6 Historical aspects of research ethics and key ethical principles in research 

Research needs ethics

Between 1939 and 1945, at least seventy medical research projects involving cruel and often lethal experimentation on human subjects were conducted in Nazi concentration camps. More than seven thousand victims of such medical experiments have been documented. Victims include Jews, Poles, Roma (Gypsies), political prisoners, Soviet prisoners of war, homosexuals, and Catholic priests.

Nazi physicians organised trials of antibiotic and homoeopathic treatments in the concentration camps at Dachau and Ravensbrück. Healthy prisoners were given injections from the festering tissues of other inmates who had wound infections. In some people, small pieces of wood and glass were placed in open wounds, to mimic war injuries more realistically. The victims were then treated with homoeopathic preparations or various applications of sulfonamides; some received no therapy at all. Approximately one third of the victims died. All of these experiments followed a scientific logic that was outdated at the time, and which took no account whatsoever of the wellbeing of those involved in the research. The surviving victims had irreversible physical damage and severe psychological trauma (Roelcke, 2004).

Experiments in the context of aviation medicine were aimed at finding methods to help pilots survive after their planes had been hit at very high altitudes, or after an emergency landing at sea. The experiments, carried out in the Dachau concentration camp, focused on physiological questions, such as the effects on the human body of low pressure at high altitude, or of drinking salt water. For the high-altitude experiments, approximately 200 people were chosen from the camp prisoners, at least 70 of whom died during the experiments in a specially designed low-pressure cabin, or were killed afterwards to study the pathological changes in their brains. Judged strictly on scientific terms, the methods and results of some of these experiments were apparently innovative and useful. The United States Air Force continued some of this research after the war and published the results in cooperation with several German physicians involved in the original experiments.

The existing evidence illustrates an inherent logic of these research endeavors: the urge to establish new knowledge superseded any respect for the people who suffered in these experiments. Faced with the challenge of a given medical question, researchers sought opportunities to carry out the experiments required to solve it. It was in concentration camps, asylums, and hospitals in the occupied territories that they found these opportunities because existing legal regulations and sanctions did not apply there (Roelcke, 2004).

Tuskegee Syphilis Study

The United States Public Health Service (USPHS) Syphilis Study at Tuskegee was a clinical study conducted between 1932 and 1972. The study was intended to observe the natural history of untreated syphilis. As part of the study, researchers did not collect informed consent from participants and they did not offer treatment, even after it was widely available. The study ended in 1972 on the recommendation of an Ad Hoc Advisory Panel, convened by the Assistant Secretary for Health and Scientific Affairs, following the publication of news articles about the study. In 1997, President Clinton issued a formal Presidential Apology, in which he announced an investment to establish what would become The National Center for Bioethics in Research and Health Care at Tuskegee University. After the study, sweeping changes to standard research practices were made. Efforts to promote the highest ethical standards in research are ongoing today (Centers for Disease Control [CDC], 2022).

The Nuremberg Code

In response to the Nazi experiments, a trial of war criminals resulted. The main trial at Nuremberg after World War II was conducted by the International Military Tribunal. The tribunal was made up of judges from the four allied powers (the United States, Britain, France, and the former Soviet Union) and was charged with trying Germany’s major war criminals. After this first-of-its-kind international trial, the United States conducted 12 additional trials of representative Nazis from various sectors of the Third Reich, including law, finance, ministry, and manufacturing, before American Military Tribunals, also at Nuremberg. The first of these trials, the Doctors’ Trial , involved 23 defendants, all but 3 of whom were physicians accused of murder and torture in the conduct of medical experiments on concentration-camp inmates.

The resulting Nuremberg Code has the following principles:

1. The human subject’s voluntary consent is essential.
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
3. The experiment should be designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.
4. The experiment should be conducted to avoid all unnecessary physical and mental suffering and injury.
5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except in those experiments where the experimental physicians also serve as subjects.
6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
7. Proper preparations should be made, and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
9. During the experiment, the human subject should be able to end it if he has reached the physical or mental state where continuation of the experiment seems impossible.
10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill, and careful judgment required of him, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Australian context

In Australia, research practice is governed by the National Health and Medical Research Council’s (NHMRC) guidelines regarding ethical conduct in human research. The NHMRC guidelines outlines dos and don’ts when undertaking research activities.

Human research is research conducted with or about people, or their data or tissue. Human participation in research is therefore to be understood broadly, to include the involvement of human beings through:

• surveys, interviews or focus groups
• undergoing testing inclusive of psychological, physiological, or medical, or treatment
• being observed by researchers
• researchers having access to their personal documents or other materials
• the collection and use of their body organs, tissues, or fluids (e.g. skin, blood, urine, saliva, hair, bones, tumour and other biopsy specimens) or their exhaled breath
• access to their information (in individually identifiable, re-identifiable or nonidentifiable form) as part of an existing published or unpublished source or database.

The majority of human research conducted in Australia has been undertaken in a safe and ethically responsible manner. None the less, it is widely acknowledged that human research can involve significant potential risks, and these may occur unintentionally.

The development of the Nuremberg Code contributed to the World Medical Assembly (1964) developing the Helsinki Declaration. The premise of the declaration is to protect individuals and provides the foundations of the NHMRC guidelines, and the governance of research as a component of professional responsibility. The ethical conduct under the NHMRC guidelines is based on the assessment of research merit and integrity, justice, beneficence, and respect.

References

Centers for Disease Control and Prevention. (2022). The U.S. Public Health Service Syphilis Study at Tuskegee. https://www.cdc.gov/tuskegee/index.html

Roelcke, V. (2004). Nazi medicine and research on human beings. The Lancet, 364(Supp 1), 6-7.