Line Cell Saga — An Argument in Favor of Production of Biologics in Cancer Cells

  • Maurice R. Hilleman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 118)


William Shakespeare observed that “All the world’s a stage and all the men and women merely players’.” This is no less true for those who act out the events of science than for thespians who pursue a career in the theater. It is amply illustrated in the drama that has attended the evolution of the dogma for acceptability or nonacceptability of particular kinds of cell cultures for preparing biologic products for use in man. Even cursory review leads to the conclusion that ill-conceived fears, preconceived notions, and personalities have contributed as much, perhaps, to decisionmaking as has science itself in this area of activity in which the scientific fact base is less than definitive.


Primary Cell Culture Rubella Virus Continuous Cell Line SV40 Virus Marburg Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hilleman, M. R. Cells, vaccines, and the pursuit of precedent. National Cancer Institute Monograph No. 29, pp 463–469. 1968.PubMedGoogle Scholar
  2. 2.
    Hilleman, M.R. Cells, vaccines, and safety for man. Biohazards in Biological Research. Edited by A. Hellman, M.N. Oxman, R. Pollack. Cold Spring Harbor Laboratory, 1973, pp 81–95.Google Scholar
  3. 3.
    Hilleman, M.R. Prospects for vaccines against cancer. Viruses, Evolution and Cancer. Edited by E. Kurstak and K. Maramorosch. New York, Academic Press, Inc., 1974, pp 549–560.Google Scholar
  4. 4.
    Hilleman, M.R. and Werner J.H. Recovery of new agent from patients with acute respiratory illness. Proc. Soc. Exp. Biol. Med. 85:183–188, 1954.PubMedGoogle Scholar
  5. 5.
    Biological Products, Public Health Service Regulations, Title 42, Part 73. U.S. Department of Health, Education, and Welfare, Publication 437 (revised Jan. 1967)Google Scholar
  6. 6.
    Hayflick, L. and Moorhead, P.S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:585–621, 1961.CrossRefGoogle Scholar
  7. 7.
    Continuously cultured tissue cells and viral vaccines. Report of a committee on tissue culture viruses and vaccines. Science 139:15–20, 1963.CrossRefGoogle Scholar
  8. 8.
    Hayflick, L., Moorhead, P.S., Pomerat C.M. et al: Choice of a cell system for vaccine production. Science 140:766–768, 1963.Google Scholar
  9. 9.
    Sabin, A.B. Cancer and human cell vaccines. Science J A5:33, 1969.Google Scholar
  10. 10.
    Hayflick, L. Dangerous vaccines. Science J A5:33, 1969.Google Scholar
  11. 11.
    Sabin, A.B. Gamma globulin prophylaxis; inactivated rubella virus; production and biologics control of live attenuated rubella virus vaccines. Discussion on Session V. Amer. J. Dis. Child 118:378–381, 1969.Google Scholar
  12. 12.
    Perkins, F.T. and Hayflick, L. Cell cultures. Science 155: 723–724, 1967.PubMedCrossRefGoogle Scholar
  13. 13.
    Andreopoulos, S. Human vaccines and bureaucracy: Stanford professor’s Odyssey. Stanford, MD 11:18–22, 1972.Google Scholar
  14. 14.
    Petricciani, J.C. Vaccine developments and the public interest. Stanford, MD 11:13–16, 1972.Google Scholar
  15. 15.
    Petricciani, J.C, Milstien, J.B., Seifried, A.S., et al. Safety of viral vaccine cell substrates: A reevaluation. J. Natl. Cancer Inst. 57:915–919, 1976.PubMedGoogle Scholar
  16. 16.
    Petricciani, J.C, Hopps, H.E., and Lorenz, D.E. Human virus vaccines: Why monkey cells? Science 176:813–14, 1972.CrossRefGoogle Scholar
  17. 17.
    Minutes of the Third Meeting of the Committee on Cell Cultures, International Association of Microbiological Societies, Permanent Section of Microbiological Standardization, Philadelphia May 18, 1966.Google Scholar
  18. 18.
    Developments in Biological Standardization. Volume 37. Edited by F.T. Perkins and R.H. Regamey. Switzerland, S. Karger, 1977.Google Scholar
  19. 19.
    Girardi A.J., Sweet, B.H., Slotnick, V.B. et al Development of tumors in hamsters inoculated in the neonatal period with vacuolating virus, SV40. Proc. Soc. Exp. Biol. Med. 109: 649–660, 1962.Google Scholar
  20. 20.
    Gear J.S.S., Cassel G.A., Gear A.J., et al. Outbreak of Marburg virus disease in Johannesburg. British Med. J. 4: 489–493, 1975.CrossRefGoogle Scholar
  21. 21.
    Cockburn, W.C. Poliomyelitis vaccination in tropical countries. Advances in Experimental Medicine and Biology. Edited by A Kohn and M.A. Klingberg. New York, Plenum Press, 1972, pp 223–236.Google Scholar
  22. 22.
    Hilleman, M.R., Bertland, A.U., Buynak, E.B., et al Clinical and laboratory studies of hepatitis B surface antigen vaccine. Viral Hepatitis. Edited by G.N. Vyas, S.N. Cohen, and R. Schmid. Philadelphia, Franklin Institute Press, 1978.Google Scholar
  23. 23.
    MacNab, G.M, Alexander, J.J., Lecatsas, G., et al. Hepatitis B surface antigen produced by a human hepatoma cell line. Br. J. Cancer 34:509–515, 1976.PubMedCrossRefGoogle Scholar
  24. 24.
    Memorandum: Interferon and other antiviral agents, with special reference to influenza. Bull WHO 56:229–240, 1978.Google Scholar
  25. 25.
    Hirsch, M.S. Interferon — its hour come at last? N. Eng. J. Med. 298:1022–1023, 1978.CrossRefGoogle Scholar
  26. 26.
    Merigan, T.C., Rand, K.H., Pollard, R.B., et al Human leukocyte interferon for the treatment of herpes zoster in patients with cancer. N. Eng. J. Med. 298:981–987, 1978.CrossRefGoogle Scholar
  27. 27.
    Strander, H. Mogensen, K.E., and Cantell, K. Production of human lymphoblastoid interferon. J. Clin. Microbiology 1: 116–117, 1975.Google Scholar
  28. 28.
    Zoon, K.C., Buckler, C.E., Bridgen, P.J., et al. Production of human lymphoblastoid interferon by Namalva cells. J. Clin. Microbiology 7:44–51, 1978.Google Scholar
  29. 29.
    Andersson-Anvret, M. and Lindahl, T. Integrated viral DNA sequences in Epstein-Barr virus-converted human lymphoma lines. J. Virology 25:710–718, 1978.PubMedGoogle Scholar
  30. 30.
    Pagano, J.S. The Epstein-Barr viral genome and its interactions with human lymphoblastoid cells and chromosomes. Viruses, Evolution and Cancer. Edited by E. Kurstak and K. Maramorosch. New York, Academic Press, Inc., 1974, pp 79–116.Google Scholar
  31. 31.
    Pritchett, R., Pedersen, M., and Kieff, E. Complexity of EBV homologous DNA in continuous lymphoblastoid cell lines. Virology 74:227–231, 1976.CrossRefGoogle Scholar
  32. 32.
    Doerfier, W. Integration of the deoxyribonucleic acid of adenovirus type 12 into the deoxyribonucleic acid of baby hamster kidney cells. J. Virology 6:652–666, 1970.Google Scholar
  33. 33.
    Botchan, M., Topp, W., and Sambrook, J. The arrangement of Simian virus 40 sequences in the DNA of transformed cells. Cell 9:269–287, 1976.PubMedCrossRefGoogle Scholar
  34. 34.
    Harnden, D.G. Chromosome abnormalities and predispostion towards cancer. Proc. Roy.Soc. Med. 69:41–43, 1976.PubMedGoogle Scholar
  35. 35.
    Levan A., Levan, G., and Mitelman, F. Chromosomes and cancer. Hereditas 86:15–30, 1977.PubMedCrossRefGoogle Scholar
  36. 36.
    Chromosomes and cancer. The Lancet ii:227–228, 1977.Google Scholar
  37. 37.
    Deoxyribonuclease I (Bovine pancreas). Worthington Enzyme Manual. Edited by L.A. Decker. New Jersey, Worthington Biochemical Corporation, 1977, pp 153–155.Google Scholar
  38. 38.
    Laskowski, M., Sr. Deoxyribonuclease I. The Enzymes. Third Edition. Edited by P.D. Boyer. New York, Academic Press, Inc., 1971, pp 289–311.Google Scholar
  39. 39.
    Smart, J.E. and Bonner, J. Studies on the role of histones in relation to the template activity and precipitability of chromatin at physiological ionic strengths. J. Mol. Biol 58:675–684. 1971.PubMedCrossRefGoogle Scholar
  40. 40.
    Harper H.A., Rodwell, V.W., Mayes, P.A., et al. Protein synthesis and the genetic code. Review of Physiological Chemistry. Sixteenth Edition. California, Lange Medical Publications, 1977, pp 433–447.Google Scholar
  41. 41.
    Fleckenstein, B., Daniel, M.D., Hunt, R.D. et al. Tumour induction with DNA of oncogenic primate herpesviruses. Nature 274:57–59, 1978.PubMedCrossRefGoogle Scholar
  42. 42.
    Sol, C.J.A. and van der Noordaa, J. Oncogenicity of SV40 DNA in the Syrian hamster. J. Gen. Virol. 37:635–638. 1977.CrossRefGoogle Scholar
  43. 43.
    Igarashi, K., Sasada, R., Kurokawa, T., et al. Biochemical studies on bovine adenovirus type 3. IV. Transformation by viral DNA and DNA fragments. J. Virol. 28:219–226. 1978.Google Scholar
  44. 44.
    Staehelin, M. Reaction of tobacco mosaic virus nucleic acid with formaldehyde. Biochimica et Biophysica Acta 29: 410–417, 1958.PubMedCrossRefGoogle Scholar
  45. 45.
    Feldman, M.Y. Reactions of nucleic acids and nucleoproteins with formaldehyde. Progress in Nucleic Acid Research and Molecular Biology. Volume 13. Edited by J.N. Davidson and W.E. Cohn. New York, Academic Press, 1973. pp 1–49.Google Scholar
  46. 46.
    Sarkar, N.K. and Dounce, A.L. A spectroscopic study of the reaction of formaldehyde with deoxyribonucleic and ribonucleic acid. Biochimica et Biophysica Acta 49:160–169, 1961.PubMedCrossRefGoogle Scholar
  47. 47.
    Pope, J.H., Horne, M.K., and Scott, W. Transformation of foetal human leukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int. J. Cancer 3:857–866, 1968.PubMedCrossRefGoogle Scholar
  48. 48.
    Katsuki, T. and Hinuma, Y. Characteristics of cell lines derived from human leukocytes transformed by different strains of Epstein-Barr virus. Int. J. Cancer 15:203–210, 1975.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • Maurice R. Hilleman
    • 1
  1. 1.Division of Virus & Cell Biology ResearchMerck Institute for Therapeutic ResearchWest PointUSA

Personalised recommendations