Scientometrics

, Volume 101, Issue 1, pp 1–16 | Cite as

R&D dynamics and scientific breakthroughs in HIV/AIDS drugs development: the case of Integrase Inhibitors

Article

Abstract

Transformations and applications of scientific knowledge into new technologies are usually complex interactive processes. Is it possible to detect, from bibliographic information alone, structural alterations and significant events within these processes that may indicate breakthrough discoveries? In this empirical study we focus on R&D processes leading to HIV/AIDS medicines called Integrase Inhibitors. Where scientific progress and discoveries are reflected in research papers, patents signify inventions and technological achievements. Our temporal analysis of distinctive events in this R&D area, tracing trends within both bibliographic information sources, is driven by three bibliometric indicators: (1) contributions of ‘bridging researchers’ who are also inventors, (2) ‘key papers’ that subject experts in the field considered milestones in the research process, and (3) the multidisciplinary impact of those papers. The main results indicate that a combination of key papers, bridging researchers and multidisciplinary impact might help track potential ‘Charge type’ breakthrough developments.

Keywords

R&D dynamics HIV/AIDS drugs development Bridging researchers Scientific breakthroughs 

References

  1. Ahuja, G., & Lampert, C. M. (2001). Entrepreneurship in the large corporation: A longitudinal study of how established firms create breakthrough inventions. Strategic Management Journal, 22(6–7), 521–543.CrossRefGoogle Scholar
  2. Arbesman, S. (2010). Quantifying the ease of scientific discovery. Scientometrics, 86(2), 245–250.CrossRefGoogle Scholar
  3. Baba, M., Tanaka, H., De Clercq, E., Pauwels, R., Balzarini, J., Schols, D., et al. (1989). Highly specific-inhibition of human immunodeficiency virus type-1 by a novel 6-substituted acyclouridine derivative. Biochemical and Biophysical Research Communications, 165(3), 1375–1381.CrossRefGoogle Scholar
  4. Balconi, M., Breschi, S., & Lissoni, F. (2004). Networks of inventors and the role of academia: An exploration of Italian patent data. Research Policy, 33(1), 127–145.CrossRefGoogle Scholar
  5. Bettencourt, L., Kaiser, D., Kaur, J., Castillo-Chávez, C., & Wojick, D. (2008). Population modeling of the emergence and development of scientific fields. Scientometrics, 75(3), 495–518.CrossRefGoogle Scholar
  6. Breiner, S., Cuhls, K., & Grupp, H. (1994). Technology foresight using a Delphi approach—a Japanese-German cooperation. R & D management, 24(2), 141–153.CrossRefGoogle Scholar
  7. Chandy, R. K., & Tellis, G. J. (2000). The incumbent’s curse? incumbency, size, and radical product innovation. Journal of Marketing, 64(3), 1–17.CrossRefGoogle Scholar
  8. Chen, C. (2012). Predictive effects of structural variation on citation counts. Journal of the American Society for Information Science and Technology, 63(3), 431–449.CrossRefGoogle Scholar
  9. Chen, C., Chen, Y., Horowitz, M., Hou, H., Liu, Z., & Pellegrino, D. (2009). Towards an explanatory and computational theory of scientific discovery. Journal of Informetrics, 3(3), 191–209.CrossRefGoogle Scholar
  10. Ciechanover, A. (2009). Tracing the history of the ubiquitin proteolytic system: The pioneering article. Biochemical and Biophysical Research Communications, 387(1), 1–10.CrossRefGoogle Scholar
  11. Cockburn, I., & Henderson, R. (1998). Absorptive capacity. Coauthoring Behavior, and the Organization of Research in Drug Discovery, Journal of Industrial Economics, 46(2), 157–182.Google Scholar
  12. De Clercq, E. (2009). The history of antiretrovirals: key discoveries over the past 25 years. Reviews in Medical Virology, 19(5), 287–299.CrossRefGoogle Scholar
  13. De Clercq, E. (2013). Personal communication.Google Scholar
  14. Esté, J. A., & Telenti, A. (2007). HIV entry inhibitors. The Lancet, 370(9581), 81–88.CrossRefGoogle Scholar
  15. FDA (2004). Innovation or stagnation? challenge and opportunity on the critical path to new medical products. U.S. Department of Health and Human Services—Food and Drug Administration (FDA).Google Scholar
  16. Furukawa, R., & Goto, A. (2006). Core scientists and innovation in Japanese electronics companies. Scientometrics, 68(2), 227–240.CrossRefGoogle Scholar
  17. Grupp, H. (Ed.). (1992). Dynamics of science-based innovation. Berlin: Springer.Google Scholar
  18. Hazuda, D. J., Anthony, N. J., Jolly, R. P., Gomez, S. M., Wai, J. S., Zhuang, L., et al. (2004a). A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proceedings of the National Academy of Sciences of the United States of America, 101(31), 11233–11238.CrossRefGoogle Scholar
  19. Hazuda, D. J., Felock, P., Witmer, M., Wolfe, A., Stillmock, K., Grobler, J. A., et al. (2000). Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science, 287(5453), 646–650.CrossRefGoogle Scholar
  20. Hazuda, D. J., Young, S. D., Cuare, J. P., Anthony, N. J., Gomez, R. P., Wai, J. S., et al. (2004b). Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science, 305(5683), 528–532.CrossRefGoogle Scholar
  21. Henderson, R. M., & Clark, K. B. (1990). Architectural innovation: The reconfiguration of existing product technologies and the failure of established firms. Administrative Science Quarterly, 35(1), 9–30.CrossRefGoogle Scholar
  22. Hicks, D. (2000). 360 degree linkage analysis. Research Evaluation, 9(2), 133–143.CrossRefGoogle Scholar
  23. Hollingsworth, J. R. (2008). Scientific discoveries: An institutionalist and path-dependent perspective. In C. Hannaway (Ed.), Biomedicine in the twentieth century: Practices, policies, and politics (Vol. 72, pp. 317–353)., Biomedical and Health Research Amsterdam: IOS Press.Google Scholar
  24. IOM. (2009). Conflict of medical research, education, and practice. In B. Lo & M. J. Field (Eds.), Washington, DC: IOM—Institute of Medicine.Google Scholar
  25. Isenson, R. S. (1969). Project hindsight (final report) (Tech. Rep.). Technical Report AD495905, Office of the Director of Defense Research Engineering, Washington, DC, 20301.Google Scholar
  26. Jewkes, J., Sawers, D., & Stillerman, R. (1969). The sources of invention. London: MacMillan.Google Scholar
  27. Julius, M., Berkoff, E. C., Strack, A. E., Krasovec, F., & Bender, A. D. (1977). A very early warning system for the rapid identification and transfer of new technology. Journal of the American Society for Information Science, 28(3), 170–174.CrossRefGoogle Scholar
  28. Koshland, D. E. (2007). The Cha–Cha–Cha theory of scientific discovery. Science, 317(5839), 761–762.CrossRefGoogle Scholar
  29. Kuhn, T. S. (1962). The structure of scientific revolutions. Chicago: The University of Chicago Press.Google Scholar
  30. Lissoni, F. (2010). Academic inventors as brokers. Research Policy, 39(7), 843–857.CrossRefGoogle Scholar
  31. Luwel, M., & van Wijk, E. (2012). Publication delays revisited: 1998–2012. In E. Archambault, Y. Gingras and V. Larivière, (Eds.), Proceedings of the 17th International Conference on Science and Technology Indicators, volume 2, pp. 569–577.Google Scholar
  32. Martin, B. R. (1995). Foresight in science and technology. Technology Analysis and Strategic Management, 7(2), 139–168.CrossRefGoogle Scholar
  33. Meyer, M. (2006). Are patenting scientists the better scholars? An exploratory comparison of inventor-authors with their non-inventing peers in nano-science and technology. Research Policy, 35(10), 1646–1662.CrossRefGoogle Scholar
  34. Miyasaka, T., Tanaka, H., Baba, M., Hayakawa, H., Walker, R. T., Balzarini, J., et al. (1989). A novel lead for specific anti-hiv-1 agents: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. Journal of Medicinal Chemistry, 32(12), 2507–2509.CrossRefGoogle Scholar
  35. Narin, F., & Olivastro, D. (1998). Linkage between patents and papers: An interim EPO/US comparison. Scientometrics, 41, 51–59. doi:10.1007/BF02457966.CrossRefGoogle Scholar
  36. Noyons, E. C., Van Raan, A. F., Grupp, H., & Schmoch, U. (1994). Exploring the science and technology interface—inventor author relations in laser medicine research. Research Policy, 23(4), 443–457.CrossRefGoogle Scholar
  37. Pauwels, R., Andries, K., Desmyter, J., Schols, D., Kukla, M. J., Breslin, H. J., et al. (1990). Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature, 343(6257), 470–474.CrossRefGoogle Scholar
  38. Podolny, J. M., & Stuart, T. E. (1995). A role-based ecology of technological change. American Journal of Sociology, 100(5), 1224–1260.CrossRefGoogle Scholar
  39. Ponomarev, I., Williams, D., Lawton, B., Cross, D. H., Seger, Y., Schnell, J., and Haak, L. (2012). Breakthrough paper indicator: Early detection and measurement of ground-breaking research. In KG. Jeffery, J. Dvořák, (eds.): E-infrastructures for research and innovation: Linking information systems to improve scientific knowledge production: Proceedings of the 11th International Conference on Current Research Information Systems (June 6–9, 2012, Prague, Czech Republic), pp. 295–304. ISBN 978-80-86742-33-5.Google Scholar
  40. Porter, A., & Rafols, I. (2009). Is science becoming more interdisciplinary? measuring and mapping six research fields over time. Scientometrics, 81, 719–745.CrossRefGoogle Scholar
  41. Redner, S. (2005). Citation statistics from 110 years of Physical Review. Physics Today, 58(6), 49.CrossRefGoogle Scholar
  42. Roberts, N., Martin, J., Kinchington, D., Broadhurst, A., Craig, J., Duncan, I., et al. (1990). Rational design of peptide-based HIV proteinase inhibitors. Science, 248(4953), 358–361.CrossRefGoogle Scholar
  43. Rosenkopf, L., & Nerkar, A. (2001). Beyond local search: Boundary spanning, exploration and impact in the optical disk industry. Strategic Management Journal, 22(4), 287–306.CrossRefGoogle Scholar
  44. Small, H., and Klavans, R. (2011). Identifying scientific breakthroughs by combining co-citation analysis and citation context. In E. Noyons, P. Ngulube & J. Leta (Eds.), Proceedings of the 13th International Conference of the International Society for Scientometrics and Informatics (ISSI 2011), pp. 783–793.Google Scholar
  45. Stokes, D. (1997). Pasteur’s quadrant: Basic science and technological innovation. Washington, DC: Brookings Institute Press.Google Scholar
  46. Tijssen, R. J. W. (2002). Science dependence of technologies: evidence from inventions and their inventors. Research Policy, 31(4), 509–526.CrossRefGoogle Scholar
  47. Trajtenberg, M. (1990a). Economic analysis of product innovation: The case of CT scanners. Cambridge, MA: Harvard University Press.Google Scholar
  48. Trajtenberg, M. (1990b). A penny for your quotes: patent citations and the value of information. RAND Journal of Economics, 21, 325–342.CrossRefGoogle Scholar
  49. Tushman, M. L., & Anderson, P. (1986). Technological discontinuities and organizational environments. Administrative Science Quarterly, 31(3), 439–465.CrossRefGoogle Scholar
  50. Van Andel, P. (1994). Anatomy of the unsought finding serendipity: Origin, history, domains, traditions, appearances, patterns and programmability. The British Journal for the Philosophy of Science, 45(2), 631–648.CrossRefGoogle Scholar
  51. Wang, R., Gao, Y., & Lai, L. (2000). LigBuilder: A multi-purpose program for structure-based drug design. Journal of Molecular Modeling, 6(7–8), 498–516.CrossRefGoogle Scholar
  52. Wang, D., Song, C., & Barabási, A.-L. (2013). Quantifying long-term scientific impact. Science, 342(6154), 127–132.CrossRefGoogle Scholar
  53. Wild, C., Greenwell, T., & Matthews, T. (1993). A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell—cell fusion. AIDS Research and Human Retroviruses, 9(11), 1051–1053.CrossRefGoogle Scholar
  54. Zucker, L. G., & Darby, M. R. (1996). Star scientists and institutional transformation: Patterns of invention and innovation in the formation of the biotechnology industry. Proceedings of the National Academy of Sciences of the United States of America, 93(23), 2709–2716.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2014

Authors and Affiliations

  1. 1.Centre for Science and Technology Studies (CWTS)Leiden UniversityLeidenThe Netherlands
  2. 2.Leiden University Dual PhD Centre The HagueThe HagueThe Netherlands
  3. 3.Netherlands Patent Office (a Division of Netherlands Enterprise Agency)The HagueThe Netherlands
  4. 4.DST-NRF Centre of Excellence in Scientometrics and STI PolicyStellenbosch UniversityStellenboschSouth Africa

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