Skip to main content
SpringerLink
Log in

Power, expertise and the limits of representative democracy: genetics as scientific progress or political legitimation in carcinogenic risk assessment of pharmaceuticals?

  • Original Article
  • Published:
Journal of Community Genetics Aims and scope Submit manuscript

Abstract

In modern ‘representative’ democratic states, the legitimacy of governments’ actions rests on their publicly declared commitment to protect the interests of their citizens. Regarding the pharmaceutical sector in most democracies, new drug products are developed and marketed by a capitalist industry, whose member firms, via shareholders, have commercial interests in expanding product sales. In those democracies, states have established government agencies to regulate the pharmaceutical industry on behalf of citizens. State legislatures, such as the US Congress and European Parliaments, have charged government drug regulatory agencies with the legal responsibility to protect public health. Yet, this paper argues that government drug regulatory agencies in the EU, Japan, and USA have permitted the pharmaceutical industry to reshape the regulatory guidance for carcinogenic risk assessment of pharmaceuticals in ways that are not techno-scientifically defensible as bases for improved, or even equivalent, protection of public health, compared with the previous techno-regulatory standards. By adopting the industry’s agenda of streamlining carcinogenicity testing in order to accelerate drug development and regulatory review, it is contended that these regulatory agencies have allowed the techno-regulatory standards for carcinogenic risk assessment to be loosened in ways that are presented as scientific progress resulting from new genetics, but for which there is little evidence of progress in public health protection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Notes

  1. Some scientists refer to these life span carcinogenicity studies as ‘long-term’, rather than ‘life span’, but we regard that as less illuminating for the reader.

  2. In this context, a positive carcinogenicity finding refers to an experimental result implying that the pharmaceutical compound in question induced tumours and/or cancer in the test animal (mouse/rat), while negative findings refer to results implying no such cancer induction.

  3. The data reviews from the Japanese Pharmaceutical Manufacturers Association and the UK industry-funded Centre for Medicines Research related only to industry knowledge of drug development before full regulatory review. Consequently, no analysis of that data independent of industry had been conducted, which raises fundamental methodological limitations. For that reason, most of our discussion concerns the databases and regulatory positions analysed by the European regulators and the FDA.

  4. We would suggest that 40 per cent could equally be regarded as quite a high percentage, and that ICH’s interpretation of it as low was arbitrary.

  5. Interviews with: Vice President of Clinical Safety, Janssen; Vice President of Drug Safety, Millenium Pharmaceuticals; highly distinguished industry toxicologist involved with ILSI.

  6. Some argued that the short-term in vivo genetically engineered animal models might provide additional information on genotoxicity when a compound’s genotoxicity was equivocal from in vitro tests (van der Laan and Spindler 2002).

  7. Interview with ‘representative’ of the UK Department of Health’s Committee on Carcinogenicity.

  8. Interview with Vice-President of Clinical Safety, Janssen Pharmaceuticals.

  9. Interviews with Managing Director of Safety Assessment, Astra Charnwood; senior UK industry toxicologist.

  10. Interview with Director of Toxicology, Pharmacia & Upjohn.

  11. Interview with Vice-President of Regulatory Affairs, Hoechst Marion Roussel.

  12. Interview with ‘representative’ of the UK Medicines Control Agency, now known as the Medicines and Healthcare Products Regulatory Agency.

  13. Interview with Astra Zeneca toxicologist involved with the ABPI.

  14. Interviews with former UK academic Professor of Toxicology involved with ILSI; Highly Distinguished Industry Toxicologist involved with ILSI.

  15. Interview with Former Associate Director of Toxicology and Pharmacology at FDA.

  16. Interviews with Vice-President of Safety Assessment, Novartis; Government scientist leading Transgenic Carcinogenesis Group at Laboratory of Molecular Toxicology at the US National Institute of Environmental Sciences; Dutch scientist at the Laboratory of Toxicology, Pathology and Genetics at the Netherlands National Institute of Public Health and Environment; Director of National Center for Tocicogenomics at the US National Institute of Environmental Sciences.

  17. Interview with Industry scientist involved with ILSI ACT.

  18. Interview with academic scientist and former member of the UK Committee on Carcinogenicity.

  19. Interview with senior UK industry toxicologist.

References

  • Abraham J (1995) Science, politics and the pharmaceutical industry. UCL/St Martin’s Press, London/New York

    Google Scholar 

  • Abraham J (1998) Regulating the cancer-inducing potential of non-steroidal anti-inflammatory drugs: some lessons from the 1970s and 1980s. Soc Sci Med 46:39–51

    Article  PubMed  CAS  Google Scholar 

  • Abraham J, Lewis G (2000) Regulating medicines in Europe. Routledge, London

    Google Scholar 

  • Abraham J, Reed T (2001) Trading risks for markets: the international harmonisation of pharmaceuticals regulation. Health Risk Soc 3:113–128

    Google Scholar 

  • Anon (1992) ICH progress so far. Scrip 1707:14–15

    Google Scholar 

  • Ashby J (1996) Alternatives to the 2-species bioassay for the identification of potential human carcinogens. Hum Exp Toxicol 15:183–202

    Article  PubMed  CAS  Google Scholar 

  • Ashby J, Tennant RW (1991) Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the US National Toxicology Programme. Mutat Res 257:229–306

    PubMed  CAS  Google Scholar 

  • Bentley P, Baier H, Krug E (1992) Results from carcinogenicity tests in two rodent species - do they improve or confuse decision-making? An industry viewpoint. In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 111–120

    Google Scholar 

  • Centre for Medicines Research (CMR) (1995) Annual report for 1995. CMR, Carshalton, Surrey

    Google Scholar 

  • CoC (2003) Statement on ILSI/HESI research programme on alternative cancer models. Toxicol Pathol 31:254–257

    Google Scholar 

  • Cohen SM, Robinson D, MacDonlad JS (2001) Alternative models for carcinogenicity testing. Toxicol Sci 64:14–19

    Article  PubMed  CAS  Google Scholar 

  • Contrera JF (1996) FDA science symposium: developing alternative in vivo approaches for the assessment of carcinogenicity: background and objectives. Toxicol Pathol 24:514

    Article  Google Scholar 

  • Contrera JF, Jacobs AC, DeGeorge JJ (1997) Carcinogenicity testing and the evaluation of regulatory requirements for pharmaceuticals. Regul Toxicol Pharmacol 25:130–145

    Article  PubMed  CAS  Google Scholar 

  • Cordaro JC (1989) Transgenic mice as future tools in risk assessment. Risk Anal 9:157–168

    Article  PubMed  CAS  Google Scholar 

  • D’Arcy PF, Harron DWG (eds) (1996) Proceedings of the third international conference on harmonisation. Queen’s University Belfast, Belfast

    Google Scholar 

  • DeGeorge J (1996) A regulatory perspective of the guidance on the utility of two rodent species. In: D’Arcy PF, Harron DWG (eds) Proceedings of the third international conference on harmonisation. Queen’s University Belfast, Belfast, pp 274–277

    Google Scholar 

  • Department of Health (1997) Annual Report of the Committee on Toxicity, Mutagenicity, and Carcinogenicity of Chemicals in Food, Consumer Products and the Environment

  • Easlea B (1973) Liberation and the aims of science. Scottish Academic Press, Edinburgh

    Google Scholar 

  • Eastin WC, Mennear JH, Tennant RW, Stoll RE, Branstetter GE, Bucher JR, McCullough B, Binder RL, Spalding JW, Mahier JF (2001) TgAC genetically altered mouse: assay working group overview of available data. Toxicol Pathol 29(suppl):60–80

    Article  PubMed  CAS  Google Scholar 

  • Ekman L (1996) Panel discussion. In: D’Arcy PF, Harron DWG (eds) Proceedings of the third international conference on harmonisation. Queen’s University Belfast, Belfast, pp 295–302

    Google Scholar 

  • Emmerson JL (1992) High dose selection in the design of studies to evaluate the carcinogenic potential of pharmaceutical: industry perspectives. In: D’Arcy PF, Harron DWG (eds) Proceedings of the first international conference on harmonisation. Queen’s University Belfast, Belfast, pp 202–208

    Google Scholar 

  • Fung VA, Barrett JC, Huff J (1995) The carcinogenesis bioassay in perspective: application in identifying human cancer hazards. Environ Heal Perspect 103:680–683

    CAS  Google Scholar 

  • GeneWatch (2002) Genetically modified and cloned animals. All in a good cause? GeneWatch, London

    Google Scholar 

  • Goodman JI (2001) A perspective on current and future uses of alternative models for carcinogenicity testing. Toxicol Pathol 29:173–176

    Article  PubMed  CAS  Google Scholar 

  • Halliday RG, Drasdo AL, Lumley CE, Walker SR (1997) The allocation of resources for R & D in the world’s leading pharmaceutical companies. R & D Manag 27:63–77

    Article  Google Scholar 

  • Hayashi Y (1994) Utility of two rodent species: current regulatory perspectives. In: D’Arcy PF, Harron DWG (eds) Proceedings of the second international conference on harmonisation. Queen’s University Belfast, Belfast, pp 291–293

    Google Scholar 

  • IFPMA (2000) The value and benefits of ICH to industry. IFPMA, Geneva

    Google Scholar 

  • King RJB (1996) Cancer biology. Longman, Harlow, Essex

    Google Scholar 

  • Laws D, Rein M (2003) Reframing practice. In: Hajer MA, Wagenaar H (eds) Deliberative policy analysis: understanding governance in the network society. Cambridge University Press, Cambridge, pp 172–206

    Chapter  Google Scholar 

  • Lumley CE, Van Cauteren H (1997) Harmonisation of international toxicity testing guidelines for pharmaceuticals: contribution to refinement and reduction in animal use. European Biological Research Association Bulletin, November (reprinted)

  • MacDonald JS (1998) Evaluation of mew models II. In: D’Arcy PF, Harron DWG (eds) Proceedings of the fourth international conference on harmonisation. Queen’s University Belfast, Belfast, pp 272–277

    Google Scholar 

  • Mitsumori K (1998) Evaluation of new models I: initiation and promotion models and the Hras 2 mouse model. In: D’Arcy PF, Harron DWG (eds) Proceedings of the fourth international conference on harmonisation. Queen’s University Belfast, Belfast, pp 263–271

    Google Scholar 

  • Monro A (1992) Why do chemicals apparently cause tumours more readily in rodents than in humans: biology or exposure? In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 25–44

    Google Scholar 

  • Monro AM (1994) Utility of two rodent species: some arguments for and against. In: D’Arcy PF, Harron DWG (eds) Proceedings of the second international conference on harmonisation. Queen’s University Belfast, Belfast, pp 293–300

    Google Scholar 

  • Monro A (1996) Testing for carcinogenic potential: Rapporteur’s report. In: D’Arcy PF, Harron DWG (eds) Proceedings of the third international conference on harmonisation. Queen’s University Belfast, Belfast, pp 260–268

    Google Scholar 

  • Mulliger B (1997) Science should drive regulatory decisions, advise carcinogenicity workshop participants. CMR News 16(Spring):16–19

    Google Scholar 

  • Parkinson C, Grasso P (1993) The use of the dog in toxicity tests on pharmaceutical compounds. Hum Exp Toxicol 12:99–109

    Article  PubMed  CAS  Google Scholar 

  • Pettit SD (2001) Panel discussion on the application of alternative models to cancer risk assessment. Toxicol Pathol 29:191–195

    Article  PubMed  Google Scholar 

  • Purchase I (1992) Current knowledge of mechanisms of carcinogenicity: genotoxins versus non-genotoxins. In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 3–24

    Google Scholar 

  • Roe F (1992) Factors affecting the duration of carcinogenicity studies: when should they end? In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 103–109

    Google Scholar 

  • Scales D, Griffin J (1992) Use of two matched strains: can they improve sensitivty? In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 129–139

    Google Scholar 

  • Schou JS (1992) Predictive value of carcinogenicity studies for drug safety. In: D’Arcy PF, Harron DWG (eds) Proceedings of the first international conference on harmonisation. Queens University Belfast, Belfast, pp 208–212

    Google Scholar 

  • Schumpeter J (1942) Capitalism, socialism and democracy. Harper & Row, New York

    Google Scholar 

  • Sistare FD, Thompson KL, Honchel R, DeGeorge JJ (2002) Evaluation of the TgAC transgenic mouse assay for testing the human carcinogenic potential of pharmaceuticals—practical pointers, mechanistic clues, and new questions. Int J Toxicol 21:65–79

    Article  PubMed  CAS  Google Scholar 

  • Storer R, French JE, Haseman JK, Hajian G, LeGrand EK, Long GG, Mixson LA, Ochoa R (2001) P53 hemizygous knock-out mouse: overview of available data. Toxicol Pathol 29(suppl):30–50

    Article  PubMed  CAS  Google Scholar 

  • Tennant RW (1996) FDA science symposium: developing alternative in vivo approaches for the assessment of carcinogenicity. Toxicol Pathol 25:516

    Google Scholar 

  • Tennant RW, French JE, Spalding JW (1995) Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models. Environ Heal Perspect 103:942–950

    Article  CAS  Google Scholar 

  • Usui T, Griffiths SA, Lumley CE (1996) Industry viewpoint: the utility of the mouse for the assessment of the carcinogenic potential of pharmaceuticals. In: D’Arcy PF, Harron DWG (eds) Proceedings of the third international conference on harmonisation. Queen’s University Belfast, Belfast, pp 279–284

    Google Scholar 

  • Usui T, Mutai M, Hisada S, Takoaka M, Soper KA, McCullough B, Alden C (2001) CB6F1-rasH2 mouse: overview of available data. Toxicol Pathol 29(suppl):90–108

    Article  PubMed  CAS  Google Scholar 

  • Van der Laan JW, Spindler P (2002) The in vivo rodent test systems for assessment of carcinogenic potential. Regul Toxicol Pharmacol 35:122–125

    Article  PubMed  Google Scholar 

  • Van Kreijl CF, McAnulty PA, Beems RB, Vynckier A, van Steeg H, Fransson-Steen R, Alden C, Forster R, van der Laan JW, Vandenberghe J (2001) Xpa and Xpa/p53 knock-out mice: overview of available data. Toxicol Pathol 29(suppl):117–127

    Article  PubMed  Google Scholar 

  • Van Oosterhout JPJ, Van der Laan JW, Waal EJ, Olejniczak K, Hilgenfeld M, Schmidt V, Bass R (1997) The utility of two rodent species in carcinogenic risk assessment of pharmaceuticals in Europe. Regul Toxicol Pharmacol 25:6–17

    Article  PubMed  Google Scholar 

  • Weissinger J (1992) Factors affecting the duration of carcinogenicity studies: when should a study end?—A regulatory viewpoint. In: McAuslane JAN, Lumley CE, Walker SR (eds) The carcinogenicity debate. Quay Publishing, Carshalton, Surrey, pp 73–76

    Google Scholar 

  • WHO (1969) Principles for the testing and evaluation of drugs for carcinogenicity. WHO, Geneva, p 426, Technical Report Series

    Google Scholar 

  • Zbinden G (1987) Risk predicted from animal studies. In: Walker SR, Asscher WA (eds) Medicines and risk/benefit decisions. MTP Press, Lancaster, pp 49–56

    Chapter  Google Scholar 

Download references

Acknowledgments

We are grateful to the Wellcome Trust for funding some of the research on which this paper is based and to two anonymous referees for their comments on a previous draft. Thanks also to the University of Lund ‘Genetics and Democracy’ seminar series to which some aspects of this paper were previously presented.

Author information

Authors and Affiliations

  1. Centre for Research and Health in Medicine (CRHaM), Department of Sociology, University of Sussex, Sussex, UK

    John Abraham

  2. Cancer Research UK, Psychosocial Oncology Group, Brighton and Sussex Medical School, University of Sussex, Sussex, UK

    Rachel Ballinger

Authors
  1. John Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel Ballinger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Abraham.

Additional information

Special Issue: Genetics and Demogracy

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abraham, J., Ballinger, R. Power, expertise and the limits of representative democracy: genetics as scientific progress or political legitimation in carcinogenic risk assessment of pharmaceuticals?. J Community Genet 3, 91–103 (2012). https://doi.org/10.1007/s12687-011-0060-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12687-011-0060-2

Keywords

Search

Navigation