Historical Incidents Related to Human Subjects Protections

  • Hippocrates (400 BCE) and Oath: “Do no harm …“
  • Individual responsibility of researcher – two millennia
  • Walter Reed (1900) Consent forms in Spanish and English: malaria research
  • Nuremburg Code (1946) Twenty-six medical researchers from holocaust tried for unethical conduct toward “vulnerable” population. Rules and principles developed.
  • Wichita, Kansas (1950’s) Secret audio taping of jury deliberations for legal research. University of Chicago challenged in Congress by James Eastland (of Ruleville, MS).
  • NIH Clinical Research Center at Bethesda (1960) sets up internal review committee and many other research hospitals voluntarily follow suit.
  • Thalidomide, an experimental drug in Europe was allowed for use in the United States with waiver of clinical trials by FDA(1962). Those receiving drug were not warned that it was still ‘experimental’.
  • Sloan-Kettering conducts research using “live” cancer cells on humans (1963). Subjects were told that research was testing their resistance to cancer, but not that they would receive live cancer cells. One MD tried to stop it and took Sloan-Kettering to court where defendants were convicted of assault & battery. Malpractice was also shown.
  • James Shannon (1964) at NIH reviews protections for all human subjects in NIH funded research. Agency begins taking a leading role in protecting human subjects.
  • Stanley Milgram (1965) conducted famous research on ‘obedience’, using deception as part of the design. Despite debriefing, a strong outcry from other professionals.
  • Henry K. Beecher (1966) reviewed biomedical research literature and showed that human subjects protections were violated in over 500 papers. His analysis was published in the New England Journal of Medicine and in two books (see References).
  • PHS research on untreated syphilis (1972) was initiated in the Alabama in the 1930’s. The longitudinal project continued for years, and even after the use of penicillin, 300+ African American subjects were left untreated (and uninformed). Senator Edward Kennedy challenged this research in Congress.
  • The National Research Act (1974) was passed by Congress. IRB’s were established and a National Commission for Protection of Human Subjects was established.
  • The Belmont Report (1978) was published, based on the Presidentially commissioned work of MD Psychologists, Lawyers, and Biomedical and Behavioral Ethicists. This beautifully reasoned and written document proposed to go beyond “rules and regulations” to propose principles to use in judgments about protecting human subjects.
    • Respect for Persons
    • Beneficence
    • Justice
  • Vulnerable subject samples (1980-present). More recently, guidelines and regulations have been developed to guide researchers on protecting rights of “vulnerable” subjects including economically disadvantaged, minority, prisoners, mentally incompetent, pregnant mothers, fetuses, and even fetal tissues. While these issues are important, the volume of effort by Congress and federal agencies clearly illustrate political implications, rather than the moral or ethical considerations which are more important.
  • Recent Controversies and Issues
    • Undue Inducement
    • Duke University
    • Third Party Informed Consent (Oral History and the Human Genome Project)
    • Johns Hopkins “An artist’s reply to just criticisms …”. Dimitri Shostakovitch.

The Nuremburg Code

Following the atrocities in medical research during the Holocaust of WWII, this code was developed to provide specific rules intended to prevent future abuse of research subjects. The Nuremburg Code differs from the later Belmont Report in that the later developed general principles and provided far more depth of understanding for research ethics.

  1. The voluntary consent of the human subject is absolutely 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 so 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 so conducted as 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, perhaps, 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 course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seemed to him to be 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.