Research Ethics – A Short History

Quiz “Every treatment is an experiment”“Every treatment is an experiment”Author? Committee on medical research – 1941(FDR)Committee on medical research – 1941(FDR)Goals? August 19, 1947August 19, 1947 April 25, 1953April 25, 1953 December 23, 1954December 23, 1954 May 1960May 1960 March 19, 1960March 19, 1960 December 3, 1967December 3, 1967 August 5, 1968August 5, 1968 July 26, 1972July 26, 1972 July 25, 1978July 25, December 3, 1982December 3, 1982

“Every treatment is an experiment” Sir William Osler“Every treatment is an experiment” Sir William Osler Committee on medical research Effective military medicine-better soldiersCommittee on medical research Effective military medicine-better soldiers -1941(FDR) -1941(FDR) August 19, 1947 Doctors’ Trial at the Nuremberg TribunalAugust 19, 1947 Doctors’ Trial at the Nuremberg Tribunal April 25, 1953 DNA: The secret of lifeApril 25, 1953 DNA: The secret of life December 23, 1954 Renal transplantationDecember 23, 1954 Renal transplantation May 1960 Oral Contraceptives [Enovid FDA approved]May 1960 Oral Contraceptives [Enovid FDA approved] March 19, 1960 Chronic hemodialysis and the Seattle dialysisMarch 19, 1960 Chronic hemodialysis and the Seattle dialysis selection committee selection committee December 3, st heart transplantationDecember 3, st heart transplantation August 5, 1968 Harvard definition of brain deathAugust 5, 1968 Harvard definition of brain death July 26, 1972 The Tuskegee RevelationsJuly 26, 1972 The Tuskegee Revelations July 25, 1978 Baby Louise BrownJuly 25, 1978 Baby Louise Brown US Congress establishes National US Congress establishes National Commission for the Protection of Human Commission for the Protection of Human Subjects of Research Subjects of Research December 3, 1982 The Artificial HeartDecember 3, 1982 The Artificial Heart

The Doctors’ Trial at Nuremberg, 1947 The United States of America vs. Karl Brandt, et alThe United States of America vs. Karl Brandt, et al The first of 12 trialsThe first of 12 trials 23 defendants – all medial doctors accused of23 defendants – all medial doctors accused of involvement in Nazi human experimentation involvement in Nazi human experimentation

Nazi Experimentation included: StarvationStarvation Exposure to extreme cold and wetExposure to extreme cold and wet Wounding and infection w/bacteria, glass, dirt,etc.Wounding and infection w/bacteria, glass, dirt,etc. High altitude, compression chambersHigh altitude, compression chambers

Nazi Experimentation (cont’d) Malaria, TBMalaria, TB “Drinkable” sea water“Drinkable” sea water PoisonsPoisons Genetic studiesGenetic studies

Nuremberg Doctors’ Trial All 23 pleaded “not guilty”All 23 pleaded “not guilty” 5 acquitted, 11 prison sentences, 7 death sentences5 acquitted, 11 prison sentences, 7 death sentences

The Nuremberg Code – Directives for Human Experimentation 10 points10 points Voluntary consent, ability to withdrawVoluntary consent, ability to withdraw Goals – constraintsGoals – constraints

WMA Declaration of Helsinki – 1964 Ethical Principles for Medical Research Involving Human Subjects Basic Principles – 10Basic Principles – 10 (consent, proportionality, integrity) (consent, proportionality, integrity) Medical Research Combined with Clinical CareMedical Research Combined with Clinical Care (clinical research) (clinical research) dual goals: cure of this patient & acquisition of dual goals: cure of this patient & acquisition of new medical knowledge new medical knowledge potential conflict: potential conflict: potential conflicts of interest for clinician- potential conflicts of interest for clinician- investigators investigators Non-therapeutic research on human subjectsNon-therapeutic research on human subjects emphasizes voluntariness and protection emphasizes voluntariness and protection

WMA Declaration of Helsinki Amended: 1975, 1983, 1989, 1996, 2000 Amended: 1975, 1983, 1989, 1996,

Three (U.S.) Revelations – 1960’s Sloan-Kettering researchers implanted cancer cells in skin of aged, debilitated and unknowing patients in Jewish Chronic Disease HospitalSloan-Kettering researchers implanted cancer cells in skin of aged, debilitated and unknowing patients in Jewish Chronic Disease Hospital NYU School of Medicine researchers infected profoundly retarded children (IQ<20) at Willowbrook State Hospital with hepatitis virus - ? Consent, coercionNYU School of Medicine researchers infected profoundly retarded children (IQ<20) at Willowbrook State Hospital with hepatitis virus - ? Consent, coercion Tuskegee RevelationsTuskegee Revelations

Tuskegee Syphilis Study US Public Health service: venereal disease sectionUS Public Health service: venereal disease section Goal: study of (untreated) syphilis, incidence and outcome in Macom County, AL.Goal: study of (untreated) syphilis, incidence and outcome in Macom County, AL. Subjects: 339 syphilitic A.A. men, 201 non-syphiliticSubjects: 339 syphilitic A.A. men, 201 non-syphilitic A.A. men A.A. men Pre-penicillin tx: arsenic and mercury.Pre-penicillin tx: arsenic and mercury. Jean Heller, “Syphilis victims in U.S. study went untreated for 40 years.” NYT 7/26/72 Jean Heller, “Syphilis victims in U.S. study went untreated for 40 years.” NYT 7/26/72

Tuskegee – Recruiting Free burial assistance ($50) & insurance – after autopsy (required)Free burial assistance ($50) & insurance – after autopsy (required) Free transportation to and from examsFree transportation to and from exams Free medicine and hot mealsFree medicine and hot meals

Tuskegee - Deceptions Dx: “Bad Blood”Dx: “Bad Blood” “therapeutic spinal taps”“therapeutic spinal taps” Prevented from receiving penicillin tx – (not allowed to be drafted)Prevented from receiving penicillin tx – (not allowed to be drafted)

Tuskegee Outcome NYT reported 7/26/72 – Ended studyNYT reported 7/26/72 – Ended study 74 men alive74 men alive 28 men died of syphilis, 100 died of relation complications, 40 wives were infected, 19 children were born with congenital syphilis28 men died of syphilis, 100 died of relation complications, 40 wives were infected, 19 children were born with congenital syphilis Presidential apology, 1997Presidential apology, 1997

Tuskegee - Outcomes The National Commission for Protection of Human SubjectsThe National Commission for Protection of Human Subjects Legacy of distrust and suspicionLegacy of distrust and suspicion

The Belmont Report – April 18, 1979 National Commission for Protection of Human Subjects of ResearchNational Commission for Protection of Human Subjects of Research 3 sections: Boundaries between practice and researchBoundaries between practice and research Basic ethical principles (3)Basic ethical principles (3) ApplicationsApplications

Belmont - Principles Autonomy – respect for personsAutonomy – respect for persons Beneficence – do good, minimize harmBeneficence – do good, minimize harm Justice – fairness, desertsJustice – fairness, deserts -special groups: children, prisoners, homeless or otherwise disadvantaged homeless or otherwise disadvantaged Nonmaleficence – added later

Belmont Applications Consent: information, comprehensive, voluntarinessConsent: information, comprehensive, voluntariness Risk/Benefit: To whom, for whomRisk/Benefit: To whom, for whom Selection of subjects – vulnerable personsSelection of subjects – vulnerable persons Belmont, revisited, JAMA 2006, 296: Belmont, revisited, JAMA 2006, 296:

Concluding Thoughts Different targets (of research efforts), same concernsDifferent targets (of research efforts), same concerns Short-term vs. long termShort-term vs. long term Individual vs. communityIndividual vs. community Truth vs. loyaltyTruth vs. loyalty Justice vs. mercyJustice vs. mercy