46 - Cause and Effect

05/20/19 • 38 min

Does smoking cause lung cancer? How could you ever know? The second in a three-part series on causality, I’m joined by Dr. Shoshana Herzig to discuss how Austin Bradford Hill and Richard Doll set out to try and answer this question -- and along the way revolutionized the way we think about what causes disease. In this episode, we’ll talk about the first double-blinded randomized controlled trial, the long shadow of tuberculosis, and why epidemiology is beautiful. Plus, a brand new #AdamAnswers about chest compressions!

Please support Bedside Rounds by filling out the listener demographic survey: https://survey.libsyn.com/bedsiderounds

Sources:

Bost TC. Cardiac arrest during anaesthesia and surgical operations. Am J Surg 1952;83: 135-4
Council, T. Tobacco Smoking and Lung Cancer. Brit Med J 1, 1523 (1957).
Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534.
Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168.
Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957).
Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956).
Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950).
Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965).
HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
Hurt R, Modern cardiopulmonary resuscitation—not so new after all. J R Soc Med. 2005 Jul; 98(7): 327–331.
Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009.
Keith A, Three Hunterian Lectures ON THE MECHANISM UNDERLYING THE VARIOUS METHODS OF ARTIFICIAL RESPIRATION PRACTISED SINCE THE FOUNDATION OF THE ROYAL HUMANE SOCIETY IN 1774. (1909). The Lancet, 173(4464), 825–828.
Kouwenhoven WB et al, Closed-chest cardiac massage, JAMA, JAMA. 1960;173(10):1064-1067.
Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004).
Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).

Please support Bedside Rounds by filling out the listener demographic survey: https://survey.libsyn.com/bedsiderounds

Sources:

Bost TC. Cardiac arrest during anaesthesia and surgical operations. Am J Surg 1952;83: 135-4
Council, T. Tobacco Smoking and Lung Cancer. Brit Med J 1, 1523 (1957).
Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534.
Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168.
Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957).
Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956).
Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950).
Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965).
HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
Hurt R, Modern cardiopulmonary resuscitation—not so new after all. J R Soc Med. 2005 Jul; 98(7): 327–331.
Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009.
Keith A, Three Hunterian Lectures ON THE MECHANISM UNDERLYING THE VARIOUS METHODS OF ARTIFICIAL RESPIRATION PRACTISED SINCE THE FOUNDATION OF THE ROYAL HUMANE SOCIETY IN 1774. (1909). The Lancet, 173(4464), 825–828.
Kouwenhoven WB et al, Closed-chest cardiac massage, JAMA, JAMA. 1960;173(10):1064-1067.
Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004).
Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).

Previous Episode

45 - The French Disease at 500

In 1495, a mysterious and deadly plague struck the city of Naples. Over the next 500 years, the medical attempts to understand and treat this new disease -- syphilis -- would mold and shape medicine in surprising ways. In this episode, Tony Breu and I will perform an historical and physiological biography of syphilis, covering the development of germ theory, epic poetry, mercury saunas, intentionally infecting patients with malaria, magic bullets, and lots and lots of experiments on poor rabbits. This presentation was performed live at the American College of Physicians’ national meeting in Philadelphia on April 11, 2019.

Sources (WARNING -- LONG LIST):

Swain, K. ‘Extraordinarily arduous and fraught with danger’: syphilis, Salvarsan, and general paresis of the insane. Lancet Psychiatry 5, (2018).
Kępa, M. et al. Analysis of mercury levels in historical bone material from syphilitic subjects – pilot studies (short report). Kępa Małgorzata 69, 367-377(11) (2012).
Forrai, J. Syphilis - Recognition, Description and Diagnosis. (2011). doi:10.5772/24205
Parascandola, J. From mercury to miracle drugs: syphilis therapy over the centuries. Pharm Hist 51, 14–23 (2009).
Eisler, C. Who Is Dürer’s ‘Syphilitic Man’? Perspect Biol Med 52, 48–60 (2009).
Rothschild, B. M. History of Syphilis. Clin Infect Dis 40, 1454–1463 (2005).
Schwartz, R. S. Paul Ehrlich’s Magic Bullets. New Engl J Medicine 350, 1079–1080 (2004).
Fee, E. The wages of sin. Lancet 354, SIV61 (1999).
O’Shea, J. ‘Two Minutes with Venus, Two Years with Mercury’-Mercury as an Antisyphilitic Chemotherapeutic Agent. J Roy Soc Med 83, 392–395 (1989).
Mahoney, J., Arnold, R., Sterner, B. L., Harris, A. & Zwally, M. Penicillin Treatment of Early Syphilis: II. Jama 251, 2005–2010 (1984).
Waugh, M. Role played by Italy in the history of syphilis. Sex Transm Infect 58, 92–95 (1982).
Thorburn, A. Fritz Richard Schaudinn, 1871-1906: protozoologist of syphilis. Sex Transm Infect 47, 459–461 (1971).
CROSBY, A. W. The Early History of Syphilis: A Reappraisal. Am Anthropol 71, 218–227 (1969).
Clark, E. G. & Danbolt, N. The Oslo study of the natural history of untreated syphilis An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material a review and appraisal. J Chron Dis 2, 311–344 (1955).
MUNGER, R. S. Guaiacum, the Holy Wood from the New World. J Hist Med All Sci IV, 196–229 (1949).
Thomas, E. & r, W. Rapid Treatment of Early Syphilis with Multiple Injections of Mapharsen. J Nerv Ment Dis 99, 88 (1944).
WIEDER, L., FOERSTER, O. & FOERSTER, H. MAPHARSEN IN THE TREATMENT OF SYPHILIS: FURTHER EXPERIENCES. Arch Dermatol Syph 35, 402–413 (1937).
THON, L. SHOULD THE INTERNIST KNOW SYPHILIS? J Amer Med Assoc 97, 994–996 (1931).
Sarton, G. The Earliest Printed Literature on Syphilis, being Ten Tractates from the Years 1495-1498. Karl Sudhoff , Charles Singer , Henry E. Sigerist. Isis 8, 351–354 (1926).
COLE, H., GERICKE, A. & SOLLMANN, T. THE TREATMENT OF SYPHILIS BY MERCURY INHALATIONS: HISTORY, METHOD AND RESULTS. Arch Dermatol Syph 5, 18–33 (1922).
Mason, U. Observation: Use and Abuse of Salvarsan. J Natl Med Assoc 3, 340–3 (1911).
Fleming, A. & Colebrook, L. ON THE USE OF SALVARSAN IN THE TREATMENT OF SYPHILIS. Lancet 177, 1631–1634 (1911).
Evans, A. The Treatment of Syphilis by Salvarsan (Dioxy-diamido-arseno-benzol). Brit Med J 1, 617 (1911).
Boeck, W. History, Theory and Practice of Syphilisation. New Engl J Medicine 73, 20–25 (1865).
Veale, H. Remarks on Syphilis and Its Treatment. Edinb Medical J 10, 10–26 (1864).
LaFond RE and Lukehart SA, Biological Basis for Syphilis. Clinical Microbiology Reviews 2006.
Secher L et al, Treponema pallidum in peripheral nerve tissue of syphilitic chancres. Acta dermato-venereologica 1982.
Hollander DH, Turner TB, The role of temperature in experimental treponemal infection. American journal of syphilis, gonorrhea, and venereal diseases, 1954
Eagle H, et al. The effect of hyperpyrexia on the therapeutic efficacy of penicillin in experimental syphilis. American journal of syphilis, gonorrhea, and venereal diseases, 1947.
Kampmeier RH, Syphilis therapy: an historical perspective. Journal of the American Venereal Disease Association 1976.
Pachner AR, Spirochetal Diseases of the CNS. Neurologic clinics, 1986.
Sell S et al, Experimental syphilitic orchitis in ...

Next Episode

47 - The Criteria

Can we ever know what causes a chronic disease? In this episode, I’m joined again by Dr. Shoshana Herzig to finish a three-part miniseries on Bradford Hill and Doll’s attempts to prove that smoking caused lung cancer. We’ll talk about the first prospective cohort trial in history, 1960s “Fake News” from tobacco companies, public spats with the most famous statistician of the 20th century, and the development of the Bradford Hill Criteria, a guideline, however imperfect, that gives doctors a blueprint to finally figure out what causes diseases.

Sources:

Crofton J, The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line. J R Soc Med. 2006 Oct; 99(10): 531–534.
Daniels M and Bradford Hill A, Chemotherapy of Pulmonary Tuberculosis in Young Adults, Br Med J. 1952 May 31; 1(4769): 1162–1168.
Dangers of Cigarette-smoking. Brit Med J 1, 1518 (1957).
Doll, R. & Hill, B. A. Lung Cancer and Other Causes of Death in Relation to Smoking. Brit Med J 2, 1071 (1956).
Doll, R. & Hill, B. A. Smoking and Carcinoma of the Lung. Brit Med J 2, 739 (1950).
Hill, A. The Environment and Disease: Association or Causation? J Roy Soc Med 58, 295–300 (1965).
HOFFMAN, F. L. CANCER AND SMOKING HABITS. Ann Surg 93, 50–67 (1931).
Keating C, Smoking Kills: The Revolutionary Life of Richard Doll. 2009.
Morabia, A. Quality, originality, and significance of the 1939 “Tobacco consumption and lung carcinoma” article by Mueller, including translation of a section of the paper. Prev Med 55, 171–177 (2012).
Ochsner, A. & bakey. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1, 109–25 (1999).
Ochsner, A. My first recognition of the relationship of smoking and lung cancer. Prev Med 2, 611–614 (1973).
Parascandola, M. Two approaches to etiology: the debate over smoking and lung cancer in the 1950s. Endeavour 28, 81–86 (2004).
Phillips, C. V. & Goodman, K. J. The missed lessons of Sir Austin Bradford Hill. Epidemiologic Perspectives Innovations 1, 1–5 (2004).
Proctor, R. Angel H Roffo: the forgotten father of experimental tobacco carcinogenesis. B World Health Organ 84, 494–495 (2006).
Wynder, E. RE: “WHEN GENIUS ERRS: R. A. FISHER AND THE LUNG CANCER CONTROVERSY”. Am J Epidemiol 134, 1467–9 (1991).