Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

What is personalized medicine and what should it replace?

Nature Reviews Gastroenterology & Hepatology volume 9, pages 418–424 (2012)Cite this article

Subjects

Abstract

Personalized medicine is a new framework for medical care that involves modelling and simulation of a disease on the basis of its underlying mechanisms. This strategy must replace the 20th century paradigm of defining disease by pathology or associated signs and symptoms and conducting outcomes research that is based on the presence or absence of the disease syndrome. New technologies, including next-generation sequencing, the 'omics' and powerful computers provide massive amounts of accurate data. However, attempts to understand complex disorders by applying these new technologies within the 20th century framework have failed to produce the expected medical advances. To help physicians embrace a paradigm shift, the limitations of the old framework and major advantages of the new framework must be demonstrated. Chronic pancreatitis is an ideal complex disorder to study to consider the pros and cons of the two frameworks, because the pancreas is such a simple organ for disease modelling, and the advantages of personalized medicine are so profound.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Two approaches to assessing individual risk on the basis of the presence or absence of six variables, using risk of a major cardiovascular event as an example.
Figure 2: Clinical pathway of patients being evaluated for suspected pancreatic disease used at the University of Pittsburgh.

Similar content being viewed by others

References

  1. Kuhn, T. S. The Structure of Scientific Revolutions 1st edn (University of Chicago, Chicago, 1962).

    Google Scholar 

  2. Committee on a Framework for Development a New Taxonomy of Disease; National Research Council. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease. (National Academies Press, Washington, DC, 2011).

  3. Whitcomb, D. C. Going MAD: development of a “matrix academic division” to facilitate translating research to personalized medicine. Acad. Med. 86, 1353–1359 (2011).

    Article  Google Scholar 

  4. Flexner, A. Medical education in the United States and Canada: A report to the Carnegie Foundation for the advancement of teaching (Boston, Mass, 1910).

    Google Scholar 

  5. Etemad, B. & Whitcomb, D. C. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 120, 682–707 (2001).

    Article  CAS  Google Scholar 

  6. Steer, M. L., Waxman, I. & Freedman, S. Chronic pancreatitis. N. Engl. J. Med. 332, 1482–1490 (1995).

    Article  CAS  Google Scholar 

  7. Pao, W. & Girard, N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12, 175–180 (2011).

    Article  CAS  Google Scholar 

  8. Russnes, H. G., Navin, N., Hicks, J. & Borresen-Dale, A. L. Insight into the heterogeneity of breast cancer through next-generation sequencing. J. Clin. Invest. 121, 3810–3818 (2011).

    Article  CAS  Google Scholar 

  9. Friess, H. et al. Identification of disease-specific genes in chronic pancreatitis using DNA array technology. Ann. Surg. 234, 769–778 (2001).

    Article  CAS  Google Scholar 

  10. Shrikhande, S. V. et al. Comparison of histological features and inflammatory cell reaction in alcoholic, idiopathic and tropical chronic pancreatitis. Br. J. Surg. 90, 1565–1572 (2003).

    Article  CAS  Google Scholar 

  11. Whitcomb, D. C. Mechanisms of disease: Advances in understanding the mechanisms leading to chronic pancreatitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 1, 46–52 (2004).

    Article  Google Scholar 

  12. Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA 268, 2420–2425 (1992).

  13. Wyer, P. C. & Silva, S. A. Where is the wisdom? A conceptual history of evidence-based medicine. J. Eval. Clin. Pract. 15, 891–898 (2009).

    Article  Google Scholar 

  14. Krishna, R. Model-based benefit-risk assessment: can Archimedes help? Clin. Pharmacol. Ther. 85, 239–240 (2009).

    Article  CAS  Google Scholar 

  15. Eddy, D. M. et al. Individualized guidelines: the potential for increasing quality and reducing costs. Ann. Intern. Med. 154, 627–634 (2011).

    Article  Google Scholar 

  16. Witte, J. S. Genome-wide association studies and beyond. Annu. Rev. Public Health 31, 9–20 (2010).

    Article  Google Scholar 

  17. Anderson, C. A. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43, 246–252 (2011).

    Article  CAS  Google Scholar 

  18. Franke, A. et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42, 1118–1125 (2010).

    Article  CAS  Google Scholar 

  19. Wheeler, E. & Barroso, I. Genome-wide association studies and type 2 diabetes. Brief. Funct. Genomics 10, 52–60 (2011).

    Article  CAS  Google Scholar 

  20. Voight, B. F. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579–589 (2010).

    Article  CAS  Google Scholar 

  21. DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat. Genet. 43, 491–498 (2011).

    Article  CAS  Google Scholar 

  22. McKernan, K. J. et al. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res. 19, 1527–1541 (2009).

    Article  CAS  Google Scholar 

  23. Whitcomb, D. C. & Ermentrout, G. B. A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice. Pancreas 29, E30–E40 (2004).

    Article  Google Scholar 

  24. Park, H. W. et al. Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139, 620–631 (2010).

    Article  CAS  Google Scholar 

  25. Schneider, A. et al. combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis. Gastroenterology 140, 162–171 (2011).

    Article  CAS  Google Scholar 

  26. Chen, J. M. & Férec, C. Chronic pancreatitis: genetics and pathogenesis. Annu. Rev. Genomics Hum. Genet. 10, 63–87 (2009).

    Article  CAS  Google Scholar 

  27. Whitcomb, D. C. Genetic aspects of pancreatitis. Annu. Rev. Med. 61, 413–424 (2010).

    Article  CAS  Google Scholar 

  28. Yadav, D. et al. Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch. Intern. Med. 169, 1035–1045 (2009).

    Article  Google Scholar 

  29. Whitcomb, D. C. Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut 45, 317–322 (1999).

    Article  CAS  Google Scholar 

  30. Yadav, D. & Whitcomb, D. C. The role of alcohol and smoking in pancreatitis. Nat. Rev. Gastroenterol. Hepatol. 7, 131–145 (2010).

    Article  Google Scholar 

  31. Deng, X. et al. Chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in rats. Am. J. Pathol. 166, 93–106 (2005).

    Article  CAS  Google Scholar 

  32. Nordback, I. et al. The recurrence of acute alcohol-associated pancreatitis can be reduced: a randomized controlled trial. Gastroenterology 136, 848–855 (2009).

    Article  Google Scholar 

  33. Talamini, G. et al. Smoking cessation at the clinical onset of chronic pancreatitis and risk of pancreatic calcifications. Pancreas 35, 320–326 (2007).

    Article  Google Scholar 

  34. Van Goor, F. et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc. Natl Acad. Sci. USA 108, 18843–18848 (2011).

    Article  CAS  Google Scholar 

  35. Morinville, V. D., Lowe, M. E., Elinoff, B. D. & Whitcomb, D. C. Hereditary pancreatitis amlodipine trial: a pilot study of a calcium-channel blocker in hereditary pancreatitis. Pancreas 35, 308–312 (2007).

    Article  CAS  Google Scholar 

  36. Shimosegawa, T. et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 40, 352–358 (2011).

    Article  Google Scholar 

  37. Mullady, D. K. et al. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut 60, 77–84 (2011).

    Article  Google Scholar 

  38. Clarke, B. et al. Endoscopic therapy is effective for patients with chronic pancreatitis. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/j.cgh.2011.12.040.

  39. Sutton, J. M. et al. Total pancreatectomy and islet cell autotransplantation as a means of treating patients with genetically linked pancreatitis. Surgery 148, 676–685 (2010).

    Article  Google Scholar 

  40. Bellin, M. D. et al. Quality of life improves for pediatric patients after total pancreatectomy and islet autotransplant for chronic pancreatitis. Clin. Gastroenterol. Hepatol. 9, 793–799 (2011).

    Article  Google Scholar 

  41. LaRusch, J., Barmada, M. M., Solomon, S. & Whitcomb, D. C. Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred. JOP 13, 258–262 (2012).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The author thanks the following people for critical review of the manuscript and helpful discussion: Michelle Kienholz, Christopher Langmead PhD, Mark S. Roberts MD MMP and Adam Slivka MD PhD. Work from the author's group discussed in this publication was supported by the following: National Institutes of Health (NIH) DK054709, DK061451, DK077906, the University of Pittsburgh Genomics and Proteomics Core Laboratory and the National Center for Research Resources (NCRR), a component of the NIH Roadmap for Medical Research (UL1 RR024153), the UPCI Clinical Genomics Immunoproteomics and Sequencing Facility (NIH P30CA047904), The Frieda G. and Saul F. Shapira BRCA Cancer Research Program and the Wayne Fusaro Pancreatic Cancer Research Fund (DCW).

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Department of Cell Biology & Molecular Physiology, Hepatology and Nutrition, and Human Genetics, University of Pittsburgh, Medical Arts Building, 3708 Fifth Avenue, Suite 401.5, Pittsburgh, 15213, PA, USA

    David C. Whitcomb

Authors
  1. David C. Whitcomb
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

D. C. Whitcomb owns stocks in Ambry Genetics and also the US patent 6406846 entitled “Method for determining whether a human patient is susceptible to hereditary pancreatitis, and primers therefore”, which has been licensed and provides royalty income.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Whitcomb, D. What is personalized medicine and what should it replace?. Nat Rev Gastroenterol Hepatol 9, 418–424 (2012). https://doi.org/10.1038/nrgastro.2012.100

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2012.100

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing