Notebook

NEW AND IMPROVED: Hoechst Merion Roussel's new research facility (inset) in Bridgewater, N.J. will house activities in biotechnology, automated screening and robotics, computational and medicinal chemistry, molecular modeling, and biophysics. Automated high throughput screening (above) will allow researchers to search huge chemical libraries for promising therapeutic compounds. OPENING DAY AT HOECHST Hoechst Marion Roussel (HMR) Inc., based in Frankfurt, Germany, marked the beginning of a new age of scientific discovery with the opening of its $43 million research facility in Bridgewater, N.J. The three-story laboratory building will accommodate 200 researchers in analytical and medicinal chemistry, automated chemical synthesis, molecular modeling, and genomics. At a dedication ceremony on April 28, Richard J. Markham, CEO of HMR, said the building doubles the research capabilities at the Bridgewater campus, representing HMR's continuing commitment to the state of New Jersey and to innovation in drug development. "Obviously our presence here provides us significant access to a highly skilled and extremely talented workforce," Markham remarked. "In addition, it offers proximity to the Food and Drug Administration, leading academic centers, and the headquarters of key competitors." The region has earned a reputation as a major center for pharmaceutical research and manufacturing in the United States. More than 50,000 people in New Jersey are employed in the industry. Merck and Co., based in Whitehouse Station, N.J. is just miles away, and Pharmacia and Upjohn Inc. will soon move into a facility only blocks away. HMR's new research building features open floor plans as well as the latest in bioinformatics and automated screening. Research functions housed here will initially support the Bridgewater-based central nervous system, oncology, and respiratory disease groups. COMMON COLD: A view of the common cold virus, which has 60 sites capable of connecting to ICAM-1 receptors, is depicted in the computer-simulated model. ICAM, THEY SAW Knowing your way around the battlefield is a necessary first step on the road to victory. Just ask researchers at Purdue University. A team of investigators led by Michael G. Rossmann, a professor of biological sciences at Purdue, have successfully mapped in atomic detail the three-dimensional structure of the intercellular adhesion molecule-1 (ICAM-1), a receptor cell that binds to rhinovirus, the most common cause of the common cold (J. Bella et al., Proceedings of the National Academy of Sciences, 95:4140-45, 1998). Through an understanding of the structure of ICAM-1, scientists hope to discover precisely how the virus enters cells and causes infection, according to Jordi Bella, a postdoctoral researcher at Purdue and lead author of the study. "Right now, we only know that the virus attaches to the cell and its genomic material is released," Bella explains. "The initial and end events are known, but the sequence of events in between is a mystery. Knowledge of the structure of ICAM-1 should help to shed light on the process of infection and perhaps suggest more effective therapeutic approaches to the common cold." The Purdue research team found that the tip of ICAM-1, unlike other cellular adhesion molecules, is shaped like a hand with a thumb and three fingers. Normally, white blood cells dispatched to help heal damaged cells bind to the thumblike projection. Rhinovirus, however, binds to the fingerlike projections to infect the cell. A Harvard Medical School research team independently reported on similar results in an article that appears in the same publication (J. M. Casasnovas et al., PNAS, 95:4134-4139, 1998). THE WEB UNWOVEN Internet searchers, if your key words or phrases too often return an unwieldy list of a thousand hits, Cornell University computer science professor Jon Kleinberg has a refinement for you. He has created an algorithm that analyzes the links among Web pages in any list found by a text-based search. "The mathematical structure is basically a method for propagating 'weights' across the web," Kleinberg says. The weights are scores of two types that are assigned to the sites. One score, for "authority," is based on how often the site is identified by other web pages. The other score, for a "hub," measures how many hyperlinks the site contains to other pages. Repetitions of this calculation whittle down the original list to highly focused groups of authorities and hubs. Kleinberg's method also "pools" its hubs and authorities into similar communities--for example, separating sites about the cat, car, and computer called "jaguar." In academic searches, a well-rated authority often doubles as an important hub. Such an overlap is not so evident in commercial sites, where competitors frequently fail to link to one another's pages. In those cases, the best hubs may be independent compilers or reviewers of authority sites. According to Kleinberg, "The technique can be made to run in real time," which probably means less than a minute for most searches. He refined his method, called HITS (Hyperlink-Induced Topic Search), while working recently as a visiting scientist at IBM, which has applied for a patent. AUTOIMMUNE, OR NOT Scleroderma--hardening and shrinking connective tissue in skin, blood vessels, and other organs--has long been considered an autoimmune condition. Researchers at Jefferson Medical College report that fetal cells may lie behind the illness (C.M. Artlett et al., New England Journal of Medicine, 338:1186-1191, 1998). The researchers suspected lurking fetal cells jump-starting a maternal immune response because scleroderma is much more common among older women who have had children; symptoms and autoantibodies resemble those of graft-vs.-host disease; and fetal blood cells often leak into the maternal circulation. They used fluorescence in situ hybridization to distinguish Y (red) from X (green) chromosomes in affected cells from seven women. (A female fetus could also cause this response, but is much harder to distinguish from maternal cells.) But fetal cells alone probably aren't enough to trigger scleroderma. "An environmental factor, such as a virus, radiation, or chemical, may activate these cells to become aggressive," says Sergio Jimenez, Dorrance H. Hamilton professor of medicine at Jefferson. And the discovery puts a new spin on the very concept of autoimmunity. "It opens the possibility that some autoimmune diseases are not really autoimmune. We think of these disorders as being self-aggression, but that might not always be the mechanism. Foreign cells can initiate the reaction. Other autoimmune disorders, such as lupus, may operate by this mechanism as well," he adds. LESS OVERSIGHT FOR BEAUTY DRUGS Cosmeceuticals, cosmetics with bioactive ingredients, may be on the rise (S. Bunk, The Scientist, 12[2]:1, Jan. 19, 1998), but efforts to regulate them are not. Budget cuts at the Food and Drug Administration has prompted the agency to slash the Office of Cosmetics and Colors (OCC) staff from 27 to 15. Citing inadequate laws and reduced resources, OCC director John Bailey worries that cosmeceuticals "are coming to market without a premarket review of safety or efficacy." As an example, he cites alpha-hydroxy acids, popular agents for ameliorating photodamage to skin, which he thinks might increase the risk of skin cancer. In response to the cuts, OCC has reduced or suspended testing for the presence of carcinogens such as nitrosamines and dioxanes in personal-care products, including shampoos and body lotions. The office is also halting a program in which companies voluntarily disclosed the ingredients in their products (40 percent to 50 percent of firms complied). To maintain safeguards to consumer health, Bailey says OCC will form stronger ties with FDA's Center for Drug Evaluation and Research, which is more enforcement-oriented. Informed of the OCC cuts, E. Edward Kavanaugh, president of the Washington, D.C.-based Cosmetic, Toiletry, and Fragrance Association, promptly asked the House appropriations subcommittee that oversees FDA to restore OCC funding to $5 million. The trade group has spoken with a number of congressmen, says Mike Petrina, vice president for legislative relations. Even if OCC staff levels are restored, observers agree that the political climate in Washington does not currently favor passage of new laws covering cosmeceuticals. Jacqueline K. Barton AWARD-WINNING DESIGN California Institute of Technology chemist Jacqueline K. Barton will receive the 1998 Weizmann Women & Science Award for her work in probing the chemistry of DNA. Barton designed small molecules that bind to specific DNA sites. Those molecules have allowed her to study the transport of electric charge through DNA. Experiments studying electrical charges have established reactions by which DNA can be damaged from a distance and suggested ways in which photochemical lesions in DNA might be repaired. The award, which includes a $25,000 research grant to the scientific project of the recipient's choice, is given to an outstanding woman scientist in the United States who has made a significant contribution. The objective of the award is to enhance the visibility of women in science, and to provide role models who will motivate and encourage the next generation of young women scientists (P. Smaglik, The Scientist, 11[23]:1, Nov. 24, 1997). Barton will receive the award June 2 at the New York Academy of Sciences.

Notebook

The Scientist Staff

May 10, 1998

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