Development of Research Ethics

Our current perspectives on the ethics of human research were brought about through harsh reaction and adaptation. According to bioethicist Carol Levine, “the basic approach to the ethical conduct of research and approval of investigational drugs was born in scandal and reared in protectionism” (Marshall, 2002). The protection of the rights and welfare of research subjects has recently become a hot topic due to recent growth in both academic and commercial research. There has been much progress over the past decades in altering the culture of research to incorporate an improved ethical responsibility into protocol design and implementation. A variety of codes and reports together form the foundation for the ethical conduct of clinical research. Our current regulations are translated from these codes and used in practices, guidelines, and requirements for clinical research. The emergence of these ethical principles must be discussed within its historical context. To refrain from acknowledging its historical situation would be doing a great injustice to the many people who were harmed as a result of their unwitting participation in research trials (Perlman, 2004).

Ethics for human subject protection began with the ancient Hippocratic Oath, which stated the prime duty of a physician-to avoid bringing harm to the patient. Unfortunately, this once highly regarded oath has been neglected when pertaining to human experimentation, with most advances in protection spawning from responses to human abuse (Bhatt, 2010). Although the 1931 guidelines are claimed to be the first recorded ethical perspectives for human research, there existed a prior code, the Berlin Code 1900. The Berlin Code 1900 was instated by the Prussian Government, but was disregarded when the Empire gave way to the German Republic (Ghooi, 2011). Sometime afterwards in a Reich Circular on February 28, 1931 Weimar Government then issued a document entitled “Regulations on New Therapy and Human Experimentation”, also known as the 1931 guidelines (Annas, 1992). This government was then overthrown by Adolf Hitler and his Nazi party, whom completely ignored the existence of any ethical document, despite that it remained on statute books until 1948.

In August of 1947, in Nuremberg, Germany American judges sat in judgment of 23 Nazi doctors and scientist accused of conducting murderous and torturous human experiments in concentration camps. Some of the accused suggested that warrant for such horrific crimes, experiments and research, was the pursuit of scientific knowledge, the advancement of medical practice, and would help further understanding in order to develop procedures and cures to benefit humanity. This urged prominent members of the allied forces to draft the Nuremberg Code (1947), learning from the trials to provide a clear set of principles to inform future research and experimentation on human subjects. The guiding principles included: voluntary consent, informed consent, the right to withdraw, avoidance of harm and suffering, the expertise and qualification of the researcher, and the acknowledgement of the responsibilities of the researcher to the participant. These principles are replicated in contemporary codes and guidelines for human experiment ethics. (Kenny, 2008).

Following the atrocities of Nazi Germany and reactions to European colonialism, on December 10, 1948 the United Nations passed the Universal Declaration of Human Rghts. The universalist document defined the human rights of persons and violations to those rights. It contained important resolutions including the prohibition of slavery and torture, freedom of thought, opinion and expression, and a standard of living which includes access to medical care (Beyre, 2006). The Thalidomide tragedy that occurred in the late 1950’s triggered the drafting of the 1962 Kefauver-Harris Amendments, which reviewed the practices of pharmaceutical companies, requiring more intensive testing before releasing to the public. The 1962 Kefauver-Harris Amendments also made it mandatory to receive informed consent from patients that were to receive experimental drugs (Bhatt, 2010).

The first version of Declaration of Helsinki was adopted by the World Medical Assembly in 1964 in order to articulate general principles and specific guidelines for human subjects in medical research. It included 10 direct principles from the Nuremburg Code (Kenny, 20058). It stated that the well being of the individual takes precedence over science interests, experimental procedures must be detailed in protocol and reviewed by an ethical committee, legal documents of subject informed consent, and a detailed assessment of risk and benefits (Perlman, 2004). The Declaration of Helsinki is a current document that serves to take in account the quick evolving nature of science and research. It has been amended seven times since 1964, most recently at the General Assembly in October 2013(Declaration, 2014). This new version states for the first time that people who are injured during a medical trial must receive compensation and treatment. It also pushes for a higher degree of protection for vulnerable population groups (Arie, 2013).

In 1966, a Harvard anesthesiologist by the name of Henry Beecher, compiled an expose’ containing 22 examples of unethical experiments that were unknowingly published in reputable medical journals. His goal was to heighten awareness of the unethical activities being conducted in the U.S. It had substantial impact on the development of current regulations (Perlman, 2004).

This gruesome history of clinical research ethics left a stain on most people, causing suspicion of clinical trials and the motives of those who conduct them. One of the saddest examples of unethical human research is the Tuskegee syphilis study. In Alabama, between 1932 and 1972, a group of white researcher enrolled several uneducated African American farmers with syphilis into the Tuskegee study. The researchers told the men they would be receiving treatment for their illnesses, when in actuality the researchers observed the effect of the progression of untreated syphilis in their bodies. The participants were never told they had syphilis. In 1947 Penicillin was deemed the best medication for the treatment of syphilis. Instead of alerting the study participants, the researchers continued the trials and refused to treat their syphilis. The study finally concluded 25 years later due to an article published in the 1972 New York Times, which exposed the unethical atrocities. A congressional advisory panel deemed the Tuskegee Study “ethically unjustified” (Ryan, 2011). In 1974 The Nation Research Act was passed, authorizing the formation of the National Commission of the Protection for Human Subjects of Biomedical and Behavioral Research. The commission was set in place to conduct detailed examinations of all federally sponsored human subject research in the U.S. They developed philosophical and ethical principles that would be used to govern scientific research involving human test subjects (Perlman, 2004). In 1978 the commission began to draft the Belmont Report on the grounds that “although scientific research has produced substantial social benefits, it has also poses several troubling ethical question” (Bhatt, 2010). The report articulated three major core ethical principles: respect for persons, which included voluntary informed consent; beneficence, which included maximizing benefits and minimizing risks; and justice, which encompassed the idea of equitable selection of subjects (Perlman, 2004).

The International Conference on Harmonization published “Good Clinical Practice” in 1994, which is the current universal standard for ethics relating to human research subjects (Bhatt, 2010). All of these milestones and lessons in history structure the evolution of our current ethical perspectives. Even in the 21^st century we see the continuation of the evolution of research ethics with the evolution of technologies such as gene therapy, cloning, nanotechnology, internet research, artificial intelligence, chemical and biological terrorism, and space exploration.

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