Recognition of the need for guidelines dealing with human subjects in research emerged following the Nuremberg trials, where the medical experimentation abuses of World War II Nazi doctors came to public attention. This led to the creation of the Nuremberg Code in 1945, the first legal attempt to deal with ethical issues of modern research. As biomedical research efforts expanded the international need for a more specific code of ethics was formulated in the 1964 Declaration of Helsinki.
In the United States, by 1953 the National Institutes of Health required that all proposed clinical research projects at its center in Bethesda obtain approval from a protection of human subjects review panel. In 1966, the United States Public Health Service issued its first set of regulations extending this review requirement to all "extramural" research supported by the agency. These rules were further revised in 1971 and 1974 and led to the establishment of institutional review boards (IRBs) at hundreds of institutions receiving federal funding for research.
During this period revelations of human subjects abuse in the U.S. culminated in the 1972 public disclosure of the 30-year government supported Tuskegee Syphilis Study, in which 300 black rural men were left untreated for diagnosed syphilis even after effective antibiotics became available. This prompted Public Law 93-348 calling for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. In 1979 the Commission published recommendations, known as the Belmont Report, that served as the basis for revised federal regulations published in the Federal Register in 1979 and subsequently revised several times resulting in the current Code of Federal Regulations Title 45-Part 46 Protection of Human Subjects (45 CFR 46) effective as of 1991.
The Belmont Report laid out three general ethical principles that should govern human subjects research:
- Beneficence: To maximize benefits for science, humanity, and research participants and to avoid or minimize risk or harm.
- Respect: To protect the autonomy and privacy rights of participants.
- Justice: To ensure the fair distribution among persons and groups of the costs and benefits of research.
- DHHS (Effective August 1991). Code of Federal Regulations Title 45 Part 46-Protection of Human Subjects (45 CFR 46).
- Greenwald, R. A., Ryan, M. K., & Mulvihill, J. E. (Eds.) (1982). Human subjects research: A handbook for institutional review boards. New York: Plenum Press.
- Seiber, J. E. (1992). Planning ethically responsible research: A guide for students and internal review boards. Newbury Park, CA: Sage Publications.