, Volume 35, Supplement 2, pp S60–S68 | Cite as

Scientific and ethical consequences of disease prediction

  • M. Siegler
  • S. Amiel
  • J. Lantos


HLA-typing, gene analysis, anti-islet cell antibody testing and metabolic studies can identify people at high risk for developing Type 1 (insulin-dependent) diabetes mellitus prior to the onset of clinical disease. The positive predictive value of these tests is high in first degree relatives of patients with Type 1 diabetes, but six times less so in the general population, where disease incidence is much lower but where 90% of new cases occur. Multiple testing improves sensitivity but decreases specificity. Intervention strategies are being designed with the aim of delaying or preventing progression to clinical disease. The more invasive the intervention, the greater is the specificity required. The practical and ethical implications of identifying high risk of diabetes in healthy individuals are complex and require further research, but some lessons can be learned from the experience of other disease prediction programmes.

Key words

Disease prediction disease prevention ethics 


  1. 1.
    Lappe M, Gustafson J, Robbin R (1972) Ethical and social issues in screening for genetic disease. N Engl J Med 285: 1129–1132Google Scholar
  2. 2.
    Rothstein MA (1989) Medical screening and the employee health cost crisis. The Bureau of National Affairs, Washington, DCGoogle Scholar
  3. 3.
    Tarn AC, Smith CP, Spencer KM, Bottazzo GF, Gale EAM (1987) Type 1 (insulin-dependent) diabetes: a disease of slow clinical onset? Br Med J 294: 342–345Google Scholar
  4. 4.
    Gorsuch AN, Spencer KM, Lister J et al. (1981) The natural history of type 1 (insulin-dependent) diabetes mellitus: evidence of a long pro-diabetic prodrome. Lancet II: 1363–1365Google Scholar
  5. 5.
    Chase HP, Voss MA, Butler-Simon N, Hoops S, O'Brien D, Dobersen MJ (1987) Diagnosis of pro-type 1 diabetes. J Ped 111: 807–812Google Scholar
  6. 6.
    Vardi P, Crisa L, Jackson RA (1991) Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet cell antibody positive relatives of type 1 (insulin-dependent) diabetic patients. Diabetologia 34: 93–102Google Scholar
  7. 7.
    Dorman JS, Trucco M (1989) How much does HLA-DQ phenotype contribute to the incidence of type 1 diabetes in Allegheny County, PA? Diabetes 38 [Suppl 2]: 34AGoogle Scholar
  8. 8.
    Faustman D, Eisenbarth GS, Daley J, Breutmeyer J (1989) Abnormal T-lymphocyte subsets in type 1 diabetes. Diabetes 38: 1462–1468Google Scholar
  9. 9.
    Bonifacio E., Bingley PJ, Dean BM, Shattock M, Dunger D, Gale EAM (1990) Quantification of islet cell antibodies and prediction of insulin-dependent diabetes. Lancet 335: 147–149Google Scholar
  10. 10.
    Riley WJ, Maclaren NK, Krischer J et al. (1990) A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. New Engl J Med 323: 1167–1172Google Scholar
  11. 11.
    Colman PG, Eisenbarth GS (1988) Immunology of type 1 diabe-tes. In: Alberti KGMM, Krall LP (eds) The diabetes annual/4. Elsevier, Amsterdam, pp 17–45Google Scholar
  12. 12.
    Bingley PJ, Shattock M, Chusney G et al. (1991) Unexpectedly high prevalence of islet cell antibodies in healthy children aged 8–13. Diabetic Med 8 [Suppl 1]: A3Google Scholar
  13. 13.
    Pauker SG, Kassirer JP (1987) Decision analysis. N Engl J Med 316: 250–258Google Scholar
  14. 14.
    Childs B, Gordis F, Kaback MM, Kazazian HG (1976) Tay-Sachs screening: motives for participating and knowledge of genetics and probability. Am J Hum Genet 28: 537–549Google Scholar
  15. 15.
    Fletcher JC (1984) Ethical and social aspects of risk predictions. Clin Genet 25: 25–32Google Scholar
  16. 16.
    Motulsky G (1989) Societal problems in human and medical genetics. Genome 31: 870–875Google Scholar
  17. 17.
    Beutler E, Boggs DR, Heller P et al. (1971) Hazards of indiscriminate screening for sickling. N Engl J Med 285: 1485–1486Google Scholar
  18. 18.
    Jenkins JB, Conneally PM (1989) The paradigm of Huntington's disease. Am J Hum Genet 45: 169–175Google Scholar
  19. 19.
    Markel DS, Young AB, Penney JB (1987) At-risk persons' attitudes toward presymptomatic and prenatal testing of Huntington's disease in Michigan. Am J Med Genet 26: 295–305Google Scholar
  20. 20.
    Meissen GJ, Berchek RL (1987) Intended use of predictive testing by those at risk for Huntington's disease. Am J Med Genet 26: 283–293Google Scholar
  21. 21.
    Quaid KA, Brandt J, Faden RR, Folstein SE (1989) Knowledge, attitude, and the decision to be tested for Huntington's disease. Clin Genet 36: 431–438Google Scholar
  22. 22.
    Craufurd D, Dodge A, Kerzin-Storrar L, Harris R (1989) Uptake of presymptomatic predictive testing for Huntington's disease. Lancet II: 603–605Google Scholar
  23. 23.
    Shaw MW (1987) Testing for the Huntington gene: a right not to know, a right to know, or a duty to know. Am J Med Genet 26: 243–246Google Scholar
  24. 24.
    Wilfond BS, Fost N (1990) The cystic fibrosis gene: medical and social implications for heterozygote detection. JAMA 263: 2777–2783Google Scholar
  25. 25.
    Roberts L (1990) To test or not to test. Science 247: 17–19Google Scholar
  26. 26.
    Caskey CT, Kaback MM, Beaudet AL (1990) The American Society of Human Genetics statement on cystic fibrosis. Am J Hum Genet 46: 393Google Scholar
  27. 27.
    Pauker SG, Pauker SP (1987) Prescriptive models to support decision making in genetics. Birth Defects 23: 279–296Google Scholar
  28. 28.
    Fletcher JC (1984) Ethical and social aspects of risk predictions. Clin Genet 25: 25–32Google Scholar
  29. 29.
    Motulsky AG (1989) Societal problems in human and medical genetics. Genome 31: 870–875Google Scholar
  30. 30.
    McNeil BJ, Weichselbaum R, Pauker SG (1981) Speech and survival: tradeoffs between quality and quantity of life in laryngeal cancer. N Engl J Med 305: 982–987Google Scholar
  31. 31.
    Kodish E, Lantos J, Stocking C, Singer PA, Siegler M, Johnson FL (1991) Bone marrow transplantation for sickle cell disease: a study of parents' decisions. N Engl J Med 325: 1349–1353Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • M. Siegler
    • 1
  • S. Amiel
    • 2
  • J. Lantos
    • 3
  1. 1.Center for Clinical Medical EthicsUniversity of ChicagoChicagoUSA
  2. 2.Unit for Metabolic MedicineGuy's HospitalLondonUK
  3. 3.La Rabida HospitalChicagoUSA

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