Ethical guidelines for human subject research arose out of abuse of power, unethical studies, and significant harm caused to individuals by participation, often involuntary and without consent, in research. This course will concentrate on the history and principles of ethical human subject research as set forth in the Belmont Report, the Office of Human Research Protections’ (OHRP) regulations, and the Helsinki Declaration. A selection of abuses in human subject research will be discussed. Several case studies will be presented dealing with social, behavioral, and educational research settings. The module will conclude with a brief quiz.
- Identify the three key Belmont Principles
- Describe the relationship between Belmont Principles and Office of Human Research Protections’ (OHRP) regulations
- Recognize the contribution of Helsinki Declaration
- Recognize the key instances of the abuse of human subjects
- Apply knowledge of ethical principles in social, behavioral and educational research settings
The Concentration Camps
The first guidelines for human subject research arose out of the Nuremberg Trials following World War II. During the war Nazi physicians and scientists used human subjects in their research, without consent and without considering the impact it would have on their subjects. Many of these studies were unnecessary, with questionable scientific merit, and designed to cause extreme pain and often death to the subjects. As expected, many subjects died as a result of the Nazi research atrocities. Many of the individuals who survived were traumatized and faced chronic health issues as a result of the experiments. The world followed the trial in horror, shocked at the depth of Nazi depravity. The result of the trial was the Nuremberg Code, ten concepts that serve as guidelines for ethical research with human subjects. (ref 1, ref 2)
The Nuremberg Code
From the Nuremberg Code, researchers were guided in five areas of human subjects’ research. First, Nuremberg stated that all subjects must give voluntary consent to participate in research and must be able to end participation in the experiment at any time. The subjects used by the Nazi’s were prisoners. They had no right to refuse and they often did not even know that they were research subjects.(ref 1, ref 2)
Second, Nuremberg held that experiments should yield useful results. Research should not be engaged in on a whim or to simply repeat what is already known. This is what is often referred to as scientific merit. The anticipated results of the study must contribute to science or benefit the field or discipline. (ref 1, ref 2)
Third, that the risk inherent in a study must never exceed the humanitarian importance of the study. When risk is involved in a study, it must be balanced by benefit. (ref 1, ref 2)
Fourth, experiments that are likely to result in suffering, injury, pain, or a priori death should not be conducted and research subjects should be protected from all of these; further, the researcher should terminate the experiment if continuation will cause suffering, injury, pain or death. The Nazis killed numerous prisoners during experiments, and caused others significant pain and harm. (ref 1, ref 2)
Fifth, experiments must be conducted only by scientifically qualified persons. (ref 1, ref 2)
Nuremberg enumerated the basic guidelines for ethical research. These areas would be repeatedly addressed as the scientific community sought to clarify what is ethical research.
In 1964, the World Medical Association gathered in Helsinki, Finland and authored a declaration to guide biomedical research. This declaration has been revised and updated several times (1975, 1983, 1989, 1996, 2000, 2008). (ref 3)
The basic principles of the Helsinki Declaration touch upon the following areas:
Research must conform to generally accepted scientific principles.
The design and performance of each experimental procedure should be outlined in an experimental protocol which should be reviewed by an independent committee.
Research should be conducted by scientifically qualified persons.
The importance of the objectives of the research is in proportion to the risk to the subject.
Concern for the interests of the subject is more important than the interests of science and society.
Subjects have a right to privacy.
Research results should be reported accurately.
The subjects must give informed consent.
When conducting research with individuals who are legally incompetent, consent must be given by the subject’s guardian.
It was the first revision of Helsinki that focused upon oversight of research by an independent committee—this introduced the concept of Institutional Review Boards. Much later revisions focused on distributing the risks and benefit of research among individuals equally as opposed to having disadvantaged persons bear the burden of research which will largely benefit the advantaged. (ref 3)
(45 CFR part 46) —
The Health and Human Service human subject protection regulations
The Health and Human Service human subject protection regulations (45 CFR part 46) were first published in 1974. In 1978, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research published the Belmont Report. (ref 4)
The National Research Act of 1974
After the ethical violations of the Tuskegee Syphilis Study came to light, there was a significant push to codify protections for human subjects in research. The National Research Act of 1974 (Public Law 93-348, Title II-Protection of Human Subjects of Biomedical and Behavioral Research) was the beginning of this codification. The National Research Act established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This Act really provided the impetus for the formalization of many aspects of what today falls under the umbrella of human research protections. The Commission was charged with identifying basic ethical principles for biomedical and behavioral research and developing guidelines for research to be conducted according to those ethical principles. This included delineating the boundaries between medical and behavioral research, developing risk/benefit criteria for determining the appropriateness of research involving human subjects, establishing guidelines for the selection of human subjects, and clarifying the nature and definition of informed consent. (ref 36)
The Belmont Report
The Belmont Report was an outgrowth of The National Research Act of 1974. The Belmont Report of 1978 outlines three key principles of ethical research: respect for persons, beneficence, and justice. These three principles are used by all IRBs to guide the decisions they make regarding research and should be used by all researchers in the creation of their research. (ref 4)
Respect for Persons
Respect for persons encompasses at least two parts. The first is that all individuals should be treated as autonomous agents, meaning he or she can deliberate about personal choices and act upon those deliberations. The second is that those individuals who are of diminished autonomy must be protected. These individuals may be of diminished autonomy because of illness, mental disability, cognitive deficits, or immaturity. (ref 4)
Four conditions flow from respect for persons: voluntary consent, informed consent, protection of privacy and confidentiality, and the right to withdraw without penalty from a study. (ref 4)
Individuals agree to participate in research freely and voluntarily, without undue coercion or pressure being put upon them to participate. Their consent must also be “informed,” they must know what the research is about; know what they are consenting to. Individuals who participate in research should expect that the information that they share in the context of research will be kept private, that their personal information will not be shared, and that they will be protected from damaging or embarrassing information that may be revealed during the context of research. Finally, any individual who agrees to participate in research can decide to discontinue participation at any time, for any reason, without giving a reason and without any penalty. (ref 4)
Beneficence asks us to examine the risks and the benefits of the study. First, the study should not do harm. Second, benefits must be maximized while harm is minimized. Third, the risks are justified by the benefits of the study. (ref 4)
This principle requires that the benefits and risks of research be evenly distributed through society. Specifically, this means that the disadvantaged must not bear the risks of research, while the advantaged reap the benefits—something that has happened all too often throughout the history of human subjects research since Nuremberg. (ref 4)
History of Human Subject Abuse
The Nazi-era Abuses
Protections for human subjects have arisen as a direct reaction to human subject abuses in research. During the Nazi era, experiments were performed on non-consenting subjects. These experiments included injecting dye into the eyes of subjects to see if they would change color; removal of bones, muscle and tissue without anesthesia; induction of head injuries; exposure to temperatures well below freezing; and the infecting of individuals with malaria. Many subjects died and most of those that survived suffered permanent disfigurement or disability as a result of the experiments. Certainly all of them suffered lasting trauma. (ref 1, ref 2)
The Milgram Experiment
Ironically, one of the most frequently discussed studies involving abuse of human subjects was designed to try to understand why individuals in the Nazi regime committed the atrocities they did. Milgram, at Yale University, studied obedience to authority by having research subjects supposedly administer what they thought were harmful (possibly lethal) doses to other subjects. The other subjects were actually co-experimenters, so no one was actually shocked, but still, the real subjects were left knowing that in many cases they would have administered high levels of shocks to others. (ref 5) (Video ref 11)
The Tuskegee Syphilis Study
A long-term study of the effects of untreated syphilis was conducted from 1932-1972. This study was backed by the U.S. Public Health Service. The research subjects were uneducated African-American sharecroppers from Alabama. At the outset of the study, there were no successful treatments for syphilis, but even after penicillin became the treatment of choice for the disease, these subjects were still simply watched to see what happened during the natural course of the disease. See The Tuskegee Timeline. (ref 6) (Video ref 12)
Zimbardo Prison Study
In 1973, Zimbardo, at Stanford University, conducted a study to see how otherwise ordinary individuals would conform to the roles of inmate and prison guard. Psychologically normal students were recruited for the roles of guards and prisoners. In a few days, the guards quickly conformed to their roles and began issuing random and demeaning orders, which the prisoners followed. By the sixth day, Zimbardo had to shut the study down as several “inmates” began showing signs of serious emotional disorder. See Thirty years later, Stanford Prison Experiment lives on. (ref 7)
Use of Prisoners in Research
From 1944-46 at the University of Chicago, malaria experiments were conducted on more than 400 Illinois prisoners. In 1945, a malaria experiment was conducted on 800 prisoners in Atlanta. In 1950, research at the University of Pennsylvania infected 200 women prisoners with viral hepatitis. 1951-1960, the University of Pennsylvania conducted psychopharmacological experiments on hundreds of prisoners while under contract to the U.S. Army. 1952-1974 University of Pennsylvania conducted dermatological experiments on hundreds of inmates. 1956, polio vaccine was tested on prisoners in Ohio. 1962-1980 drug testing conducted on prisoners by pharmaceutical companies. 1963-1973 testicular irradiation experiments conducted on prisoners in Oregon and Washington. See Human Experiments: A Chronology of Human Research. (ref 8)
San Antonio Contraception Study
In the late 1960s and early 1970s, 70 poor Mexican-American women who sought contraceptive services were either given oral contraceptives or a placebo. As predicted, those on the placebo became pregnant more often than those women taking oral contraceptives. (ref 8)
Tearoom Trade Study
In the early 1970s, Laud Humphries conducted a study of homosexual behavior for his doctoral dissertation. He first recorded the license plates of individuals that he had witnessed engaging in homosexual acts in men’s public bathrooms. He obtained names and addresses for these men and then went to their homes under the guise of being a health service interviewer and asked questions about their marital status and other personal information. See Laud Humphreys case at the University of Missouri-Columbia. (ref 9)
It is no coincidence that this Module has presented ethical guidelines for research as set out in the Nuremberg Code, the Helsinki Declaration, and the Belmont Report alongside some of the most famous ethical violations in modern history. The ethical guidelines that govern research were created as a reaction to ethical violations that have occurred and they continue to be shaped by our consideration of how to best protect human subjects in research.