Table of Contents
Advances in Biology
Volume 2014 (2014), Article ID 278789, 20 pages
http://dx.doi.org/10.1155/2014/278789
Review Article

Translational Research: From Biological Discovery to Public Benefit (or Not)

Avoneaux Medical Institute, Oxford, MD 21654, USA

Received 18 February 2014; Revised 14 May 2014; Accepted 14 May 2014; Published 30 June 2014

Academic Editor: Dušan Kordiš

Copyright © 2014 Michael R. Emmert-Buck. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. E. Abraham, F. M. Marincola, Z. Chen, and X. Wang, “Clinical and translational medicine: integrative and practical science,” Clinical and Translational Medicine, vol. 1, article 1, 2012. View at Publisher · View at Google Scholar
  2. D. G. Contopoulos-Ioannidis, G. A. Alexiou, T. C. Gouvias, and J. P. A. Ioannidis, “Medicine: life cycle of translational research for medical interventions,” Science, vol. 321, no. 5894, pp. 1298–1299, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Hörig, E. Marincola, and F. M. Marincola, “Obstacles and opportunities in translational research,” Nature Medicine, vol. 11, no. 7, pp. 705–708, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. K. I. Kaitin and J. A. Dimasi, “Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000–2009,” Clinical Pharmacology and Therapeutics, vol. 89, no. 2, pp. 183–188, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. M. J. Khoury, M. Gwinn, and J. P. A. Ioannidis, “The emergence of translational epidemiology: from scientific discovery to population health impact,” American Journal of Epidemiology, vol. 172, no. 5, pp. 517–524, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. M. N. Liebman and F. M. Marincola, “Expanding the perspective of translational medicine: the value of observational data,” Journal of Translational Medicine, vol. 10, no. 1, article 61, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. A. M. Feldman, “Does academic culture support translational research?” Clinical and Translational Science, vol. 1, no. 2, pp. 87–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Scudellari, “The profits of nonprofit. The suprising results when drug development and altruism collide,” The Scientist, article 25, 2010. View at Google Scholar
  9. G. Will, Rev the scientific engine, Washington Post 2011.
  10. J. C. Greenwood, “Biotechnology: delivering on the promise,” Science Translational Medicine, vol. 2, no. 13, p. 13cm1, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. J. P. A. Ioannidis, “Materializing research promises: opportunities, priorities and conflicts in translational medicine,” Journal of Translational Medicine, vol. 2, article 5, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. S. P. Mankoff, C. Brander, S. Ferrone, and F. M. Marincola, “Lost in translation: obstacles to translational medicine,” Journal of Translational Medicine, vol. 2, article 14, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. F. M. Marincola, “The trouble with translational medicine,” Journal of Internal Medicine, vol. 270, no. 2, pp. 123–127, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. R. B. Nussenblatt, F. M. Marincola, and A. N. Schechter, “Translational Medicine—doing it backwards,” Journal of Translational Medicine, vol. 8, article 12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. J. S. Pober, C. S. Neuhauser, and J. M. Pober, “Obstacles facing translational research in academic medical centers,” FASEB Journal, vol. 15, no. 13, pp. 2303–2313, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Hay, D. W. Thomas, J. L. Craighead, C. Economides, and J. Rosenthal, “Clinical development success rates for investigational drugs,” Nature Biotechnology, vol. 32, pp. 40–51, 2014. View at Publisher · View at Google Scholar
  17. I. G. Mills and R. B. Sykes, “Taking risks with translational research,” Science Translational Medicine, vol. 2, no. 24, p. 24cm10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. M. R. Emmert-Buck, “An NIH intramural percubator as a model of academic-industry partnerships: from the beginning of life through the valley of death,” Journal of Translational Medicine, vol. 9, article 54, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Kaiser, “Rejecting 'big science' tag, collins sets five themes for NIH,” Science, vol. 325, no. 5943, p. 927, 2009. View at Google Scholar · View at Scopus
  20. B. H. Littman, L. di Mario, M. Plebani, and F. M. Marincola, “What's next in translational medicine?” Clinical Science, vol. 112, no. 3-4, pp. 217–227, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. X. Wu, F. M. Marincola, M. N. Liebman, and X. Wang, “A global resource to translational medicine: the International Park of Translational Medicine and BioMedicine (IPTBM),” Journal of Translational Medicine, vol. 11, no. 1, article 8, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. T. A. Golper and H. I. Feldman, “New challenges and paradigms for mid-career faculty in academic medical centers: key strategies for success for mid-career medical school faculty,” Clinical Journal of the American Society of Nephrology, vol. 3, no. 6, pp. 1870–1874, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. E. Dolgin, “Collins sets out his vision for the NIH,” Nature, vol. 460, no. 7258, p. 939, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Skarke and G. A. FitzGerald, “Training translators for smart drug discovery,” Science Translational Medicine, vol. 2, no. 26, p. 26cm12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. S. H. Woolf, “The meaning of translational research and why it matters,” Journal of the American Medical Association, vol. 299, no. 2, pp. 211–213, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. D. M. Rubio, E. E. Schoenbaum, L. S. Lee et al., “Defining translational research: implications for training,” Academic Medicine, vol. 85, no. 3, pp. 470–475, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Fleming, “On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae,” Reviews of Infectious Diseases, vol. 2, no. 1, pp. 129–139, 1980. View at Google Scholar · View at Scopus
  28. F. Diggins, The True History of the Discovery of Penicillin by Alexander Fleming, Biomedical Scientist, Insititute of Biomedical Sciences, London, 2003, Originally published in the Imperial College School of Medicine Gazette.
  29. I. Murray, “Paulescu and the isolation of insulin,” Journal of the History of Medicine and Allied Sciences, vol. 26, pp. 150–157, 1971. View at Google Scholar
  30. P. G. Katsoyannis, K. Fukuda, A. Tometsko, K. Suzuki, and M. Tilak, “The synthesis of the B-chain of insulin and its combination with natural or synthetic A-chain to generate insulin activity,” Journal of the American Chemical Society, vol. 86, no. 5, pp. 930–932, 1964. View at Google Scholar · View at Scopus
  31. F. G. Banting, J. B. Collip, W. R. Campbell, and A. A. Fletcher, “Pancreatic extracts in the treatment of diabetes mellitus,” Canadian Medical Association Journal, vol. 12, pp. 141–146, 1922. View at Google Scholar
  32. A. Wollmer, M. Federwisch, and P. de Meyts, Insulin & Related Proteins Structure to Function and Pharmacology, Kluwer Academic Publishers, Boston, Mass, USA, 2002.
  33. M. F. Dunn, “Zinc-ligand interactions modulate assembly and stability of the insulin hexamer—a review,” BioMetals, vol. 18, no. 4, pp. 295–303, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. B. T. Layden and W. L. Lowe Jr., “G-protein-coupled receptors, pancreatic islets, and diabetes,” Nature Education, vol. 3, article 13, 2010. View at Google Scholar
  35. D. X. Brown, E. L. Butler, and M. Evans, “Lixisenatide as add-on therapy to basal insulin,” Drug Design, Development and Therapy, vol. 8, pp. 25–38, 2013. View at Google Scholar
  36. D. Constantin-Teodosiu, “Regulation of muscle pyruvate dehydrogenase complex in insulin resistance: effects of exercise and dichloroacetate,” Diabetes and Metabolism Journal, vol. 37, pp. 301–314, 2013. View at Publisher · View at Google Scholar
  37. A. King, “Integrating advances in insulin into clinical practice: advances In insulin formulations,” The Journal of Family Practice, vol. 62, pp. S9–S17, 2013. View at Google Scholar
  38. C. Maria Rotella, L. Pala, and E. Mannucci, “Role of insulin in the type 2 diabetes therapy: past, present and future,” International Journal of Endocrinology and Metabolism, vol. 11, pp. 137–144, 2013. View at Google Scholar
  39. K. M. A. Gartland, F. Bruschi, M. Dundar, P. B. Gahan, M. P. Viola Magni, and Y. Akbarova, “Progress towards the 'Golden Age' of biotechnology,” Current Opinion in Biotechnology, vol. 24, no. 1, pp. S6–S13, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. B. M. Silber, “Driving drug discovery: the fundamental role of academic labs,” Science Translational Medicine, vol. 2, no. 30, p. 30cm16, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. A. J. Stevens, J. J. Jensen, K. Wyller, P. C. Kilgore, S. Chatterjee, and M. L. Rohrbaugh, “The role of public-sector research in the discovery of drugs and vaccines,” The New England Journal of Medicine, vol. 364, no. 6, pp. 535–541, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. K. Debackere and R. Veugelers, “The role of academic technology transfer organizations in improving industry science links,” Research Policy, vol. 34, no. 3, pp. 321–342, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. A. M. Boccanfuso, “Why university-industry partnerships matter,” Science Translational Medicine, vol. 2, no. 51, p. 51cm25, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Evans and F. Austin, “Collaborations among academia, government, and industry in the diagnostics space: barriers and some ideas for solutions,” Science Translational Medicine, vol. 2, no. 63, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. L. M. Portilla and B. Alving, “Reaping the benefits of biomedical research: partnerships required,” Science Translational Medicine, vol. 2, no. 35, p. 35cm17, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Handelsman, “A translational research niche for small business innovation research grants,” Science Translational Medicine, vol. 1, no. 5, p. 5cm6, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. R. Klausner, “Translational science: a view from a biotechnology investor,” Science Translational Medicine, vol. 2, no. 34, p. 34ed3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. L. Serrano, “Synthetic biology: promises and challenges,” Molecular Systems Biology, vol. 3, article 158, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. H. O. Smith, C. A. Hutchison III, C. Pfannkoch, and J. C. Venter, “Generating a synthetic genome by whole genome assembly: φX174 bacteriophage from synthetic oligonucleotides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15440–15445, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. D. J. Segal and J. F. Meckler, “Genome engineering at the dawn of the golden age,” Annual Review of Genomics and Human Genetics, vol. 14, pp. 135–158, 2013. View at Publisher · View at Google Scholar
  51. L.-Y. Zhang, S.-H. Chang, and J. Wang, “How to make a minimal genome for synthetic minimal cell,” Protein & Cell, vol. 1, no. 5, pp. 427–434, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. O'Malley, A. Powell, J. F. Davies, and J. Calvert, “Knowledge-making distinctions in synthetic biology,” BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, vol. 30, no. 1, pp. 57–65, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. D. Balke, C. Wichert, B. Appel, and S. Muller, “Generation and selection of ribozyme variants with potential application in protein engineering and synthetic biology,” Applied Microbiology and Biotechnology, vol. 98, no. 8, pp. 3389–3399, 2014. View at Google Scholar
  54. H. Ye, D. Aubel, and M. Fussenegger, “Synthetic mammalian gene circuits for biomedical applications,” Current Opinion in Chemical Biology, vol. 17, no. 6, pp. 910–917, 2013. View at Publisher · View at Google Scholar
  55. A. V. Bryksin, A. C. Brown, M. M. Baksh, M. G. Finn, and T. H. Barker, “Learning from nature-novel synthetic biology approaches for biomaterial design,” Acta Biomaterialia, vol. 10, no. 4, pp. 1761–1769, 2014. View at Google Scholar
  56. V. Singh, “Recent advancements in synthetic biology: current status and challenges,” Gene, vol. 535, pp. 1–11, 2014. View at Publisher · View at Google Scholar
  57. C. M. Agapakis, “Designing synthetic biology,” ACS Synthetic Biology, vol. 3, no. 3, pp. 121–128, 2014. View at Publisher · View at Google Scholar
  58. L. B. Scharff and R. Bock, “Emerging tools for synthetic biology in plants,” The Plant Journal, vol. 78, no. 5, pp. 783–798, 2014. View at Publisher · View at Google Scholar
  59. R. Rekhi and A. A. Qutub, “Systems approaches for synthetic biology: a pathway toward mammalian design,” Frontiers in Physiology, vol. 4, article 285, 2013. View at Google Scholar
  60. K. H. Lee and D. M. Kim, “Applications of cell-free protein synthesis in synthetic biology: interfacing bio-machinery with synthetic environments,” Biotechnology Journal, vol. 8, no. 11, pp. 1292–1300, 2013. View at Google Scholar
  61. H. Kim and E. Gelenbe, “G-networks towards synthetic biology: a brief review,” in Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference, pp. 579–583, 2013.
  62. W. Bacchus, D. Aubel, and M. Fussenegger, “Biomedically relevant circuit-design strategies in mammalian synthetic biology,” Molecular Systems Biology, vol. 9, article 691, 2013. View at Google Scholar
  63. M. Kalos and C. H. June, “Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology,” Immunity, vol. 39, no. 1, pp. 49–60, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. B.-R. Lee, S. Cho, Y. Song, S. C. Kim, and B.-K. Cho, “Emerging tools for synthetic genome design,” Molecules and Cells, vol. 35, no. 5, pp. 359–370, 2013. View at Publisher · View at Google Scholar · View at Scopus
  65. J. A. J. Arpino, E. J. Hancock, J. Anderson et al., “Tuning the dials of synthetic biology,” Microbiology, vol. 159, no. 7, pp. 1236–1253, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. M. G. J. de Vos, F. J. Poelwijk, and S. J. Tans, “Optimality in evolution: New insights from synthetic biology,” Current Opinion in Biotechnology, vol. 24, no. 4, pp. 797–802, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. J. A. Gimpel, E. A. Specht, D. R. Georgianna, and S. P. Mayfield, “Advances in microalgae engineering and synthetic biology applications for biofuel production,” Current Opinion in Chemical Biology, vol. 17, no. 3, pp. 489–495, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. B. J. Karas, B. Molparia, J. Jablanovic et al., “Assembly of eukaryotic algal chromosomes in yeast,” Journal of Biological Engineering, vol. 7, article 30, 2013. View at Publisher · View at Google Scholar
  69. M. G. Montague, C. Lartigue, and S. Vashee, “Synthetic genomics: potential and limitations,” Current Opinion in Biotechnology, vol. 23, no. 5, pp. 659–665, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. J. I. Glass, N. Assad-Garcia, N. Alperovich et al., “Essential genes of a minimal bacterium,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 2, pp. 425–430, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. E. Pennisi, “Venter cooks up a synthetic genome in record time,” Science, vol. 302, no. 5649, article 1307, 2003. View at Google Scholar · View at Scopus
  72. M. Schmidt, H. Torgersen, A. Ganguli-Mitra, A. Kelle, A. Deplazes, and N. Biller-Andorno, “SYNBIOSAFE e-conference: online community discussion on the societal aspects of synthetic biology,” Systems and Synthetic Biology, vol. 2, no. 1-2, pp. 7–17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Kelle, “Ensuring the security of synthetic biology-towards a 5p governance strategy,” Systems and Synthetic Biology, vol. 3, no. 1, pp. 85–90, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Joly, G. Koutrikas, A.-M. Tassé et al., “Regulatory approval for new pharmacogenomic tests: A comparative overview,” Food and Drug Law Journal, vol. 66, no. 1, pp. 1–24, 2011. View at Google Scholar · View at Scopus
  75. S. H. Yim and Y. J. Chung, “Introduction to international ethical standards related to genetics and genomics,” Genomics & Informatics, vol. 11, pp. 218–223, 2013. View at Google Scholar
  76. E. Shapiro, T. Biezuner, and S. Linnarsson, “Single-cell sequencing-based technologies will revolutionize whole-organism science,” Nature Reviews Genetics, vol. 14, no. 9, pp. 618–630, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. C. H. Wade, B. A. Tarini, and B. S. Wilfond, “Growing up in the genomic era: implications of whole-genome sequencing for children, families, and pediatric practice,” Annual Review of Genomics and Human Genetics, vol. 14, pp. 535–555, 2013. View at Google Scholar
  78. T. Pang, “Genomics for public health improvement: relevant international ethical and policy issues around genome-wide association studies and biobanks,” Public Health Genomics, vol. 16, no. 1-2, pp. 69–72, 2013. View at Publisher · View at Google Scholar · View at Scopus
  79. E. R. Mardis, “Next-generation sequencing platforms,” Annual Review of Analytical Chemistry, vol. 6, pp. 287–303, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. B. Dan and P. Baxter, “Paediatric neurology: a year of DNA technology,” Lancet Neurology, vol. 13, pp. 16–18, 2014. View at Publisher · View at Google Scholar
  81. V. G. Sankaran and P. G. Gallagher, “Applications of high-throughput DNA sequencing to benign hematology,” Blood, vol. 122, pp. 3575–3582, 2013. View at Google Scholar
  82. Y. Yang, R. Liu, H. Xie et al., “Advances in nanopore sequencing technology,” Journal of Nanoscience and Nanotechnology, vol. 13, no. 7, pp. 4521–4538, 2013. View at Publisher · View at Google Scholar · View at Scopus
  83. R. Normand and I. Yanai, “An introduction to high-throughput sequencing experiments: design and bioinformatics analysis,” Methods in Molecular Biology, vol. 1038, pp. 1–26, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. F. S. Ong, J. C. Lin, K. Das, D. S. Grosu, and J.-B. Fan, “Translational utility of next-generation sequencing,” Genomics, vol. 102, no. 3, pp. 137–139, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Levy-Sakin and Y. Ebenstein, “Beyond sequencing: optical mapping of DNA in the age of nanotechnology and nanoscopy,” Current Opinion in Biotechnology, vol. 24, no. 4, pp. 690–698, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. J. F. Thompson and J. S. Oliver, “Mapping and sequencing DNA using nanopores and nanodetectors,” Electrophoresis, vol. 33, no. 23, pp. 3429–3436, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. B. Merriman, I. Torrent, and J. M. Rothberg, “Progress in ion torrent semiconductor chip based sequencing,” Electrophoresis, vol. 33, no. 23, pp. 3397–3417, 2012. View at Publisher · View at Google Scholar · View at Scopus
  88. M. Tuna and C. I. Amos, “Genomic sequencing in cancer,” Cancer Letters, vol. 340, pp. 161–170, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. S. Fox, S. Filichkin, and T. C. Mockler, “Applications of ultra-high-throughput sequencing,” Methods in Molecular Biology, vol. 553, pp. 79–108, 2009. View at Google Scholar · View at Scopus
  90. Y. Bromberg, “Building a Genome Analysis Pipeline to Predict Disease Risk and Prevent Disease,” Journal of Molecular Biology, vol. 425, pp. 3993–4005, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. J. M. Johnsen, D. A. Nickerson, and A. P. Reiner, “Massively parallel sequencing: the new frontier of hematologic genomics,” Blood, vol. 122, pp. 3268–3275, 2013. View at Google Scholar
  92. D. C. Koboldt, K. M. Steinberg, D. E. Larson, R. K. Wilson, and E. R. Mardis, “The next-generation sequencing revolution and its impact on genomics,” Cell, vol. 155, pp. 27–38, 2013. View at Google Scholar
  93. I. R. Watson, K. Takahashi, P. A. Futreal, and L. Chin, “Emerging patterns of somatic mutations in cancer,” Nature Reviews Genetics, vol. 14, pp. 703–718, 2013. View at Google Scholar
  94. L. Wang and D. A. Wheeler, “Genomic sequencing for cancer diagnosis and therapy,” Annual Review of Medicine, vol. 65, pp. 33–48, 2014. View at Google Scholar
  95. Y. R. Li, J. E. Levine, H. Hakonarson, and B. J. Keating, “Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation,” European Journal of Human Genetics, vol. 22, pp. 715–723, 2014. View at Publisher · View at Google Scholar
  96. K. Davies, “The era of genomic medicine,” Clinical Medicine, vol. 13, pp. 594–601, 2013. View at Google Scholar
  97. E. K. Bancroft, “How advances in genomics are changing patient care,” The Nursing Clinics of North America, vol. 48, pp. 557–569, 2013. View at Google Scholar
  98. F. B. de Abreu, W. A. Wells, and G. J. Tsongalis, “The emerging role of the molecular diagnostics laboratory in breast cancer personalized medicine,” The American Journal of Pathology, vol. 183, pp. 1075–1083, 2013. View at Google Scholar
  99. L. G. Biesecker, “Hypothesis-generating research and predictive medicine,” Genome Research, vol. 23, no. 7, pp. 1051–1053, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. S. Kamalakaran, V. Varadan, A. Janevski et al., “Translating next generation sequencing to practice: opportunities and necessary steps,” Molecular Oncology, vol. 7, no. 4, pp. 743–755, 2013. View at Publisher · View at Google Scholar · View at Scopus
  101. J. J. McCarthy, H. L. McLeod, and G. S. Ginsburg, “Genomic medicine: a decade of successes, challenges, and opportunities,” Science Translational Medicine, vol. 5, no. 189, p. 189sr4, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. R. Simon and S. Roychowdhury, “Implementing personalized cancer genomics in clinical trials,” Nature Reviews Drug Discovery, vol. 12, no. 5, pp. 358–369, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. L. A. Garraway, “Genomics-driven oncology: framework for an emerging paradigm,” Journal of Clinical Oncology, vol. 31, no. 15, pp. 1806–1814, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Tsuji, “The neurogenomics view of neurological diseases,” JAMA Neurology, vol. 70, no. 6, pp. 689–694, 2013. View at Publisher · View at Google Scholar · View at Scopus
  105. M. J. Annala, B. C. Parker, W. Zhang, and M. Nykter, “Fusion genes and their discovery using high throughput sequencing,” Cancer Letters, vol. 340, pp. 192–200, 2013. View at Publisher · View at Google Scholar · View at Scopus
  106. R. R. Gullapalli, K. V. Desai, L. Santana-Santos, J. A. Kant, and M. J. Becich, “Next generation sequencing in clinical medicine: challenges and lessons for pathology and biomedical informatics,” Journal of Pathology Informatics, vol. 3, article 40, 2012. View at Google Scholar
  107. C. Brander and F. M. Marincola, “AAAS joins the Translational Medicine family,” Journal of Translational Medicine, vol. 7, article 32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. X. Chen, R. Andersson, W. C. Cho et al., “The international effort: building the bridge for translational medicine: report of the 1st International Conference of Translational Medicine (ICTM),” Clinical and Translational Medicine, vol. 1, no. 1, article 15, 2012. View at Publisher · View at Google Scholar
  109. J. A. DiMasi, R. W. Hansen, H. G. Grabowski, and L. Lasagna, “Cost of innovation in the pharmaceutical industry,” Journal of Health Economics, vol. 10, no. 2, pp. 107–142, 1991. View at Publisher · View at Google Scholar · View at Scopus
  110. J. A. DiMasi, R. W. Hansen, and H. G. Grabowski, “The price of innovation: new estimates of drug development costs,” Journal of Health Economics, vol. 22, no. 2, pp. 151–185, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. M. E. Hughes, J. Peeler, and J. B. Hogenesch, “Network dynamics to evaluate performance of an academic institution,” Science Translational Medicine, vol. 2, no. 53, Article ID 53ps49, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. M. Qian, D. Wu, E. Wang et al., “Development and promotion in translational medicine: perspectives from 2012 sino-american symposium on clinical and translational medicine,” Clinical and Translational Medicine, vol. 1, article 25, 2012. View at Google Scholar
  113. A. Cambrosio, P. Keating, S. Mercier, G. Lewison, and A. Mogoutov, “Mapping the emergence and development of translational cancer research,” European Journal of Cancer, vol. 42, no. 18, pp. 3140–3148, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. A. Rajan, R. Sullivan, S. Bakker, and W. H. van Harten, “Critical appraisal of translational research models for suitability in performance assessment of cancer centers,” The Oncologist, vol. 17, no. 12, pp. e48–e57, 2012. View at Publisher · View at Google Scholar · View at Scopus
  115. W. Trochim, C. Kane, M. J. Graham, and H. A. Pincus, “Evaluating translational research: a process marker model,” Clinical and Translational Science, vol. 4, no. 3, pp. 153–162, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. E. A. Zerhouni, “Space for the cures: science launches a new journal dedicated to translational research in biomedicine,” Science Translational Medicine, vol. 1, no. 1, p. 1ed1, 2009. View at Publisher · View at Google Scholar · View at Scopus
  117. E. G. Nabel, “On board with the cures acceleration network,” Science Translational Medicine, vol. 2, no. 32, p. 32ed2, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. H. J. Falk-Krzesinski, K. Börner, N. Contractor et al., “Advancing the science of team science,” Clinical and Translational Science, vol. 3, no. 5, pp. 263–266, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. K. Börner, N. Contractor, H. J. Falk-Krzesinski et al., “A multi-level systems perspective for the science of team science,” Science Translational Medicine, vol. 2, no. 49, p. 49cm24, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. D. C. Mowery, B. N. Sampat, and A. A. Ziedonis, “Learning to patent: institutional experience, learning, and the characteristics of U.S. University patents after the Bayh-Dole Act, 1981–1992,” Management Science, vol. 48, no. 1, pp. 73–89, 2002. View at Google Scholar · View at Scopus
  121. V. Loise and A. J. Stevens, “The Bayh-Dole act turns 30,” Science Translational Medicine, vol. 2, no. 52, p. 52cm27, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. A. Colaianni and R. Cook-Deegan, “Columbia university's axel patents: technology transfer and implications for the Bayh-Dole Act,” Milbank Quarterly, vol. 87, no. 3, pp. 683–715, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. R. Dalton, “Berkeley's energy deal with BP sparks unease,” Nature, vol. 445, no. 7129, pp. 688–689, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. R. Jensen and M. Thursby, “Proofs and prototypes for sale: the licensing of University inventions,” The American Economic Review, vol. 91, no. 1, pp. 240–259, 2001. View at Google Scholar · View at Scopus
  125. S. A. Mian, “US university-sponsored technology incubators: an overview of management, policies and performance,” Technovation, vol. 14, no. 8, pp. 515–528, 1994. View at Google Scholar · View at Scopus
  126. N. R. Council, Managing University Intellectual Property in the Public Interest, The National Academies Press, Washington, DC, USA, 2010.
  127. R. G. Phillips, “Technology business incubators: how effective as technology transfer mechanisms?” Technology in Society, vol. 24, no. 3, pp. 299–316, 2002. View at Publisher · View at Google Scholar · View at Scopus
  128. J. Gertner, The Idea Factory: Bell Labs and the Great Age of American Innovation, Penguin, New York, NY, USA, 2012.
  129. M. Riordan and L. Hoddeson, Crystal Fire: the Invention of the Transistor and Birth of the Information Age, WW Norton, New York, NY, USA, 1998.
  130. W. F. Brinkman, D. E. Haggan, and W. W. Troutman, “A history of the invention of the transistor and where it will lead us,” IEEE Journal of Solid-State Circuits, vol. 32, no. 12, pp. 1858–1864, 1997. View at Publisher · View at Google Scholar · View at Scopus
  131. S. J. Steele, “Working with the CTSA consortium: what we bring to the table,” Science Translational Medicine, vol. 2, no. 63, p. 63mr5, 2010. View at Publisher · View at Google Scholar · View at Scopus
  132. J. G. Thursby and M. C. Thursby, “Intellectual property. University licensing and the Bayh-Dole Act,” Science, vol. 301, no. 5636, p. 1052, 2003. View at Google Scholar · View at Scopus
  133. D. Blumenthal, E. G. Campbell, N. Causino, and K. S. Louis, “Participation of life science faculty in research relationships with industry,” The New England Journal of Medicine, vol. 335, no. 23, pp. 1734–1739, 1996. View at Publisher · View at Google Scholar · View at Scopus
  134. R. Fini, N. Lacetera, and S. Shane, “Inside or outside the IP system? Business creation in academia,” Research Policy, vol. 39, no. 8, pp. 1060–1069, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. R. A. Lowe and C. Gonzalez-Brambila, “Faculty entrepreneurs and research productivity,” Journal of Technology Transfer, vol. 32, no. 3, pp. 173–194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. A. Aneja, R. Esquitin, K. Shah et al., “Authors' self-declared financial conflicts of interest do not impact the results of major cardiovascular trials,” Journal of the American College of Cardiology, vol. 61, pp. 1137–1143, 2013. View at Publisher · View at Google Scholar · View at Scopus
  137. S. V. Sharma, D. A. Haber, and J. Settleman, “Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents,” Nature Reviews Cancer, vol. 10, no. 4, pp. 241–253, 2010. View at Publisher · View at Google Scholar · View at Scopus
  138. J. Mattern, M. Bak, E. W. Hahn, and M. Volm, “Human tumor xenografts as model for drug testing,” Cancer Metastasis Reviews, vol. 7, no. 3, pp. 263–284, 1988. View at Publisher · View at Google Scholar · View at Scopus
  139. J. N. Weinstein, “Drug discovery: cell lines battle cancer,” Nature, vol. 483, no. 7391, pp. 544–545, 2012. View at Publisher · View at Google Scholar · View at Scopus
  140. R. H. Shoemaker, “The NCI60 human tumour cell line anticancer drug screen,” Nature Reviews Cancer, vol. 6, no. 10, pp. 813–823, 2006. View at Publisher · View at Google Scholar · View at Scopus
  141. U. McDermott, S. V. Sharma, and J. Settleman, “High-throughput lung cancer cell line screening for genotype-correlated sensitivity to an EGFR kinase inhibitor,” Methods in Enzymology, vol. 438, pp. 331–341, 2008. View at Publisher · View at Google Scholar · View at Scopus
  142. J. Barretina, G. Caponigro, N. Stransky et al., “Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity,” Nature, vol. 483, pp. 603–607, 2012. View at Publisher · View at Google Scholar · View at Scopus
  143. G. Kari, U. Rodeck, and A. P. Dicker, “Zebrafish: an emerging model system for human disease and drug discovery,” Clinical Pharmacology and Therapeutics, vol. 82, no. 1, pp. 70–80, 2007. View at Publisher · View at Google Scholar · View at Scopus
  144. C. Chakraborty, C. H. Hsu, Z. H. Wen, C. S. Lin, and G. Agoramoorthy, “Zebrafish: a complete animal model for in vivo drug discovery and development,” Current Drug Metabolism, vol. 10, no. 2, pp. 116–124, 2009. View at Publisher · View at Google Scholar · View at Scopus
  145. S. B. Hedges, “The origin and evolution of model organisms,” Nature Reviews Genetics, vol. 3, no. 11, pp. 838–849, 2002. View at Publisher · View at Google Scholar · View at Scopus
  146. M. Jucker, “The benefits and limitations of animal models for translational research in neurodegenerative diseases,” Nature Medicine, vol. 16, no. 11, pp. 1210–1214, 2010. View at Publisher · View at Google Scholar · View at Scopus
  147. C. G. Begley and L. M. Ellis, “Drug development: raise standards for preclinical cancer research,” Nature, vol. 483, no. 7391, pp. 531–533, 2012. View at Publisher · View at Google Scholar · View at Scopus
  148. D. Alishekevitz, R. Bril, D. Loven et al., “Differential therapeutic effects of anti-VEGF-A antibody in different tumor models: implications for choosing appropriate tumor models for drug testing,” Molecular Cancer Therapeutics, vol. 13, pp. 202–213, 2014. View at Publisher · View at Google Scholar
  149. J.-P. Gillet, S. Varma, and M. M. Gottesman, “The clinical relevance of cancer cell lines,” Journal of the National Cancer Institute, vol. 105, no. 7, pp. 452–458, 2013. View at Publisher · View at Google Scholar · View at Scopus
  150. A. F. Gazdar, B. Gao, and J. D. Minna, “Lung cancer cell lines: useless artifacts or invaluable tools for medical science?” Lung Cancer, vol. 68, no. 3, pp. 309–318, 2010. View at Publisher · View at Google Scholar · View at Scopus
  151. A. F. Gazdar, L. Girard, W. W. Lockwood, W. L. Lam, and J. D. Minna, “Lung cancer cell lines as tools for biomedical discovery and research,” Journal of the National Cancer Institute, vol. 102, no. 17, pp. 1310–1321, 2010. View at Publisher · View at Google Scholar · View at Scopus
  152. J. Gandhi, J. Zhang, Y. Xie et al., “Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines,” PLoS ONE, vol. 4, no. 2, Article ID e4576, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. J. L. Wilding and W. F. Bodmer, “Cancer cell lines for drug discovery and development,” Cancer Research, vol. 74, pp. 2377–2384, 2014. View at Google Scholar
  154. J. Heyer, L. N. Kwong, S. W. Lowe, and L. Chin, “Non-germline genetically engineered mouse models for translational cancer research,” Nature Reviews Cancer, vol. 10, no. 7, pp. 470–480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  155. K. Garber, “From human to mouse and back: “tumorgraft” models surge in popularity,” Journal of the National Cancer Institute, vol. 101, no. 1, pp. 6–8, 2009. View at Publisher · View at Google Scholar · View at Scopus
  156. S. Rottenberg and P. Borst, “Drug resistance in the mouse cancer clinic,” Drug Resistance Updates, vol. 15, no. 1-2, pp. 81–89, 2012. View at Publisher · View at Google Scholar · View at Scopus
  157. H. C. Denroche, W. L. Quong, J. E. Bruin et al., “Leptin administration enhances islet transplant performance in diabetic mice,” Diabetes, vol. 62, pp. 2738–2746, 2013. View at Google Scholar
  158. H. Dong, H. Huang, X. Yun et al., “Bilirubin increases insulin sensitivity in leptin-receptor deficient and diet-induced obese mice through suppression of ER stress and chronic inflammation,” Endocrinology, vol. 155, no. 3, pp. 818–828, 2014. View at Google Scholar
  159. U. H. Neumann, S. Chen, Y. Y. Tam et al., “IGFBP2 is neither sufficient nor necessary for the physiological actions of leptin on glucose homeostasis in male ob/ob mice,” Endocrinology, vol. 155, no. 3, pp. 16–25, 2014. View at Publisher · View at Google Scholar
  160. H. J. Do, T. Jin, J. H. Chung, J. W. Hwang, and M. J. Shin, “Voglibose administration regulates body weight and energy intake in high fat-induced obese mice,” Biochemical and Biophysical Research Communications, vol. 443, pp. 1110–1117, 2014. View at Google Scholar
  161. C. E. Koch, C. Lowe, D. Pretz, J. Steger, L. M. Williams, and A. Tups, “High fat diet induces leptin resistance,” Journal of Neuroendocrinology, vol. 28, no. 2, pp. 58–67, 2013. View at Google Scholar
  162. K. M. Gamber, L. Huo, S. Ha, J. E. Hairston, S. Greeley, and C. Bjørbæk, “Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity,” PLoS ONE, vol. 7, no. 1, Article ID e30485, 2012. View at Publisher · View at Google Scholar · View at Scopus
  163. C. Clemmensen, J. Chabenne, B. Finan et al., “GLP-1/glucagon co-agonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet,” Diabetes, vol. 63, no. 4, pp. 1422–1427, 2014. View at Google Scholar
  164. T. Roszer, T. Jozsa, E. D. Kiss-Toth, N. de Clerck, and L. Balogh, “Leptin receptor deficient diabetic (db/db) mice are compromised in postnatal bone regeneration,” Cell and Tissue Research, vol. 356, no. 1, pp. 195–206, 2013. View at Google Scholar
  165. R. Guzman-Ruiz, N. Gomez-Hurtado, M. Gil-Ortega et al., “Remodeling of energy metabolism and absence of electrophysiological changes in the heart of obese hyperleptinemic mice. New insights into the pleiotropic role of leptin,” Frontiers in Endocrinology, vol. 4, article 175, 2013. View at Google Scholar
  166. J. Benzler, Z. B. Andrews, C. Pracht et al., “Hypothalamic WNT signalling is impaired during obesity and reinstated by leptin treatment in male mice,” Endocrinology, vol. 154, pp. 4737–4745, 2013. View at Google Scholar
  167. L. Zabeau, F. Peelman, and J. Tavernier, “Antagonising leptin: current status and future directions,” Biological Chemistry, vol. 395, no. 5, pp. 499–514, 2014. View at Google Scholar
  168. P. D. Taylor, A. M. Samuelsson, and L. Poston, “Maternal obesity and the developmental programming of hypertension: a role for leptin,” Acta Physiologica, vol. 210, no. 3, pp. 508–523, 2014. View at Google Scholar
  169. M. D. Klok, S. Jakobsdottir, and M. L. Drent, “The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review,” Obesity Reviews, vol. 8, no. 1, pp. 21–34, 2007. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Grasman, “Reconstruction of the drive underlying food intake and its control by leptin and dieting,” PloS ONE, vol. 8, Article ID e74997, 2013. View at Google Scholar
  171. R. Muniyappa, R. J. Brown, A. Mari et al., “Effects of leptin replacement therapy on pancreatic beta-cell function in patients with lipodystrophy,” Diabetes Care, vol. 37, no. 4, pp. 1101–1107, 2014. View at Google Scholar
  172. R. Z. Tom, P. M. Garcia-Roves, R. J. Sjogren et al., “Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice,” Diabetes, vol. 63, no. 5, pp. 1560–1571, 2014. View at Publisher · View at Google Scholar
  173. N. Chapnik, Y. Genzer, A. Ben-Shimon, M. Y. Niv, and O. Froy, “AMPK-derived peptides reduce blood glucose but lead to fat retention in the liver of obese mice,” The Journal of Endocrinology, vol. 221, no. 1, pp. 89–99, 2014. View at Publisher · View at Google Scholar
  174. E. Tuduri, H. C. Denroche, J. A. Kara, A. Asadi, J. K. Fox, and T. J. Kieffer, “Partial ablation of leptin signaling in mouse pancreatic alpha-cells does not alter either glucose or lipid homeostasis,” American Journal of Physiology Endocrinology and Metabolism, vol. 306, no. 7, pp. E748–E755, 2014. View at Publisher · View at Google Scholar
  175. H. C. Denroche, J. Levi, R. D. Wideman et al., “Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling,” Diabetes, vol. 60, no. 5, pp. 1414–1423, 2011. View at Publisher · View at Google Scholar · View at Scopus
  176. J. P. A. Ioannidis, “Contradicted and initially stronger effects in highly cited clinical research,” Journal of the American Medical Association, vol. 294, no. 2, pp. 218–228, 2005. View at Publisher · View at Google Scholar · View at Scopus
  177. M. Wadman, “NIH mulls rules for validating key results,” Nature, vol. 500, pp. 14–16, 2013. View at Google Scholar
  178. K. K. Tsilidis, O. A. Panagiotou, E. S. Sena et al., “Evaluation of excess significance bias in animal studies of neurological diseases,” PLoS Biology, vol. 11, no. 7, Article ID e1001609, 2013. View at Publisher · View at Google Scholar · View at Scopus
  179. F. S. Collins and L. A. Tabak, “Policy: NIH plans to enhance reproducibility,” Nature, vol. 505, pp. 612–613, 2014. View at Google Scholar
  180. Y. Huang and R. Gottardo, “Comparability and reproducibility of biomedical data,” Briefings in Bioinformatics, vol. 14, pp. 391–401, 2013. View at Google Scholar
  181. J. Couzin-Frankel, “When mice mislead,” Science, vol. 342, pp. 922–925, 2013. View at Publisher · View at Google Scholar
  182. R. J. Traystman and P. S. Herson, “Misleading results: translational challenges,” Science, vol. 343, pp. 369–370, 2014. View at Google Scholar
  183. M. McNutt, “Reproducibility,” Science, vol. 343, no. 6168, article 229, 2014. View at Google Scholar
  184. M. Bissell, “Reproducibility: the risks of the replication drive,” Nature, vol. 503, pp. 333–334, 2013. View at Google Scholar
  185. J. P. A. Ioannidis, “Why most published research findings are false,” PLoS Medicine, vol. 2, no. 8, Article ID e124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  186. B. ] Alberts, M. W. Kirschner, S. Tilghman, and H. Varmus, “Rescuing US biomedical research from its systemic flaws,” Proceedings of the National Academy of Sciences, vol. 111, pp. 5773–5777, 2014. View at Google Scholar
  187. F. M. Marincola, “Translational medicine: a two-way road,” Journal of Translational Medicine, vol. 1, article 1, 2003. View at Publisher · View at Google Scholar · View at Scopus
  188. S. K. Chatterjee and M. L. Rohrbaugh, “NIH inventions translate into drugs and biologics with high public health impact,” Nature Biotechnology, vol. 32, pp. 52–58, 2014. View at Publisher · View at Google Scholar
  189. S. Khot, B. Soon Park, and W. T. Longstreth Jr., “The vietnam war and medical research: untold legacy of the U.S. doctor draft and the NIH “yellow berets”,” Academic Medicine, vol. 86, no. 4, pp. 502–508, 2011. View at Publisher · View at Google Scholar · View at Scopus
  190. M. M. Gottesman, “The role of the NIH in nurturing clinician-scientists,” The New England Journal of Medicine, vol. 368, no. 24, pp. 2249–2251, 2013. View at Publisher · View at Google Scholar · View at Scopus
  191. S. Broder, “Twenty-five years of translational medicine in antiretroviral therapy: promises to keep,” Science Translational Medicine, vol. 2, no. 39, p. 39ps33, 2010. View at Publisher · View at Google Scholar · View at Scopus
  192. K. Lewis, “Platforms for antibiotic discovery,” Nature Reviews Drug Discovery, vol. 12, no. 5, pp. 371–387, 2013. View at Publisher · View at Google Scholar · View at Scopus