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Executive Summary

WELLCOME STUDYING REVERSE TRANSCRIPTASE IN SPACE; DEC. 18 SHUTTLE FLIGHT, scheduled for launch from Cape Canaveral, Florida will include a Wellcome Research Labs project to evaluate the three-dimensional structure of the enzyme. Burroughs Wellcome's Retrovir (AZT) is effective in treating AIDS because of its inhibitor effect on reverse transcriptase. The reverse transcriptase work will be one of 120 protein crystal growth experiments to be conducted on board the space shuttle Columbia. Previous space flight experiments have shown that crystals grown in a gravity-free environment are larger and higher in quality than those grown in Earth-bound laboratories. Upon the shuttle's return, X-ray crystallography will be used to determine the three-dimensional structure of the compound under study. The crystal growth experiments on the Columbia will be the sixth such studies conducted on space shuttle flights. The NASA project is being directed by Charles Bugg, PhD, director of the Center for Macromolecular Crystallography and a senior scientist at the University of Alabama at Birmingham. Initial evaluation of the experiments from the Columbia will be conducted at UAB upon the return of the space shuttle. In addition to reverse transcriptase, other crystals will be grown on the shuttle flight, including aldose reductase, which is being studied by BioCryst and the University of Alabama for its role in diabetic complications. Merck and ICI have been developing an aldose reductase inhibitor (ponalrestat) for several years in a long-term clinical development project. Other compounds under evaluation include phospholipase A-2, which is is being evaluated by Upjohn for its part in the function of the cell membrane as a means of developing new drugs for pain and inflammation, and porcine elastase, which is being studied by Vertex Pharmaceuticals for its association with emphysema. BioCryst is an R&D start-up formed to develop commercial applications of X-ray crystallography based in Birmingham, Ala. Vertex is a drug design R&D firm based in Cambridge, Mass. Pharmaceutical products involved in the crystal growing experiments include DuPont's anti-rejection drug cyclosporin A, SmithKline & French's antibiotic aridicin aglycone, Schering-Plough's gamma interferon, and Lilly's human growth hormone. Also on board are projects involving agricultural diseases and treatments. While similar protein crystal growth experiments have been conducted on six previous shuttle flights, the Dec. 18 mission is scheduled to remain in space for at least nine days, compared to less than three days for earlier flights. As a result, scientists will be able to grow crystals at lower temperatures, which is expected to improve results.

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