuted its own scientific rationale in demonstrating that the so-called central dogma of a one-to-one relationship between genes and their encoded proteins is way off. People wrote that this news is old hat, a point Commoner made in his article. "My complaint is that nobody ever said it," he adds. An implication of phenomena such as alternative splicing that give rise to variations in genetic information is that a transgene's effects on its host organism are neither predictable nor safe, he argues. Commoner and molecular geneticist Andreas Athanasiou of Canada's York University are now systematically combing the Human Genome Project's mass of data to critically examine "discordant evidence." Stay tuned.

Beta cells, once called the innocent bystanders of the autoimmune response that results in their destruction and invariably diabetes, may play a more active role in their own defense. Type I diabetes has often been associated with multiple viral infections—particularly infections from Coxsackie virus B4, which has an affinity for exocrine cells. Researchers at the Scripps Research Institute in California found that a strong b cell response to interferons in the presence of CVB4 protects them from destruction by further immune system activity. Interferons trigger a cytokine signaling cascade in cells that invariably gums up viral replication. "Beta cells are really exquisitely differentiated to regulate viral load," says Nora Sarvetnick, professor of immunology at Scripps. The group created transgenic mice that express the suppressor of cytokine signaling 1 (SOCS-1) under the control of an insulin promoter effectively disabling the IFN-mediated response in b cells. In the absence of this first line of defense, infected cells are targeted by the innate immune response. "Beta cells that can't regulate viral load are destroyed by natural killer cells. I believe this kind of mechanism is really what initiates diabetes in humans," Sarvetnick explains. She says genetic differences in the signal transduction pathway may affect some people's abilities to clear viruses through IFN-mediated response, which could result in rapid onset of diabetes following viral infectins.

Cardiac arrest, seizures, extreme irritability, and impotence are all attributed to cocaine use. Researchers at the University of California, Los Angeles, AIDS Institute have added another deleterious side effect: the accelerated spread of HIV. These scientists, using an animal model, have demonstrated for the first time that cocaine accelerates HIV replication in human peripheral blood leukocyte (PBL) (M.D. Roth et al., "Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes," Journal of Infectious Diseases, 185:701-5, Feb. 15, 2002). Researchers injected PBLs into immune-incompetent, HIV-infected mice in the presence and absence of cocaine. A nine-fold drop in CDT-4 cells and a 200-fold increase in the blood's AIDS viral load were found in the mice exposed to cocaine. Prior epidemiological studies had shown a correlation between cocaine use and HIV replication, but Gayle Baldwin, assistant professor of medicine at UCLA, says these results were much more dramatic than anticipated. The exact mechanism responsible for this link isn't clearly delineated and is the next step in the investigation, Baldwin says. "The effect of cocaine on HIV co-receptors, the cytokine milieu, and the byproducts from its metabolism are a few places we already know to look."

A team of researchers has taken a nanoscale step toward creating a simple handheld genetic-testing device that could eventually find its way into every doctor's office (S.-J. Park et al., "Array-based electrical detection of DNA with nanoparticle probes," Science, 295:1503-6, Feb. 22, 2002). The scientists, led by Chad Mirkin, chemistry professor and director, at Northwestern University's Institute for Nanotechnology, placed pairs of electrodes separated by a 20-µm gap on silicon wafers, with oligonucleotides in the inter-electrode space. Then they incubated the chip with both target DNA and 13-nm gold nanoparticles conjugated to another oligo. As gold particles fill the inter-electrode gap, they create a bridge that closes the circuit, changing an insulator into a conductor. The researchers used photographic development solution—silver and hydroquinone—to increase each particle's diameter, and hence, the assay's sensitivity. "The beautiful thing is, it's simple enough to be engineered [to make] a handheld device that could conceivably be used by a doctor ... over the course of an office visit," says Mirkin, whose company, Northbrook, Ill.-based Nanosphere Inc., is working to commercialize this technology. But don't count out traditional biochips just yet, says Affymetrix Fellow Richard Rava: "Generally, electrical methods suffer from high backgrounds in complex biological specimens (the paper uses pure oligos) which limit the general utility of such techniques." John Ambroziak, director, genomic services and discovery, at MWG-Biotech Inc. of High Point, NC, adds that electronic biochips are also more complicated and expensive to produce than are standard arrays.