The Nuremberg Code was created after World War II, following the Nuremberg Trials, with the goal of protecting human rights and patients in clinical research. During World War II, extensive human experimentation was conducted by the Nazis (National Socialists) in Germany. These experimentations were exposed during the Nuremberg Trials of 1947 and resulted in a code of ethics, which set “standards to which physicians must conform when carrying out experiments on human subjects.” The code of ethics was called for, taking into account that several of the accused in the “Doctors’ Trials” presented arguments that their medical experimentations differed little from those conducted by others in the United States and elsewhere, prior to World War II.
One such example brought up by the trial defendants was the Stateville Penitentiary malaria experiments that took place in Illinois in the United States. The nominated medical adviser to the Nuremberg Trials, Andrew Ivy, had firsthand knowledge of these experiments. The defendants furthermore argued that there was no law differentiating between what is and is not allowed, and therefore they had committed no legal crime. Based on this, six main points defining what is and is not legitimate medical research were presented to the Counsel for War Crimes by Leo Alexander. The results of the trial itself reiterated these points and included the addition of four more points in the verdict in a section titled “Permissible Medical Experimentation.”
Key roles in the analysis of the ideas and shaping of medical research ethics, born from the trials, were played by American neuropsychiatrist Leo Alexander, German psychiatrist Werner Leibbrand, and American physiologist/medical historian Andrew Ivy. Ivy is recorded as stating during the trials that there is “no justification in killing five people in order to save the lives of five hundred” and citing the Hippocratic moral maxim in that “what refers to the Hippocratic oath is that he must have respect for life and the human rights of his experimental patient.” Together, the 10 points became the basis of the 10 principles of the Nuremberg Code, although no specific findings from the trials were included.
The principles called for informed consent, absence of coercion, well-thought-out and planned scientific experimentation, and benefits to the participants in the clinical research. In general, it was argued that the ethics of human experimentation should be in conformation with the ethics of the medical profession and the Hippocratic oath, but that more was necessary to protect human subjects participating in clinical research, hence bringing forth the Nuremberg Code of ethics.
The 10 principles of the Nuremberg Code were adapted and expanded upon in the Declaration of Helsinki. While the Nuremberg Code protects the human rights of clinical research subjects, the Declaration of Helsinki focuses on the obligations of the physicians to the participants. Probably the most important of these is that participation by the human subject in experimentation must be by voluntary consent (changed in the Declaration of Helsinki to also include consent by the legal guardian when the subject is legally incapacitated). The Nuremberg Code was pivotal in changing what constitutes good and ethical conduct of clinical research.
The Helsinki Report
Also known as the Declaration of Helsinki, the Helsinki Report is a cornerstone document on the ethics of human clinical research, developed by the World Medical Association (WMA) in 1964, with seven revisions, the latest and only official version of which can be found at the WMA’s website (http://www.wma.net/en/20activities/10ethics/10helsinki/index.html). It is one of the first major efforts of the medical community to regulate itself, and it built upon the previously developed Nuremberg Code of 1947. Major revisions were made in 1975, 2000, and most recently in 2013. The first revision was the Tokyo (1975) revision, the second was the Venice (1983), the third was the Hong Kong (1989), and the fourth was the Somerset West, South Africa, (1996) revision.
The first 700-word Declaration of Helsinki developed and corroborated the 10 principles that were first stated in the Nuremberg Code with the Declaration of Geneva, which was more geared toward the ethical duties of physicians.
The first major revision in 1975 doubled the length of the original document, ensuring that concern for the subject (the patient volunteer) must always come before the interests of science and of society. This revision also included the introduction of the requirement of an independent oversight committee for the clinical research project. This concept was adapted in the United States as the Institutional Review Board (IRB), and in other countries with similar equivalent ethics review committees.
Calls for the Edinburgh (2000) revision of the Helsinki Report
Having been developed out of controversy, the fifth revision in 2000, known as the Edinburgh (2000) revision, also resulted, and to some extent remains, in considerable controversy. This revision required monitoring of clinical scientific research to ensure and reinforce ethical standards, and was in part spurred by a seminal paper published by Peter Lurie and Sidney M. Wolfe in 1997, which called for the discontinuation of human immunodeficiency virus (HIV) trials in developing countries, citing discriminations in change of study design between Thailand and Africa. Importantly, the proclamation of the Tokyo (1975) version remained in paragraph 5 of the Introduction in the Edinburgh (2000) version, stating that “In medical research on human subjects, considerations related to the well-being of the human subject should take preference over the interests of science and society.” Much of the controversy, however, arose around the area of the ethical requirements of placebo-controlled trials, described below.
Major changes in the 2000 revision
It is of note that a major change in the 2000 version was in the organization of the original four versions, which were grouped under three headings: I. Basis Principles, II. Clinical Research Combined With Professional Care, and III. Non-Therapeutic Clinical Research. The separate headings distinguished between clinical research that was purely scientific without therapeutic value or that was of therapeutic value to the subject, but was removed in the Edinburgh (2000) revision. Instead, the utility of healthy volunteers replaces Non-therapeutic Clinical Research. In paragraph 16, the participation of healthy volunteers as research subjects is described as being permissible, and in paragraph 18, they are described as an important group for prior weighing of the risks and burdens against the importance of research. While the revision is supported on the one hand as having a much more logical organization and sequence of reasoning, it is criticized as being of concern in that there is no section that distinctly discusses research involving no benefit to the participants, except perhaps that such groups are often paid for their participation in research.
Perhaps the most controversial parts of the fifth revision of the Declaration of Helsinki are paragraphs 29 and 30, which fall under the heading Additional Principles for Medical Research Combined With Medical Care. These are described separately below. Some of the other successes and sources of debate are described here and begin with the Introduction. Today, discussions still arise, perhaps purposely, on the dilemma described in the Introduction of the Edinburgh (2000) version of the declaration, which argues on both sides—for the challenge of current medical practices and against the use of people as a means to an end. The Introduction ends with no real conclusion, and therefore perhaps this unwritten subtlety calls for the continued debate contained in the words of the 1975 version that recommendations “should be kept under review in the future” removed in this 2000 revision.
The beginning of paragraph 1 repeated the words of older versions, but added a second sentence stating, “Medical research involving human subjects includes research on identifiable human material or identifiable data.” This sentence brings about the question of research involving anonymous human research, for example, that which utilizes de-identified clinical samples. This concern was discussed by Povl Riis in his paper Perspectives on the Fifth Revised Declaration of Helsinki. In this same paper, Riis raises discussion on paragraph 6. Again, in paragraph 6, it is the second sentence that was added, which is the subject. Here, the ethical onus is placed on physicians to challenge their practices through research for greater efficacy, efficiency, accessibility, and quality, but it does not elaborate on the definitions of these