Skip to main content
PMC home page
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1976 May;49(2):175–195.

Causation and Disease: The Henle-Koch Postulates Revisited 1

Alfred S Evans
PMCID: PMC2595276  PMID: 782050

Abstract

The Henle-Koch postulates are reviewed in terms of their full validity in Koch's day and in light of subsequent developments. The changing guidelines developed for viral diseases, for viruses in relation to cancer and to chronic central nervous system infection, and for causative agents in chronic diseases are discussed chronologically. A set of guidelines for both acute infectious and chronic diseases is presented. The need for recognizing the role of the host and the spectrum of host responses, for sound biologic sense in evaluating causal roles of agents in disease, and for flexibility in adapting our guidelines to new knowledge are emphasized.

Full text

PDF

Images in this article

176FIG. 1
on p.176
176FIG. 2
on p.176
178FIG. 3
on p.178
180FIG. 4
on p.180
183FIG. 5
on p.183
185FIG. 6
on p.185
189FIG. 7
on p.189
190FIG. 8
on p.190

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam E., Rawls W. E., Melnick J. L. The association of herpesvirus type 2 infection and cervical cancer. Prev Med. 1974 Mar;3(1):122–141. doi: 10.1016/0091-7435(74)90068-1. [DOI] [PubMed] [Google Scholar]
  2. BLUMBERG B. S., ALTER H. J., VISNICH S. A "NEW" ANTIGEN IN LEUKEMIA SERA. JAMA. 1965 Feb 15;191:541–546. doi: 10.1001/jama.1965.03080070025007. [DOI] [PubMed] [Google Scholar]
  3. BURKITT D. A sarcoma involving the jaws in African children. Br J Surg. 1958 Nov;46(197):218–223. doi: 10.1002/bjs.18004619704. [DOI] [PubMed] [Google Scholar]
  4. Bancroft W. H., Mundon F. K., Russell P. K. Detection of additional antigenic determinants of hepatitis B antigen. J Immunol. 1972 Oct;109(4):842–848. [PubMed] [Google Scholar]
  5. EPSTEIN M. A., ACHONG B. G., BARR Y. M. VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA. Lancet. 1964 Mar 28;1(7335):702–703. doi: 10.1016/s0140-6736(64)91524-7. [DOI] [PubMed] [Google Scholar]
  6. Epstein M. A., Hunt R. D., Rabin H. Pilot experiments with EB virus in owl monkeys (Aotus trivirgatus). I Reticuloproliferative disease in an inoculated animal. Int J Cancer. 1973 Sep 15;12(2):309–318. doi: 10.1002/ijc.2910120202. [DOI] [PubMed] [Google Scholar]
  7. Evans A. S. Clinical syndromes in adults caused by respiratory infection. Med Clin North Am. 1967 May;51(3):803–818. doi: 10.1016/s0025-7125(16)33048-6. [DOI] [PubMed] [Google Scholar]
  8. Evans A. S., Niederman J. C., McCollum R. W. Seroepidemiologic studies of infectious mononucleosis with EB virus. N Engl J Med. 1968 Nov 21;279(21):1121–1127. doi: 10.1056/NEJM196811212792101. [DOI] [PubMed] [Google Scholar]
  9. Evans A. S. Pettenkofer revisited: the life and contributions of Max von Pettenkofer (1818-1901). Yale J Biol Med. 1973 Jun;46(3):161–176. [PMC free article] [PubMed] [Google Scholar]
  10. FOX J. P., GELFAND H. M., LEBLANC D. R., CONWELL D. P. Studies on the development of natural immunity to poliomyelitis in Louisiana. I. Over-all plan, methods and observations as to patterns of seroimmunity in the study group. Am J Hyg. 1957 May;65(3):344–366. doi: 10.1093/oxfordjournals.aje.a119874. [DOI] [PubMed] [Google Scholar]
  11. Feorino P. M., Humphrey D. Mononucleosis-associated subacute sclerosing panencephalitis. Lancet. 1975 Sep 20;2(7934):530–532. doi: 10.1016/s0140-6736(75)90898-3. [DOI] [PubMed] [Google Scholar]
  12. Fox J. P., Hall C. E., Cooney M. K., Luce R. E., Kronmal R. A. The Seattle virus watch. II. Objectives, study population and its observation, data processing and summary of illnesses. Am J Epidemiol. 1972 Oct;96(4):270–285. doi: 10.1093/oxfordjournals.aje.a121458. [DOI] [PubMed] [Google Scholar]
  13. Gajdusek D. C. Kuru and Creutzfeldt-Jakob disease. Experimental models of noninflammatory degenerative slow virus disease of the central nervous system. Ann Clin Res. 1973 Oct;5(5):254–261. [PubMed] [Google Scholar]
  14. HUEBNER R. J. Criteria for etiologic association of prevalent viruses with prevalent diseases; the virologist's dilemma. Ann N Y Acad Sci. 1957 Apr 19;67(8):430–438. doi: 10.1111/j.1749-6632.1957.tb46066.x. [DOI] [PubMed] [Google Scholar]
  15. Hallee T. J., Evans A. S., Niederman J. C., Brooks C. M., Voegtly j. H. Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974 Sep;47(3):182–195. [PMC free article] [PubMed] [Google Scholar]
  16. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kieff E., Levine J. Homology between Burkitt herpes viral DNA and DNA in continuous lymphoblastoid cells from patients with infectious mononucleosis. Proc Natl Acad Sci U S A. 1974 Feb;71(2):355–358. doi: 10.1073/pnas.71.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klein G. The Epstein-Barr virus and neoplasia. N Engl J Med. 1975 Dec 25;293(26):1353–1357. doi: 10.1056/NEJM197512252932607. [DOI] [PubMed] [Google Scholar]
  19. Klemola E., Von Essen R., Henle G., Henle W. Infectious-mononucleosis-like disease with negative heterophil agglutination test. Clinical features in relation to Epstein-Barr virus and cytomegalovirus antibodies. J Infect Dis. 1970 Jun;121(6):608–614. doi: 10.1093/infdis/121.6.608. [DOI] [PubMed] [Google Scholar]
  20. Krugman S., Giles J. P., Hammond J. Infectious hepatitis. Evidence for two distinctive clinical, epidemiological, and immunological types of infection. JAMA. 1967 May 1;200(5):365–373. doi: 10.1001/jama.200.5.365. [DOI] [PubMed] [Google Scholar]
  21. Krugman S., Giles J. P. Viral hepatitis. New light on an old disease. JAMA. 1970 May 11;212(6):1019–1029. doi: 10.1001/jama.212.6.1019. [DOI] [PubMed] [Google Scholar]
  22. Kufe D., Magrath I. T., Ziegler J. L., Spiegelman S. Burkitt's tumors contain particles encapsulating RNA-instructed DNA polymerase and high molecular weight virus-related RNA. Proc Natl Acad Sci U S A. 1973 Mar;70(3):737–741. doi: 10.1073/pnas.70.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. LEVIN M. L. The occurrence of lung cancer in man. Acta Unio Int Contra Cancrum. 1953;9(3):531–541. [PubMed] [Google Scholar]
  24. Le Bouvier G. L. The heterogeneity of Australia antigen. J Infect Dis. 1971 Jun;123(6):671–675. doi: 10.1093/infdis/123.6.671. [DOI] [PubMed] [Google Scholar]
  25. Lilienfeld A. M. Epidemiology of infectious and non-infectious disease: some comparisons. Am J Epidemiol. 1973 Mar;97(3):135–147. doi: 10.1093/oxfordjournals.aje.a121494. [DOI] [PubMed] [Google Scholar]
  26. Miller G. The oncogenicity of Epstein-Barr virus. J Infect Dis. 1974 Aug;130(2):187–205. doi: 10.1093/infdis/130.2.187. [DOI] [PubMed] [Google Scholar]
  27. Narayan O., Penney J. B., Jr, Johnson R. T., Herndon R. M., Weiner L. P. Etiology of progressive multifocal leukoencephalopathy. Identification of papovavirus. N Engl J Med. 1973 Dec 13;289(24):1278–1282. doi: 10.1056/NEJM197312132892405. [DOI] [PubMed] [Google Scholar]
  28. Niederman J. C., McCollum R. W., Henle G., Henle W. Infectious mononucleosis. Clinical manifestations in relation to EB virus antibodies. JAMA. 1968 Jan 15;203(3):205–209. doi: 10.1001/jama.203.3.205. [DOI] [PubMed] [Google Scholar]
  29. Sawyer R. N., Evans A. S., Niederman J. C., McCollum R. W. Prospective studies of a group of Yale University freshmen. I. Occurrence of infectious mononucleosis. J Infect Dis. 1971 Mar;123(3):263–270. doi: 10.1093/infdis/123.3.263. [DOI] [PubMed] [Google Scholar]
  30. Shope R. E. SWINE INFLUENZA : III. FILTRATION EXPERIMENTS AND ETIOLOGY. J Exp Med. 1931 Jul 31;54(3):373–385. doi: 10.1084/jem.54.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stewart G. T. Limitations of the germ theory. Lancet. 1968 May 18;1(7551):1077–1081. doi: 10.1016/s0140-6736(68)91425-6. [DOI] [PubMed] [Google Scholar]
  32. Thomas H. E., Jr, Kannel W. B., Dawber T. R., McNamara P. M. Cholesterol-phospholipid ratio in the prediction of coronary heart disease. The Framingham study. N Engl J Med. 1966 Mar 31;274(13):701–705. doi: 10.1056/NEJM196603312741302. [DOI] [PubMed] [Google Scholar]
  33. WYNDER E. L., GRAHAM E. A. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. 1950 May 27;143(4):329–336. doi: 10.1001/jama.1950.02910390001001. [DOI] [PubMed] [Google Scholar]
  34. Weil M. L., Itabashi H., Cremer N. E., Oshiro L., Lennette E. H., Carnay L. Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. N Engl J Med. 1975 May 8;292(19):994–998. doi: 10.1056/NEJM197505082921903. [DOI] [PubMed] [Google Scholar]
  35. de Schryver A., Friberg S., Jr, Klein G., Henle W., Henle G., De-Thé G., Clifford P., Ho H. C. Epstein-Barr virus-associated antibody patterns in carcinoma of the post-nasal space. Clin Exp Immunol. 1969 Nov;5(5):443–459. [PMC free article] [PubMed] [Google Scholar]
  36. de Thé G., Geser A. A prospective sero-epidemiological study to investigate the role of EBV in Burkitt's lymphoma. Bibl Haematol. 1973;39:448–456. [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES