Skip to main content

Thank you for visiting 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.

  • Letter
  • Published:

Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent


There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or ‘prion’ diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains1,2,3,4. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species5,6,7. This BSE ‘signature’ has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant6,8, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt–Jakob disease (CJD), referred to as ‘new variant’ CJD (vCJD)9, have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France10. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

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

Access options

Buy this article

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

Figure 1: Incubation times in mice with spongiform encephalopathies.
Figure 2: Lesion profiles for mice following transmission of spongiform encephalopathies.
Figure 3: Survival curves for mice following transmission of spongiform encephalopathies.

Similar content being viewed by others


  1. Dickinson, A. G. & Meikle, V. M. H. Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol. Gen. Genet. 112, 73–79 (1971).

    Article  CAS  Google Scholar 

  2. Fraser, H. & Dickinson, A. G. Scrapie in mice: agent-strain differences in the distribution and intensity of grey matter vacuolation. J. Comp. Pathol. 83, 29–40 (1973).

    Article  CAS  Google Scholar 

  3. Bruce, M. E., McConnell, I., Fraser, H. & Dickinson, A. G. The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. J. Gen. Virol. 72, 595–603 (1991).

    Article  CAS  Google Scholar 

  4. Bruce, M. E. Scrapie strain variation and mutation. Br. Med. Bull. 49, 822–838 (1993).

    Article  CAS  Google Scholar 

  5. Fraser, H., Bruce, M. E., Chree, A., McConnell, I. & Wells, G. A. Transmission of bovine spongiform encephalopathy and scrapie to mice. J. Gen. Virol. 73, 1891–1897 (1992).

    Article  Google Scholar 

  6. Bruce, M. et al. Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Phil. Trans. R. Soc. Lond. B 343, 405–411 (1994).

    Article  ADS  CAS  Google Scholar 

  7. Foster, J. D., Bruce, M., McConnell, I., Chree, A. & Fraser, H. Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet. Rec. 138, 546–548 (1996).

    Article  CAS  Google Scholar 

  8. Fraser, H. et al. Transmission of feline spongiform encephalopathy to mice. Vet. Rec. 134, 449 (1994).

    Article  CAS  Google Scholar 

  9. Will, R. G. et al. Anew variant of Creutzfeldt–Jakob disease in the UK. Lancet 347, 921–925 (1996).

    Article  CAS  Google Scholar 

  10. Chazot, G. et al. New variant of Creutzfeldt–Jakob disease in a 26-year-old French man. Lancet 347, 1181 (1996).

    Article  CAS  Google Scholar 

  11. Cousens, S. N. et al. Sporadic Creutzfeldt–Jakob disease in the United Kingdom: epidemiological data from 1970–1996. Br. Med. J. 315, 389–396 (1997).

    Article  CAS  Google Scholar 

  12. Dickinson, A. G. in Slow Virus Diseases of Animals and Man (ed. Kimberlin, R. H.) 209–241 (North-Holland, Amsterdam, (1976)).

    Google Scholar 

  13. Carp, RI. & Callahan, S. M. Variation i nthe characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep. J. Gen. Virol. 72, 293–298 (1991).

    Article  Google Scholar 

  14. Fraser, H., Behan, W., Chree, A., Crossland, G. & Behan, P. Mouse inoculation studies reveal no transmissible agent in amyotrophic lateral sclerosis. Brain Pathol. 6, 89–99 (1996).

    Article  CAS  Google Scholar 

  15. Tateishi, J. Transmission of human prion diseases of rodents. Semin. Virol. 7, 175–180 (1996).

    Article  Google Scholar 

  16. Tateishi, J., Ohta, M., Koga, M., Sato, Y. & Kuroiwa, Y. Transmission of chronic spongiform encephalopathy with kuru plaques from humans to small rodents. Ann. Neurol. 5, 581–584 (1979).

    Article  CAS  Google Scholar 

  17. Tateishi, J. et al. First experimental transmission of fatal familial insomnia. Nature 376, 434–435 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Collinge, J., Sidle, K. C. L., Meads, J., Ironside, J. & Hill, A. F. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383, 685–690 (1996).

    Article  ADS  CAS  Google Scholar 

  19. Hill, A. F., Will, R. G., Ironside, J. & Collinge, J. Type of prion protein in UK farmers with Creutzfeldt–Jakob disease. Lancet 350, 188 (1997).

    Article  CAS  Google Scholar 

  20. Somerville, R. A. et al. Biochemical typing of scrapie strains. Nature 386, 564 (1997).

    Article  ADS  CAS  Google Scholar 

  21. Telling, G. et al. Evidence for the conformation of the pathological isoform of the prion protein enciphering and propagating prion diversity. Science 274, 2079–2082 (1996).

    Article  ADS  CAS  Google Scholar 

  22. Dickinson, A. G., Meikle, V. M. H. & Fraser, H. Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J. Comp. Pathol. 78, 293–299 (1968).

    Article  CAS  Google Scholar 

  23. Westaway, D. et al. Distinct prion proteins in short and long scrapie incubation period mice. Cell 51, 651–662 (1987).

    Article  CAS  Google Scholar 

  24. Fraser, H. & Dickinson, A. G. The sequential development of the brain lesions of scrapie in three strains of mice. J. Comp. Pathol. 78, 301–311 (1968).

    Article  CAS  Google Scholar 

  25. Farquhar, C. F. et al. in Transmissible Spongiform Encephalopathies (eds Bradley, R. & Marchant, B.) 301–313 (Commission of the European Communities, Brussels, (1994)).

    Google Scholar 

  26. Bell, J. E. et al. Prion protein immunocytochemistry — UK five centre consensus report. Neuropathol. Appl. Neurobiol. 23, 26–35 (1997).

    Article  CAS  Google Scholar 

  27. Kirkwood, B. R. Essentials of Medical Statistics (Blackwell, Oxford, (1988)).

    Google Scholar 

  28. Mardia, K. V., Kent, J. T. & Bibby, J. M. Multivariate Analysis (Academic, London, (1979)).

    MATH  Google Scholar 

Download references


We acknowledge the contribution of A. Dickinson, who pioneered TSE strain discrimiantion in the 1960s. We also thank M. Brady, F. Purdie, L. Hunter, K. Lamza, S. Mack and other staff at the Neuropathogenesis Unit for technical support. This work was supported by the Department of Health, MRC, BBSRC and MAFF.

Author information

Authors and Affiliations


Corresponding author

Correspondence to M. E. Bruce.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bruce, M., Will, R., Ironside, J. et al. Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 498–501 (1997).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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