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.

  • Science and Society
  • Published:

Integrating pharmacogenetics into society: in search of a model

Nature Reviews Genetics volume 5, pages 663–669 (2004)Cite this article

Abstract

There has been considerable scientific, corporate and policy interest in the more effective use of genetics in both drug development and delivery. Pharmacogenetics — the study of the relationship between an individual's genetic makeup and response to medicinal drugs — has attracted global interest, but will it live up to its promise? Looking beyond the hype that has accompanied much of the commentary in the area, the future of pharmacogenetics will depend on how competing interests and options are resolved.

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

Relevant articles

Open Access articles citing this article.

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: Commercial collaborations based on pharmacogenetics.
Figure 2: Collaborative links and strategic options for the use of pharmacogenetics (PGx).

References

  1. Smart, A. & Martin, P. The promise of personalised medicine? Assessing the prospects for disease and patient stratification. Stud. Hist. Philos. Biol. Biomed. Sci. (in the press).

  2. Department of Health. Our Inheritance, Our Future – Realising the Potential of Genetics in the NHS (The Stationary Office, London, 2003).

  3. Frantz, S. & Smith, A. New drug approvals for 2002. Nature Rev. Drug Discov. 2, 95–96 (2003)

    Article  CAS  Google Scholar 

  4. Brazell, C., Freeman, A. & Mosteller, M. Maximizing the value of medicines by including pharmacogenetic research in drug development and surveillance. Br. J. Clin. Pharmacol. 53, 224–231 (2002).

    Article  CAS  Google Scholar 

  5. Food and Drug Administration. Glaxo Wellcome Decide to Withdraw Lotronex from the Market. <http://www.fda.gov/bbs/topics/answers/ANS01058.html> (Office of Public Affairs, Washington, 2000).

  6. Food and Drug Administration. FDA Approves restricted marketing of Lotronex. <http://www.fda.gov/bbs/topics/NEWS/2002/NEW00814.html> (Department of Health and Human Services, Washington, 2002).

  7. Houn, F. Letter, NDA-21-107/S-005, Office of Drug Evaluation II, Centre for Drug Evaluation and Research <http://www.fda.gov/cder/foi/appletter/2002/21107s5ltr.pdf> (Food and Drug Administration to GlaxoSmithKline, 2002).

  8. Goldstein, D. B. Pharmacogenetics in the laboratory and the clinic. N. Engl. J. Med. 348, 553–556 (2003).

    Article  Google Scholar 

  9. Holtzman, N. A. in Pharmacogenomics: Social, Ethical, and Clinical Dimensions (ed. Rothstein, M. A.) 163–186 (Wiley-Liss, Hoboken, New Jersey, 2003).

    Book  Google Scholar 

  10. Omenn, G. & Motulsky, A. in Pharmacogenomics: Social, Ethical, and Clinical Dimensions (ed. Rothstein, M. A.) 137–162 (Wiley-Liss, Hoboken, New Jersey, 2003).

    Google Scholar 

  11. Nuffield Council of Bioethics. Pharmacogenetics: Ethical Issues (Nuffield Council of Bioethics, London, 2003).

  12. Melzer, D. et al. My Very Own Medicine: What Must I Know? <http://www.phpc.cam.ac.uk/epg/Report.pdf> (Department of Public Health and Primary Care, Univ. Cambridge, Cambridge, 2003).

    Google Scholar 

  13. Lindpaintner, K. Pharmacogenetics and the future of medical practice. Br. J. Clin. Pharmacol. 54, 221–230 (2002).

    Article  Google Scholar 

  14. Pirmohamed, M. & Park, B. K. Genetic susceptibility to adverse drug reactions. Trends Pharmacol. Sci. 22, 298–305 (2001).

    Article  CAS  Google Scholar 

  15. Roses, A. Pharmacogenetics and the practice of medicine Nature, 405, 857–865 (2000).

    Article  CAS  Google Scholar 

  16. Clozapine Summary Sheet SS95/09 <www.keele.ac.uk/depts/mm/MTRAC/ProductInfo/summaries/ C/CLOZAPINEs.html> (MTRAC, Department of Medicines Management, Keele Univ, Keele, 1995)

  17. Arranz, M. J. et al. Pharmacogenetic prediction of clozapine response. Lancet 355, 1615–1616 (2000).

    Article  CAS  Google Scholar 

  18. Mancama, D., Arranz, M. J. & Kerwin, R. W. Genetic predictors of therapeutic response to clozapine: current status of research. CNS Drugs 16, 317–324 (2002).

    Article  CAS  Google Scholar 

  19. Holtzman, N. A. & Watson, M. S. (eds) Promoting Safe and Effective Genetic Testing in the United States. Final Report. (Johns Hopkins Univ. Press, Baltimore, Maryland, 1998).

    Google Scholar 

  20. Robertson, J. A., Brody, B., Buchannan, A., Kahn, J. & McPherson, E. Pharmacogenetic challenges for the health care system. Health Aff. 21, 155–167 (2002).

    Article  Google Scholar 

  21. Rothstein, M. A. & Epps, P. G. Ethical and legal implications of pharmacogenomics. Nature Rev. Genet. 2, 228–231 (2001).

    Article  CAS  Google Scholar 

  22. Issa, A. M. Ethical perspectives on pharmacogenomic profiling in the drug development process. Nature Rev. Drug Discov. 1, 300–308 (2002).

    Article  CAS  Google Scholar 

  23. Smart, A., Parker, M. & Martin, P. Tailored medicine: who will it fit? The ethics of patient and disease stratification. Bioethics (in the press).

  24. Pirmohamed, M & Lewis, G. in Regulating Pharmaceuticals in Europe: Striving For Efficiency, Equity and Quality (eds Mossialos, E., Mrazek, M. & Walley, T.) 279–296 (Open Univer. Press, Maidenhead, 2004).

    Google Scholar 

  25. Stearns, V., Davidson, N. E. & Flockhart, D. Pharmacogenetics in the treatment of breast cancer. Pharmacogenetics 4, 143–153 (2004).

    Article  CAS  Google Scholar 

  26. Marsh, S. & McLeod, H. Cancer pharmacogenetics. Brit. J. Cancer 90, 8–11 (2004).

    Article  CAS  Google Scholar 

  27. Department of Health and Human Services. Draft guidance for industry: pharmacogenomic data submissions <http://www.fda.gov/OHRMS/DOCKETS/98fr/03d-0497-nad0001vol1.pdf> (Food and Drug Administration, 2003).

  28. Savage, D. R. FDA guidance on pharmacogenomics data submission. Nature Rev. Drug Discov. 2, 937–938 (2003).

    Article  Google Scholar 

  29. The European Agency for the Evaluation of Medicinal Products. Concept paper on pharmacogenetics — briefing matters. CPMP/4445/03 <http://www.emea.eu.int/pdfs/human/pharmacogenetics/444503en.pdf> (The European Agency for the Evaluation of Medicinal Products, 23 Jan 2003).

  30. Lesko, L. J. & Woodcock, J. Pharmacogenomic-guided drug development: regulatory perspective. Pharmacogenomics J. 2, 20–24 (2002).

    Article  CAS  Google Scholar 

  31. Ratner, M. L. Pharmacogenomic data and labeling: a less-safe harbor for existing drugs? Windhover's Update <http://www/windhover.com/update/05252003/2003800094> (2003).

  32. Anonymous. FDA's Lesko says pharmacogenomics guidance paper due mid-year. Pharmacogenomics Reporter (New York) 6 (17 Jan 2003).

  33. Abraham, J. & Lewis, G. Regulating Medicines in Europe (Routledge, London, 2000).

    Google Scholar 

  34. European Commission. The in vitro diagnostic medical devices directive (98/79/EC). Official J. Eur. Communities L331/1 (27 Oct 1998).

  35. Danzon, P. & Towse, A. The economics of gene therapy and of pharmacogenetics. Value Health 5, 5–13 (2002).

    Article  Google Scholar 

  36. Audit Commission. A spoonful of medicine: medicines management in NHS hospitals. <http://www.audit-commission.gov.uk/Products/NATIONAL-REPORT/E83C8921-6CEA-4b2c-83E7-F80954A80F85/nrspoonfulsugar.pdf> (Audit Commission, London, 2001).

Download references

Acknowledgements

This research on which this paper is based was supported by a Wellcome Trust grant titled 'The clinical and commercial development of Pharmacogenetics'.

Author information

Authors and Affiliations

  1. Science and Technology Studies Unit, University of York, York, YO10 5DD, United Kingdom

    Andrew Webster & Graham Lewis

  2. Institute for Study of Genetics, Biorisks and Society, University of Nottingham, Nottingham, NG7 2RD, United Kingdom

    Paul Martin

  3. Oxford Genetics Knowledge Park, University of Oxford, Oxford, OX3 7LF, United Kingdom

    Andrew Smart

Authors
  1. Andrew Webster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graham Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew Smart
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Encyclopedia of Life Sciences

pharmacogenetics

Institute for the Study of Genetics, Biorisks and Society

Lewis' homepage

Oxford Genetics Knowledge Park

Pharmacogenetics research at SATSU

University of York Science and Technology Studies Unit

Webster's homepage

Glossary

ABACAVIR

An antiviral drug, used, in conjunction with other medicines, for the treatment of HIV.

AGRANULOCYTOSIS

A condition in which there is an insufficient number of white blood cells called neutrophils or granulocytes. This can be caused by a failure of the bone marrow to make sufficient neutrophils or when white blood cells are destroyed faster than they can be produced. Affected people are susceptible to infections.

BIOBANKS

Public or private tissue collections (derived from blood, DNA or other sources) comprising samples taken from specific disease groups or healthy populations. Their long-term purpose is to build biological banks that will provide new sources of (genetic) information about disease that have clinical value.

CLOZAPINE

An antipsychotic drug that works by decreasing abnormal excitement in the brain, used primarily to treat patients with schizophrenia who either fail to respond to or are unable to take other antipsychotic treatments.

DISPOSITION

Refers to all processes involved in the absorption, distribution metabolism and excretion of drugs in a living organism.

INVESTIGATIONAL NEW DRUG APPLICATION

(IND). An application that a drug sponsor must submit to FDA before beginning tests of a new drug on humans. The IND contains the plan for the study and is supposed to give a complete picture of the drug, including its structural formula, animal test results, and manufacturing information.

ISONIAZID

An antibacterial drug used to treat tuberculosis.

NEW DRUG APPLICATION

An application requesting FDA approval to market a new drug for human use in interstate commerce. The application must contain, among other things, data from specific technical viewpoints for FDA review — including chemistry, pharmacology, medical, biopharmaceutics, statistics and, for anti-infectives, microbiology.

PHARMACODYNAMIC CHARACTERISTICS

The characteristics of a drug that determine its biochemical and physiological effects and its mechanisms of action.

PHARMACOVIGILANCE

The process of monitoring medicines to identify previously unrecognised adverse effects; assessing the risks and benefits of medicines in order to determine what action, information and subsequent monitoring, if any, is necessary to improve their safe use.

THERAPEUTIC INDEX

The therapeutic index of a drug is the ratio of the toxic dose to the therapeutic (that is, effective) dose, often used as a measure of the relative safety of the drug for a particular treatment. PGx is more likely to be clinically useful where the therapeutic index is narrow (i.e. when there is a smaller amount of difference between toxic and efficacious doses).

'RESTRICTED MARKETING' TERMS

A drug may have such serious adverse effects that regulatory approval is given for use in a specific patient group only, for whom it can be used safely.

THIOPURINES

A family of chemotherapeutics used to treat leukaemia, as well as arthritis and inflammatory bowel disease.

WARFARIN

Used to prevent blood clots from forming or growing larger (anticoagulant). Typically used for patients with atrial fibrillation and those with a venous thromboembolism.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Webster, A., Martin, P., Lewis, G. et al. Integrating pharmacogenetics into society: in search of a model. Nat Rev Genet 5, 663–669 (2004). https://doi.org/10.1038/nrg1430

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1430

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