1. voluntary informed consent to participate is absolutely essential (1, 9);

2. "avoid all unnecessary physical and mental suffering and injury" (4, 5, 7, 8, 10);

3. "risk to be taken should never exceed" the expected benefits of the study (6, 2, 3)

Declaration of Helsinki (1964 - 2000)

The World Medical Association codified the principles they value in the Helsinki Declaration of 1964. The 1964 original document lists 5 basic principles (section I), 2 principles for clinical research (section II) and 4 principles for non-clinical biomedical research (section III). These 11 principles (or standards) updates the ones listed in the Nuremberg Code. The Declaration was further revised four times in 1975, 1983, 1989 and 1996. The fifth revision in 2000 was the most controversial due to disagreements on international standards for the use of placebo (article 29) and the issue of assurance of access to best proven intervention arising from the study (article 30).

The requirements or standards referred to in the Nuremberg Code and the Declaration of Helsinki as principles are understood today as rules (or guidelines). This distinction between ethical standards/requirements/rules and principles became clearer in the Belmont Report of 1979.

Rules and principles

One way to make sense of the distinction between 'requirements/rules/standards' and 'principles' is to distinguish between moral rules, ethical principles, moral theory and judgments about a specific actions.

In simple terms, judgments are based on rules, rules on principles, and principles on moral theory (e.g. utility-based, duty-based, or virtue-based theories of moral obligations). Moral reasoning can be understood as proceeding in this hierarchical order of abstraction.

Belmont Report (1979)

After the signing of the U.S. National Research Act of 1974, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was convened and they issued the Belmont Report in 1978 which was published in the Federal Register in 1979. The Report is the first document to list what we understand today as ethical principles for research. The mandate of the Commission is "to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles" (from the summary of The Belmont Report).

Three principles were identified in the Belmont Report:

1. Respect for persons - this principle "demands that subjects enter into the research voluntarily and with adequate information"
2. Beneficence - obligation to "(1) do not harm and (2) maximize possible benefits and minimize possible harms"
3. Justice - to distribute burdens and benefits of research in a just way is formulated as "(1) to each person an equal share, (2) to each person according to individual need, (3) to each person according to individual effort, (4) to each person according to societal contribution, and (5) to each person according to merit"

The Report mentions historical instances of unethical research that should now be prevented such as

during the 19th and early 20th centuries the burdens of serving as research subjects fell largely upon poor ward patients, while the benefits of improved medical care flowed primarily to private patients. Subsequently, the exploitation of unwilling prisoners as research subjects in Nazi concentration camps was condemned as a particularly flagrant injustice. In this country, in the 1940's, the Tuskegee syphilis study used disadvantaged, rural black men to study the untreated course of a disease that is by no means confined to that population. These subjects were deprived of demonstrably effective treatment in order not to interrupt the project, long after such treatment became generally available.

The basic principles identified in the Belmont Report are needed as bases for justifying specific moral rules and guidelines that will be developed later in national and international instruments regulating research. These principles were also used in developing guidelines in clinical ethics and bioethics, popularized in the well-known book by J. Childress and T. Beauchamp (1979). A fifth edition came out in 2001.

CIOMS Guidelines (2002)

The Council for International Organizations of Medical Sciences (CIOMS) issued their International Ethical Guidelines for Biomedical Research Involving Human Subjects in 1982, 1993 and 2002. The latest version adopts the 3 principles contained in the Belmont Report as general ethical principles (2002, p. 17) that ground the 21 guidelines that follow. 

The debate on the importance of principles

Some (e.g., Clouser & Gert 1990) are critical of the use of general principles while others (Beauchamp 1995; Gillon 2003) defend it.  Clouser and Gert argued that principles, e.g. those identified by Beauchamp and Childress (1994), do not adequately determine action nor provide practical guidance because they are so general and vague. Moral rules are more specific. The label "principles" does not make research ethics documents, e.g. the Nuremberg Code or Declaration of Helsinki, susceptible to such criticism because the principles contained there are more like rules. It does apply to principles in post-Belmont Report documents but not to requirements that apply those principles, e.g. the requirement 'to obtain informed consent' that apply the principle of respect for persons.

The debate between proponents of Kohlberg's stages of moral development and Gilligan's ethics of care also asks this question about the importance of principles. Kohlberg's highest stage of moral development is one that is based on universal ethical principles, e.g. justice. Gilligan's criticizes the prominence of principles as specific only to men (Gilligan 1977). She argued that women focus on response or "caring" rather than on universal principles of morality. Therefore, we cannot assume that everyone (men and women alike) will rely on universal principles of morality as their most developed state of moral behavior, as Kohlberg claims.

Despite empirical studies pointing to the personal motivations for moral actions, some authors (Cropanzano, Goldman & Folger 2003) defend the role of principles or standards of right and wrong. 

Still others (Emanuel, Wendler, Grady 2000) prefer more specific ethical requirements "that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies."

References:

Clouser, K. D., & Gert, B. (1990). A critique of principlism. Journal of Medicine and Philosophy, 15(2), 219-236. http://dx.doi.org/10.1093/jmp/15.2.219

Cropanzano, R., Goldman, B., & Folger, R. (2003). Deontic justice: the role of moral principles in workplace fairness. Journal of Organizational Behavior, 24(8), 1019-1024. http://dx.doi.org/10.1002/job.228

Emanuel EJ, Wendler D, Grady C. What Makes Clinical Research Ethical?. JAMA. 2000;283(20):2701-2711. http://dx.doi.org/10.1001/jama.283.20.2701

Gilligan, C. (1977). In a Different Voice: Women's Conceptions of Self and of Morality. Harvard Educational Review, 47(4), 481-517. http://dx.doi.org/10.17763/haer.47.4.g6167429416hg5l0

Gillon, R. (2003). Ethics needs principles—four can encompass the rest—and respect for autonomy should be “first among equals”. Journal of Medical Ethics, 29(5), 307-312. http://dx.doi.org/10.1136/jme.29.5.307