Science/Technology 20%, by-product iron oxide slurry and sodium chloride have been entirely eliminated, and wastewater has been cut 70%. Moreover, the accompanying gypsum that's produced not only is 38% less than before, but is of a quality that can be used directly by the cement industry. ' O n e of our aims is to develop an economical polycarbonate production method that needs no solvent and does not generate common salt as by-product/' remarks Karl Heinz Buchel, Bayer's board member responsible for corporate research and development. Most polycarbonate now is made by reacting the disodium salt of bisphenol-A with phosgene in an alkaline solution, and in the presence of solvent that isn't miscible with water. The unwanted salt presents producers with a disposal problem. "The polycarbonate production process will never be completely free of common salt until a way has been found of manufacturing diphenyl carbonate without using salt," Bûchel observes. "We already have a number of ideas of how this might be done. For example, hydrogen chloride generated by the reaction could be subjected to electrolysis instead of being neutralized to form salt. Chlorine could then be recycled for reuse in phosgene production. So, no chlorine or chlorine derivatives would leave the plant." Buchel also describes a novel Bayer method for preparing solid waste for storage that now is undergoing trials at Leverkusen. "It involves mixing the waste according to particle size and chemical composition, and compressing it into hard slabs of extremely low permeability and leachability," he says. "In our $2.7 million pilot plant, 50-sq-cm slabs are formed under pressures of up to 200 bar. These are stacked to form blocks, wrapped in plastic sheeting to make them dustproof and weatherproof, and deposited in our landfill site. In this way, the volume of solid waste can be reduced by about 30% compared to conventional landfills. Sealed at the top and sides by barrier layers, the compact landfill should ensure ecologically compatible, safe deposition of solid waste." D
Catalytic antibody functions in vivo An antibody that catalyzes a metabolically essential reaction—the conversion of chorismate into prephenate—is catalytically active in yeast cells and, to a limited extent, can replace the native enzyme that carries out this reaction, according to researchers at the Scripps Research Institute, La Jolla, Calif. This is the first experiment to demonstrate that catalytic antibodies can function in vivo, which could ultimately open up a variety of applications for such antibodies [Proc. Nat. Acad. Scl, 88, 8784 (1991)]. The research also potentially provides a selection assay for identifying subsequent changes in antibody molecules that augment their chemical efficiency, the Scripps researchers say. The research was carried out by Donald Hilvert, an associate professor in the departments of chemistry and molecular biology at Scripps; Ying Tang, a graduate student; and James B. Hicks, a yeast geneticist. The researchers introduce genetic elements that encode the Fab protein fragment of an antibody that has chorismate mutase activity into a strain of yeast in which the native chorismate mutase gene has been rendered inoperative. (A Fab fragment consists of the variable regions
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LONZA. Development. LONZA Inc., 17-17 Route 208 Fair Lawn, NJ 07410/USA, Telephone: 201-794-2400 Telex: 475-4539, Telefax: 201-794-2695 Headquarters L O N Z A LTD, Organic Chemicals CH-4002 Basle, Telephone: 061/316 8111 Telex: 965 960, Telefax: 061/316 83 01 Members of the A * L Alusuisse-Lonza Group
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October 21, 1991 C&EN
Science/Technology of both the heavy and light chains of an antibody and possesses the same binding affinity as the anti body itself.) The conversion of chorismate into prephenate is the key step in the biosynthesis of the aromatic amino acids tyrosine and phenylalanine. Yeast strains lacking chorismate mutase require a supply of these two amino acids for efficient growth. Simply introducing the catalytic an tibody into the chorismate mutase de ficient yeast strain does not, in itself, correct the deficiency, Hilvert says. Although high levels of the correctly assembled Fab are produced in the cy toplasm of the yeast cells, the cells still must be supplied with tyrosine and phenylalanine to grow. However, subsequent mutagene sis and selection of the yeast strain engineered to produce the choris mate mutase Fab produced a num ber of yeast cell lines that were able to grow in the absence of tyrosine and phenylalanine, Hilvert says. One of these was characterized in some detail, and a number of lines of evidence demonstrate that the mutase activity "plays an essential metabolic role" in the strain. Hilvert emphasizes that the mu tagenesis does not increase chemical efficiency of the chorismate mutase Fab. Rather, he says, the subsequent mutations "may reflect either im proved intracellular expression and/ or stability" of the antibody. Efforts are under way to establish the na ture of these mutations. Hilvert hopes to demonstrate that further rounds of mutagenesis do result in the evolution of the catalyt ic antibody toward greater chemical efficiency. Achieving this is impor tant because "first-generation" cata lytic antibodies are much less effi cient than natural enzymes and ge netic selection is the most promising route to increasing that efficiency. The experiments, Hilvert says, "establish the feasibility of directing eukaryotic cells to produce manmade catalysts not normally found in their evolutionary repertoire." This ability could provide scientists with a new tool for "regulating cel lular function, altering cellular me tabolism, and destroying toxins in vivo," he concludes. Rudy Baum
Chromosome paints ready to market A new biological technology devel oped at Lawrence Livermore Na tional Laboratory (LLNL) is behind the market launch this month of a research product called Whole Chro mosome Paints by Imagenetics, an Illinois-based medical diagnostics company. The technique, known as chromosome painting, uses specially developed fluorescent dyes to stain chromosomes. The potential exists to dramatical ly improve diagnosis and treatment followup of many cancers, accord ing to LLNL. With the paints, it says, researchers can more easily spot chromosome abnormalities, such as an extra chromosome or chromo some translocations, that are often indicative of cancer and leukemia. LLNL scientists had discovered that DNA and chemicals can be used to stain or "light u p " entire chromo somes within cells. Imagenetics de veloped an approach that allows dif ferent-colored fluorescent markers to be attached directly to DNA, an advance that permits simultaneous analysis of at least five different chromosomes. The company has also developed manufacturing pro cesses that have significantly re duced the cost of the reagents. Nine of the paints for the 24 hu man chromosomes will be available late this month and the remaining 15 within six to 12 months, accord ing to Imagenetics. They will be sold by Life Technologies Inc., Gaithersburg, Md. In staining chromosomes or subregions according to their DNA se quence, the DNA is heated to sepa rate the strands. The DNA to be studied is t h e n incubated w i t h chemically modified and denatured nucleic acid probe sequences that are complementary to DNA se quences in the chromosomes to be stained. In the past, LLNL explains, the bound probe was made visible by treatment with a fluorescent re agent able to bind to the probe's chemical modification. The Image netics advance eliminates this step, since the fluorescent markers are at tached directly to the DNA probes. James Krieger
