Nuremberg Doctors Trial Nazi physicians and administrators prosecuted by U.S. military tribunal for major war crimes, including medical experiments conducted on prisoners of war.

Significant violations of personal autonomy, malevolence, unjustifiable harm

Nuremberg Code Issued by the tribunal during the verdict, established first code of research ethics, 1947

Declaration of Helsinki World Medical Association code of ethics on human experimentation, 1964

Thalidomide anti-nausea drug stalled during FDA approval, birth defects mount

Risk unbalanced by benefit, informed consent, unproven drug safety and efficacy

Kefauver-Harris Amendments passed to strengthen FDA regulations (est. 1938) governing the drug development process, 1962

Beecher article, Ethics and Clinical Research examples of unethical biomedical research culled from recent literature, 1966.

Disregard for informed consent, unnecessary harm

Uniform Requirements for Manuscripts Submitted to Biomedical JournalsIssued by the International Committee of Medical Journal Editors, commonly referred to as the "Vancouver Group" 

Social and behavior research illuminates need for participant protections beyond the scope of biomedical studies:

Humphrey's Tearoom Trade, 1970

Stanford Prison Experiment, 1971

Milgram's "destructive obedience" Study, 1974

Deception, emotional and psychological harms, violations of privacy and confidentiality

American Psychological Association develops Research Principles, 1973, emphasizing the researcher's personal responsibility for ethical decision making

Tuskegee Syphilis Study NY Times article unveiled 40 year U.S. Public Health Service study in which poor, African-American men with syphilis were studied but left untreated, 1972.

Uninformed consent, injustice, risk to participants and family members

Led to formation of the National Research Act, 1974 and created initial guidelines for human subjects research in the Code of Federal Regulations

Resulted in The Belmont Report, by the Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979

Increase in production of legitimate but sophisticated medical devices such as the Dalkon Shield, Intraocular Lenses, and Cardiac Pacemakers drove Congress toward improved device regulations.

Unproven safety of marketed medical devices

Cooper Committee recommendations to regulate medical devices culminate in the Medical Device Amendments of 1976

Past research experiments exposed, lead to public mistrust:

Human Radiation Experiments 

Willowbrook State School Hepatitis Studies

Tudor "Monster" Study of Orphans

Unjustified physical and emotional harms, exploitation of vulnerable populations, absence of informed consent

President Clinton establishes the Advisory Committee on Human Radiation Experiments (1994) and the National Bioethics Advisory Commission (1995-2001)

Jesse Gelsinger dies in a gene therapy clinical trial in 1999; unethical research conduct uncovered

Conflict of interest, insufficient informed consent

Office for Human Research Protections issues Financial Conflict of Interest guidance, 2001

U.S. PHS Syphilis Study in Guatemala (1946-48) exposed

Absence of consent, injustice, risk to participants and family members, exploitation of vulnerable populations

President Obama establishes the Presidential Commission for the Study of Bioethical Issues in 2009 and requests investigation of Guatemala Syphilis Study, 2010