I thank James Eisenach, MD for asking Edward Domino, MD1to provide us with a fascinating historic overview of the development of ketamine, a compound for which new uses are being found almost 50 yr after its introduction into US clinical practice. I commend Eisenach for asking Susan Palmer, MD,2to provide an ethical commentary about the experimentation on prisoners that was used to test the safety of phencyclidine and then ketamine. I agree with Palmer's conclusion that the results of Domino's experiments should be retained in the research literature. On the other hand, I respectfully disagree with her statements that respect for patient autonomy was not clearly defined in 1965 and that a clear understanding of a researcher's obligation to human subjects was achieved only after the development of federal regulations and their publication in the Code of Federal Regulations.

First, the Nuremberg Code, a response to unethical human experimentation on prisoners, clearly described informed consent and “free power of choice” in its first article in 1947.3Second, the Declaration of Helsinki, as adopted by the World Medical Association in June 1964, clearly described what is needed for informed consent in patients, such as prisoners, who are in a dependent relationship with the investigator.4Meanwhile, one anesthesiologist, Henry K. Beecher, MD, was at the forefront of identifying ethical problems with human experimentation; he reported his findings and opinions in several prominent journals, including this one.5,6Finally, although not relevant to Domino's experiments, the Belmont Report was published in 1979.*Therefore, I would argue that the definitions and obligations were available before the 1980s; the problem was that they were being ignored.

Indiana University School of Medicine, Indianapolis, Indiana. jfbutter@iupui.edu

Domino EF: Taming the ketamine tiger. Anesthesiology 2010; 113:678–86
Palmer SK: Preserving patients' health during WWII: Commentary. Anesthesiology 2010; 113:685–6
Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Washington, DC: US Government Printing Office, 1949, pp 181–2
Washington, DC
US Government Printing Office
Rickham PP: Human experimentation: Code of Ethics of the World Medical Association: Declaration of Helsinki. Br Med J 1964; 2:177
Beecher HK: Ethics and clinical research. N Engl J Med 1966; 274:1354–60
Beecher HK: More on patient consent. Anesthesiology 1968; 29:602–3
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. 1979