This chapter discusses the history of human experimentation, with special
attention to cases that have helped to shape ethical codes and policies. It
discusses important codes, such as the Nuremberg Code and the Decla-
ration of Helsinki, and it provides an overview of U.S. federal regulations.
The chapter also addresses some key concepts and principles in human
research, such as informed consent, risk/benefit ratios, minimal risk, re-
search versus therapy, and vulnerable populations.

The use of human subjects in research came into sharp focus during the
Nuremberg war crimes trials, when the world discovered the atrocities com-
mitted by Nazi doctors and scientists on tens of thousands of prisoners held in
concentration camps. While these tribunals were unfolding, the American
Medical Association (AMA) was developing a set of principles to be followed
in experiments using human subjects (Advisory Committee 1995). After the
tribunals concluded, in 1947 the research community adopted the world's first
international code for research on human subjects, the Nuremberg Code
(quoted in Advisory Committee 1995, p. 103). The code emphasizes the im-
portance of fully informed and voluntary consent of research subjects, mini-
mization of harms and risks to subjects, scientific validity of research design,
and the social value of the research. Since Nuremberg, there have also been
many documented cases of unethical or questionable research conducted in
the United States and other countries (Capron 1989; Beauchamp and Chil-
dress 1994; Advisory Council 1995). There have also been many ethical con-
troversies in human subjects research, such as the use of placebos in research,
the nature and practice of informed consent, and research on vulnerable pop-
ulations, such as children, prisoners, and the mentally ill (Shamoo and Irving
1993, Egilman et al. 1998 a, b). As a result, various federal agencies and scien-
tific and professional associations have developed regulations and codes gov-
erning human subjects research, and there has been a great deal of discussion
and debate about ethical standards that should govern the use of humans in re-
search (Levine 1988, Pence 1996). This chapter reviews these regulations after
providing a historical and philosophical perspective on these issues.

Alexander Morgan Capron (1989) has observed that “the darkest moments in
medical annals have involved abuses of human research subjects” (p. 127). A
brief survey of the history of human subjects research supports this view. Be-
fore the Scientific Revolution (circa 1500–1700 AD), medicine was an observa-
tional rather than an experimental science. Medical research was based on the

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