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simple organic chemicals.42 This is, of course, in contrast to most modi ed beta-lactams, whose production involves modi cation of fermentation-derived starting materials. A parallel program at Takeda led to the commercial monobactam carumonam.43 Pharmaceutical research in the early 1960s relied heavily on the output of its organic chemists. These individuals as a rule synthesized compounds that were aimed at some particular therapeutic target and were tested in a model for that disease. Surplus amounts of the samples were then tested in a standard screen. This usually comprised an array of tests that were designed to identify chemicals that showed some degree of biological activity in other disease models. The rationale for this procedure lay in the observation of the number of compounds that had been found over the years to have more activity on some unintended endpoint than their purported target. Some of the compounds discovered by the screening procedure had provided leads for agents that had gone on to become successful drugs. In that period, the Sterling Drug laboratories had a long-standing program on tropical disease. A compound, submitted by one of their chemists, George Lesher, showed unexpected activity in the ongoing antibacterial screen. According to one account this was a byproduct from the synthesis of an antimalarial drug.44,45 The chemical showed enough activity for further development. This drug, nalidixic acid (Fig. 16), was developed further and approved for use in treating urinary tract infections. The chemical structure of this little heralded antibiotic, it should be noted, incorporated all the necessary features that would be found in the later quinolones. The activity of this forerunner was quite modest and was apparently not enough to stimulate research in competing laboratories. Only a few additional

Throughout this book, I highlight the discipline and best practices of these market leaders in setting up and supporting their very visible international Web sites and underlying systems. So that you can learn from their experiences and from that of less successful companies, I also underscore the worst practices of globalization. In the sections that follow, I present two case studies Travelocity and Eastman Chemical and the process and practices that allowed them to address the needs of the Eighth Continent. These two companies represent archetypes of corporate efforts to address consumer (Travelocity) and business users (Eastman) on the global Internet. I also outline the domestic marketing opportunities created by global immigration. In all three cases and in numerous examples of other companies in the rest of the

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Brichory, F, et al, Proteomics-Based Identi cation of Protein Gene Product 95 as a Tumor Antigen that Induces a Humoral Immune Response in Lung Cancer, Cancer Res, 61, 7908 7912 (2001) Broder, S, et al, The human genome, In: Pharmacogenomics: The Search for Individualized Therapeutics (in press, 2002) Cole, ST, et al, Deciphering the Biology of Mycobacterium tuberculosis from the Complete Genome Sequence, Nature, 393, 537 544 (1998) Cole, ST, et al, Massive gene decay in the leprosy bacillus, Nature, 409, 1007 1011 (2001) Department of Health & Human Services Health Insurance Portability and Accessibility Act Privacy Regulations Fed Reg, 65, 82463 82829 (2000) Dhanasekaran, SM, et al, Delineation of Prognostic Biomarkers in Prostate Cancer, Nature, 412, 822 826 (2001) Druker, BJ, et al.

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, Ef cacy and Safety of a Speci c Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia, N Engl J Med, 344, 1031 1037 (2001) Eaton, DL, et al, Genetic Susceptibility, In Rom WN (ed), Environmental and Occupational Medicine, 3rd ed Philadelphia: Lippincott-Raven, pp 209 221 (1998) Evans, WE, and MV Relling, Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics, Science, 186, 487 491 (1999) Data also from Supplemental Table 1 at (wwwsciencemagorg/feature/data/1044449shl) Exner, CV, et al, Lesser Response to Angiotensin-Converting-Enzyme Inhibitor Therapy in Black as Compared with White Patients with Left Ventricular Dysfunction, N Engl J Med, 344, 1351 1357 (2001) Fleischmann, RD, et al, Whole-Genome Random Sequencing and Assembly of Haemophilus in uenzae Rd, Science, 269, 496 512 (1995) Fullilove, M.

, Comment: Abandoning Race as a Variable in Public Health Research an Idea Whose Time Has Come, Am J Publ Hlth, 88, 1297 1298 (1998) Garber, ME, et al, Diversity of Gene Expression in Adenocarcinoma of the Lung, Proc Natl Acad Sci USA, 98, 13784 13789 (2001) Giordano, TJ, et al, Organ-Speci c Molecular Classi cation of Primary Lung, Colon, and Ovarian Adenocarcinomas Using Gene Expression Pro les, Am J Pathol, 159, 1231 1238 (2001) Goldenberg, MM, Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer, Clin Ther, 21, 309 318 (1999) Gorre, ME, et al, Clinical Resistance to STI-571 Cancer Therapy Caused by BCRABL Gene Mutation or Ampli cation, Science, 293, 876 880 (2001) Hager, M (ed).

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