The Rise and Fall of Modern Medicine

by James Le Fanu

  3.D. J. Ingle, ‘From A–F’, Pharos, July 1964, pp. 77–80.

  4.Michael Denton, Evolution: A Theory in Crisis (Bethesda, MD: Adler & Adler, 1986).

  PART II: THE END OF THE AGE OF OPTIMISM

  1: The Revolution Falters

  REFERENCES

  1.Office of Health Economics, Compendium of Health Statistics (Office of Health Economics, 1984).

  2.Colin Dollery, The End of an Age of Optimism (Nuffield Provincial Hospitals Trust, 1978).

  3.James B. Wyngaarden, ‘The Clinical Investigator as an Endangered Species’, NEJM, 1979, Vol. 301, pp. 1254–9.

  4.Editorial, ‘A Dearth of New Drugs’, Nature, 1980, Vol. 283, p. 609.

  5.Fred Steward and George Wibberley, ‘Drug Innovation: What’s Slowing it Down?’, Nature, 1980, Vol. 284, pp. 118–20.

  6.Sir Ronald Bodley-Scott (ed.), The Medical Annual (Bristol: John Wright & Sons, 1945–93).

  2: The Dearth of New Drugs

  REFERENCES

  1.Richard J. Wurtman and Robert L. Bettiker, ‘The Slowing of Treatment Discovery, 1965–95’, Nature Medicine, 1995, Vol. 1, pp. 1122–5. See also Joseph DiMasi, ‘New Drug Development in the United States, 1963–90’, Clinical Pharmacology and Therapeutics, 1991, Vol. 50, pp. 471–86.

  2.A. Willman, ‘Thalidomide and Foetal Abnormalities’, BMJ, 17 February 1962, p. 477. See also Editorial, ‘Thalidomide’s Long Shadow’, BMJ, 13 November 1976, pp. 1155–6.

  3.M. Weatherall, ‘An End to the Search for New Drugs?’, Nature, 1982, Vol. 296, pp. 387–90. See also Max Tishler, ‘Drug Discovery: Background and Foreground’, Clinical Pharmacology and Therapeutics, 1973, Vol. 14, pp. 479–86.

  4.J. W. Black and J. S. Stephenson, ‘Pharmacology of a New Adrenergic Beta Receptor Blocking Compound’, The Lancet, 1962, Vol. 2, pp. 311–15. See also J. W. Brimblecombe et al., ‘Cimetidine: A Non-thiourea H2 Receptor Antagonist’, Journal of International Medical Research, 1975, Vol. 3, pp. 86–92.

  5.Alan S. Perelson et al., Nature, 1997, Vol. 387, pp. 188–91. See also Editorial, ‘New Hope in HIV Disease’, Science, 1996, Vol. 279, pp. 1988–90; Mei-hwei Chang et al., ‘Universal Hepatitis B Vaccination in Taiwan and the Incidence of Hepato-cellular Cancer in Children’, NEJM, 1997, Vol. 336, pp. 1855–60.

  6.The top-ten pharmaceutical products in 1993 were as follows: Zantac, Renitec, Ciproxin, Voltaren, Zovirax, Capoten, Augmentin, Mevacor, Procardia and Prozac.

  7.Roger S. Rittmaster, ‘Finasteride’, NEJM, 1994, Vol. 330, pp. 120–4. See also G. J. Gormley et al., ‘The Effect of Finasteride in Men With Benign Prostatic Hyperplasia’, NEJM, 1992, Vol. 327,p. 1185.

  8.Richard Appleton, ‘The Anti-epileptic Drugs’, Archives of Disease in Childhood, 1996, Vol. 75, pp. 256–62. See also Gilles Mignot, ‘Drug Trials in Epilepsy: New Drugs Have Been Poorly Assessed’, BMJ, 1996, Vol. 313, p. 1157.

  9.W. I. McDonald, ‘New Treatments for Multiple Sclerosis’, BMJ, 1995, Vol. 310, pp. 345–7. See also Peter Harvey, ‘Why Interferon Beta 1B Was Licensed Is a Mystery’, BMJ, 1996, Vol. 313, pp. 297–8; Cornelius Kelly, ‘Drug Treatments for Alzheimer’s Disease’, BMJ, 1997, Vol. 314, pp. 693–4; Nicholas Wagner, ‘Local Committee Has Declined to Approve NHS Hospital Prescription of Donepezil’, BMJ, 1997, Vol. 314, p. 1555.

  10.Jill Rafuse, ‘US Industry Hurt by Rising Research Costs and Slump in Prices’, Canadian Medical Association Journal, 1994, Vol. 150, p. 130.

  11.John Griffin, ‘The Madness of Industry’s Mega Mergers’, Scrip Magazine, May 1996, pp. 10–11. See also Editorial, ‘Bigger Companies for Better Drugs’, The Lancet, 1995, Vol. 346, p. 585.

  12.James R. Broach and Jeremy Thorner, ‘High-Throughput Screening for Drug Discovery’, Nature, 1996, Vol. 384, pp. 14–16.

  3: Technology’s Failings

  GENERAL READING

  John Bunker, ‘Artificial Organs and Life-support Systems’, Encyclopaedia of Bioethics, Vol. 1, ed. Warren Thomas Reich (New York: Macmillan, 1978).

  Bryan Jennett, High Technology Medicine: Benefits and Burdens (Oxford: OUP, 1986).

  Tim Chard and Martin Richards, ‘Benefits and Hazards of the New Obstetrics’, Clinics in Developmental Medicine, 1977, No. 64.

  Anne Oakley, The Captured Womb (Oxford: Blackwell, 1984).

  REFERENCES

  1.J. A. Seibert, ‘100 Years of Diagnostic Imaging Technology’, Health Physics, 1995, Vol. 69, pp. 695–719.

  2.Katherine Petre et al., ‘PTCA in 1985–86 and 1977–81’, NEJM, 1998, Vol. 318, pp. 265–70.

  3.W. Y. Lau, ‘History of Endoscopic and Laparoscopic Surgery’, World Journal of Surgery, 1997, Vol. 21, pp. 444–53. See also P. J. Treacy and A. G. Johnson, ‘Is the Laparoscopic Bubble Bursting?’, The Lancet, 1995, Vol. 346, p. 23.

  4.M. E. Abrams, ‘Cost of Tests’, Journal of the Royal College of Physicians, 1979, Vol. 13, pp. 217–18. See also Bruce R. Smoller, ‘Phlebotomy for Diagnostic Laboratory Tests in Adults’, NEJM, 1986, Vol. 315, pp. 1233–5; John F. Burnum, ‘Medical Vampires’, NEJM, 1986, Vol. 315, p. 1250.

  5.Editorial, ‘Reducing Tests’, The Lancet, 1981, Vol. 1, pp. 539–40. See also Jonathan Showstack, ‘Changes in the Use of Medical Technology, 1972–77’, NEJM, 1982, Vol. 306, pp. 706–13; Paul F. Griner, ‘Misuse of Laboratory Tests and Diagnostic Procedures’, NEJM, 1982, Vol. 307, pp. 1336–9.

  6.M. L. Clark, ‘Upper Intestinal Endoscopy’, The Lancet, 1985, Vol. 1, p. 629. See also Howard M. Spiro, ‘My Kingdom for a Camera: Some Comments on Medical Technology’, NEJM, 1974, pp. 1070–2.

  7.Edward J. Quilligan and R. H. Paul, ‘Foetal Monitoring: Is it Worth it?’, Obstetrics and Gynaecology, 1975, Vol. 45, pp. 96–100.

  8.Ronald E. Miers, ‘Two Patterns of Perinatal Brain Damage and Their Conditions of Occurrence’, AJOG, 1972, Vol. 112, pp. 246–60.

  9.R. W. Beard et al., ‘The Significance of Changes in the Continuous Foetal Heart Rate in the First Stage of Labour’, Journal of Obstetrics and Gynaecology of the British Commonwealth, 1971, Vol. 78, pp. 865–81. See also R. W. Beard et al., ‘Intensive Care of the High-risk Foetus in Labour’, Journal of Obstetrics and Gynaecology of the British Commonwealth, 1971, Vol. 78, pp. 882–93; Raymond Kennedy, ‘Electronic Foetal Heart Rate Monitoring: Retrospective Reflections on a Twentieth-century Technology’, JRSM, 1998, Vol. 91, p. 244.

  10.William Arney, Monitoring and Surveillance in Power and the Profession of Obstetrics (Chicago, IL: University of Chicago Press, 1982).

  11.Compare Editorial, ‘Is Foetal Monitoring Worthwhile?’, BMJ, 6 March 1971, pp. 515–16 with G. S. Sykes et al., ‘Foetal Distress in the Condition of New-born Infants’, BMJ, 1983, Vol. 287, pp. 943–5; also correspondence, BMJ, 1984, Vol. 288, pp. 567–9 and Editorial, ‘Foetal Monitoring During Labour’, BMJ, 3 December 1983, pp. 1649–50.

  12.Donald Acheson, William Power Memorial Lecture, Department of Health, 1990.

  13.Dermot Macdonald, ‘Cerebral Palsy and Intrapartum Foetal Monitoring’, NEJM, Vol. 334, pp. 659–60. See also Adrian Grant et al., ‘Cerebral Palsy Among Children Born During the Dublin Randomised Trial of Intrapartum Monitoring’, The Lancet, 1989, Vol. 2, pp. 1233–5; Fiona Stanley, ‘Cerebral Palsy: The Courts Catch up With Sad Realities’, Medical Journal of Australia, 1994, Vol. 161, p. 236; David Hall, ‘Birth Asphyxia and Cerebral Palsy’, BMJ, 1989, Vol. 299, pp. 279–83; Eve Blair, ‘Intrapartum Asphyxia: A Rare Cause of Cerebral Palsy’, Journal of Paediatrics, 1988, Vol. 112, pp. 5125–519; Editorial, ‘Cerebral Palsy, Intrapartum Care and a Shot in the Foot’, The Lancet, 1989, Vol. 2, pp. 1251–2; Fritz K. Beller, ‘The Cerebral Palsy Story: A Catastrophic Misunderstanding in Obstetrics’, Obstetrical and Gynaecological Survey, 1995, Vol. 50, p. 83.

  14.R. S. Illingworth, ‘Why Blame the Obstetrician? A Review’, BMJ, 1979, Vol. 1, pp. 797–801.

  15.Quoted in Roy Porter, The Greatest Benefit to Mankind (HarperCollins, 1997).

  16.Muriel Gillick, ‘The High Cost of Dying’, Archives of Internal Medicine, 1994, Vol. 154, pp. 2134–7.
<
br />   17.David P. Schapira, ‘Intensive Care: Survival and Expense of Treating Critically Ill Cancer Patients’, JAMA, 1993, Vol. 269, pp. 783–6.

  18.Robert and Peggy Stinson, ‘On the Death of a Baby’, Journal of Medical Ethics, 1981, Vol. 7, pp. 5–18.

  4: The Clinical Scientist as an Endangered Species

  REFERENCES

  1.James Wyngaarden, ‘The Clinical Investigator as an Endangered Species’, NEJM, 1969, Vol. 301, pp. 1254–9.

  2.BMJ, 1970, Vol. 1, pp. 1–58.

  3.Jonathan M. Glass, ‘The Proportion of the BMJ’s Editorials on Medical Subjects is Decreasing’, BMJ, 1996, Vol. 313, pp. 1503–4. See also Bruno Simini, ‘Randomised Control Trials’, The Lancet, 1998, Vol. 351, p. 682.

  4.BMJ, 1995, Vol. 310, pp. 1–70.

  5.Christopher C. Booth, ‘Clinical Research’, Historical Perspectives on the Role of the MRC, ed. Joan Austoker and Linda Bryder (Oxford: OUP, 1989). See also Editorial, ‘Brave New Hospital’, BMJ, 5 September 1970, p. 538; ‘Northwick Park Hospital and Clinical Research Centre’, BMJ, 5 September 1970, pp. 576–80.

  6.Editorial, ‘The Future of Clinical Research in Britain’, BMJ, 1986, Vol. 292, pp. 416–17. See also ‘A Boost for Clinical Research’, BMJ, 1986, Vol. 292, p. 362 and correspondence: Christopher Booth, BMJ, 1986, Vol. 292, p. 556; Richard Edwards, BMJ, 1986, Vol. 292, p. 619; Victor Hawthorne, BMJ 1986, Vol. 292, p. 830.

  7.Everett Vokes, ‘Combined Modality Therapy of Solid Tumours’, The Lancet, 1997, Vol. 349 (supplement II), pp. 4–6.

  PART III: THE FALL

  1: The Brave New World of The New Genetics

  GENERAL READING

  Walter Bodmer and Robin McKie, The Book of Man (Little, Brown,1994).

  Stephen S. Hall, Invisible Frontiers: The Race to Synthesise a Human Gene (Sidgwick & Jackson, 1988).

  Horace Freeland Judson, The Eighth Day of Creation: Makers of the Revolution of Biology (Penguin, 1979).

  Evelyn Fox Keller, Refiguring Life: Metaphors for Twentieth-Century Biology (New York: Columbia University Press, 1995).

  Daniel J. Kevles and Leroy Hood, The Code of Codes (Cambridge, MA: Harvard University Press, 1992).

  Dorothy Nelkin and M. Susan Lindee, The DNA Mystique: The Gene as a Cultural Icon (New York: W. H. Freeman, 1995).

  Robert Shapiro, The Human Blueprint: The Race to Unlock the Secrets of Our Genetic Script (Cassell, 1992).

  James D. Watson, The Double Helix (Weidenfeld & Nicolson, 1997)

  David Weatherall, The New Genetics and Clinical Practice (Oxford: OUP, 1991).

  ——, Science and the Quiet Art (Oxford: OUP, 1993).

  Tom Wilkie, Perilous Knowledge (Faber & Faber, 1993).

  Christopher Wills, Exons, Introns and Talking Genes: The Science Behind the Human Genome Project (Oxford: OUP, 1992).

  REFERENCES

  1.John Saville, ‘Prospecting for Gold in the Human Genome’, BMJ, 1997. Vol. 314, pp. 43–9.

  2.J. D. Watson and F. H. C. Crick, ‘Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid’, Nature, 1953, Vol. 171, p. 737.

  3.J. D. Watson and F. H. C. Crick, ‘Genetic Implications of the Structure of DNA’, Nature, 1953, Vol. 171, pp. 964–6.

  4.F. H. C. Crick, ‘On Protein Synthesis’, Symposia of the Society for Experimental Biology (Cambridge: Cambridge University Press, 1958), pp. 138–53.

  5.Joshua Lederberg, ‘What the Double Helix Has Meant for Basic Medical Science’, JAMA, 1993, Vol. 269, pp. 1981–5. See also Victor McKusick, ‘Medical Genetics: A Forty-year Perspective on the Evolution of a Medical Specialty from a Basic Science’, JAMA, 1993, Vol. 270, pp. 2351–6; Irwin Chargaff, ‘Preface to a Grammar of Biology: 100 Years of Nucleic Acid Research’, Science, 1971, Vol. 172, pp. 637–42; Gunther S. Stent, ‘That Was the Molecular Biology That Was’, Science, 1968, Vol. 160, pp. 390–5.

  6.Christopher Wills, Exons, Introns and Talking Genes.

  7.David Weatherall, Science and the Quiet Art.

  8.Maxim Frank-Kamenetskii, Unravelling DNA (New York: Wiley-VCH, 1993).

  9.Hamilton O. Smith, ‘Nobel Lectures: Physiology or Medicine, 1971–80’, World Scientific, 1992, pp. 523–43.

  10.Stanley N. Cohen et al., ‘Construction of Biologically Functional Bacterial Plasmids in Vitro’, Proceedings of the National Academy of Science, 1973, Vol. 70, pp. 3240–4. See also Stanley N. Cohen, ‘The Manipulation of Genes’, Scientific American, 1975, pp. 25–33.

  11.David Baltimore, ‘RNA-dependent DNA Polymerase in Virions of RNA Tumour Viruses’, Nature, 1970, Vol. 226, pp. 1209–11; Howard M. Temin, ‘RNA-dependent DNA Preliminaries in Virions of Rouse Sarcoma Virus’, Nature, 1970, Vol. 226, pp. 1211–13; David Baltimore, ‘Nobel Lectures: Physiology or Medicine, 1971–80’, World Scientific, 1992, pp. 215–29.

  12.Axel Ullrich, ‘Rat Insulin Genes: Construction of Plasmids Containing the Coding Sequences’, Science, 1977, Vol. 196, pp. 1313–17. See also D. L. Kacian et al., ‘Decreased Globin Messenger RNA in Thalassaemia Detected by Molecular Hybridization’, Proceedings of the National Academy of Science, 1973, Vol. 70, pp. 1886–90.

  13.Frederick Sanger, ‘Determination of Nucleotide Sequences in DNA’, Science, 1981, Vol. 214, p. 1205. See also F. Sanger et al., ‘Nucleotide Sequence of Bacteriophage x174 DNA’, Nature, 1977, Vol. 265, p. 687.

  14.Walter Gilbert, ‘DNA Sequencing and Gene Structure’, Science, 1981, Vol. 214, p. 1305.

  15.David E. Comings, ‘Prenatal Diagnosis and the “New Genetics”’, American Journal of Human Genetics, 1980, Vol. 32, p. 453. See also David Weatherall, The New Genetics and Clinical Practice; Tony Smith, ‘How Will the New Genetics Work?’, BMJ, 1983, Vol. 286, pp. 1–2.

  16.Stephen S. Hall, Invisible Frontiers.

  17.Walter Bodmer and Robin McKie, The Book of Man.

  18.James Erlichman, Guardian, 15 September 1982.

  19.Joseph Eschbach, ‘Correction of the Anaemia of End-stage Renal Disease With Recombinant Human Erythropoietin’, NEJM, 1987, Vol. 316, pp. 73–8.

  20.Martin Gore et al., ‘Tumour Marker Level During Marimastat Therapy’, The Lancet, 1996, Vol. 348, p. 263. See also W. Wayt Gibbs, ‘State of Shock: Sepsis Can Be Fatal to Firms as well as to Patients’, Scientific American, October 1994, pp. 107–8; Editorial, ‘Biotech’s Uncertain Future’, The Lancet, 1996, Vol. 347, p. 1497.

  21.Judy C. Chang and Yuet Wai Kan, ‘A Sensitive New Prenatal Test for Sickle Cell Anaemia’, NEJM, 1982, Vol. 307, pp. 30–31. See also Henry M. Kronenberg, ‘Looking at Genes’, NEJM, 1982, Vol. 307, pp. 50–2.

  22.Michael Angastiniotis et al., ‘How Thalassaemia Was Controlled in Cyprus’, World Health Forum, 1986, Vol. 7, pp. 291–7.

  23.David J. H. Brock, ‘Prenatal Screening for Cystic Fibrosis: Five Years’ Experience Reviewed’, The Lancet, 1996, Vol. 347, pp. 148–50. See also Editorial, ‘Screening for Cystic Fibrosis’, The Lancet, 1992, Vol. 340, pp. 209–10; Matthew John Smith, ‘An Evaluation of Population Screening for Carriers of Cystic Fibrosis’, Journal of Public Health Medicine, 1992, Vol. 14, pp. 257–63; M. E. Mennie et al., ‘Prenatal Screening for Cystic Fibrosis: Psychological Effect on Carriers and Their Partners’, Journal of Medical Genetics, 1993, Vol. 30, pp. 543–8; John Burn, ‘Screening for Cystic Fibrosis’, Primary Care, 1993, Vol. 306, pp. 1558–9; Nicholas J. Wald, ‘Couples Screening for Cystic Fibrosis’, The Lancet, 1991, Vol. 338, pp. 1318–19.

  24.Reed Edwin Pyeritz, ‘Family History and Genetic Risk Factors’, JAMA, 1997, Vol. 278, pp. 1284–5. See also Angus Clark, ‘Population Screening for Genetic Susceptibility to Disease’, BMJ, 1995, Vol. 311, pp. 35–7; Karol Sikora, ‘Genes, Dreams and Cancer’, BMJ, 1994, Vol. 308, pp. 1217–20.

  25.Amelia A. Langston, ‘BRCA1 Mutations in a Population-based Sample of Young Women With Breast Cancer’, NEJM, 1996, Vol. 334, pp. 137–42. See also Francis S. Collins, ‘BRCA1: Lots of Mutations, Lots of Dilemmas’, NEJM, 1996, Vol. 334, pp. 186–8; Rachel Nowak, ‘Many Mutations May Make Tests Difficult’, Science
, 1994, Vol. 266, p. 1470; Jean Marx, ‘A Second Breast Cancer Susceptibility Gene is Found’, Science, 1996, Vol. 271, pp. 30–1.

  26.Peter S. Harper, ‘Genetic Testing, Common Diseases and Health Service Provision’, The Lancet, 1995, Vol. 346, pp. 1645–6. See also Editorial, ‘Have You Had a Gene Test?’, The Lancet, 1996, Vol. 347, p. 133; correspondence: The Lancet, 1996, Vol. 347, p. 685; Ehsan Masood, ‘Gene Tests: Who Benefits from Risks’, Nature, 1996, Vol. 379, pp. 389–92.

  27.R. Michael Blaese, ‘T. Lymphocyte: Directed Gene Therapy for ADA-SCID – Initial Trial Results After Four Years’, Science, 1995, Vol. 270, pp. 475–9.

  28.W. French Anderson, ‘Human Gene Therapy’, Science, 1992, Vol. 256, pp. 808–13. See also Theodore Friedmann, ‘A Brief History of Gene Therapy’, Nature Genetics, 1992, Vol. 2, pp. 93–8; Manal A. Morsy, ‘Progress Toward Human Gene Therapy’, JAMA, 1993, Vol. 270, pp. 2338–46; A. Dusty Miller, ‘Human Gene Therapy Comes of Age’, Nature, 1992, Vol. 357, pp. 455–9.

  29.Eliot Marshal, ‘Less Hype, More Biology Needed for Gene Therapy’, Science, 1995, Vol. 270, p. 1751. See also Eliot Marshal, ‘Gene Therapy’s Growing Pains’, Science, 1995, Vol. 269, pp. 1050–5.

  30.Michael R. Knowles et al., ‘A Controlled Study of Adenoviral-Vector-Mediated Gene Transfer in the Nasal Epithelium of Patients With Cystic Fibrosis’, NEJM, 1995, Vol. 333, pp. 823–31.

  31.Jerry R. Mendell, ‘Myoblast Transfer in the Treatment of Duchenne’s Muscular Dystrophy’, NEJM, 1995, Vol. 333, pp. 832–8.

  32.Jeffrey M. Leiden, ‘Gene Therapy: Promise, Pitfalls and Prognosis’, NEJM, 1995, Vol. 333, pp. 871–3.

  33.Theodore Friedman, ‘Human Gene Therapy: An Immature Genie But Certainly Out of the Bottle’, Nature Medicine, 1996, Vol. 2, pp. 144–7.

  34.Meredith Wadman, ‘Review Panel Cancels Meeting as Gene Therapy Proposals Fall’, Nature, 1996, Vol. 379, p. 66.