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Belmont CITI
Belmont CITI
wording that became a classic defense for hazardous experimentation: "It is not cruel to inflict
on a few criminals sufferings which may benefit multitudes of innocent people through all
centuries." [Brady and Jonsen]. Both the ethics and regulation of human subjects research have
changed considerably since Celsus' time.
A brief synopsis of the history behind the current regulatory structure for research with human
subjects would read as follows:
"Highly publicized abuses in research led to congressional hearings in 1974. Congress
commissioned the preparation of a set of ethical principles, known as the Belmont Report. The
Federal Regulations for Protecting Research Subjects were subsequently revised and expanded,
based in large part on the Belmont Report. These ethical principles and regulations govern the
practice of research with human subjects in the United States."
Researchers in the social and behavioral sciences and humanities attest, correctly, that the
development of the regulations was driven by abuses in biomedical research. However, the
current regulations reflect and embody the ethical principles described in the Belmont Report
and these principles have broad applicability. For example, the principle of respect for persons
requires appropriate informed consent, and a portion of the regulations covers the informed
consent process.
This module will discuss examples of research abuses in biomedical research and examples of
research in the social and behavioral sciences that raised ethical issues. Some of these studies,
such as the Tuskegee study, the Milgram Obedience to Authority Study, and the Stanford Prison
Experiment will be familiar to many readers.
While it is possible to conduct ethical research without knowing the history described in this
module, knowing the history helps in understanding the regulations and their intended impact on
the practice of research with human subjects.
(For a description of the flexibility provided in the regulations that are useful for researchers in
the social and behavioral sciences in the humanities, such as exemptions and waivers of
documentation of consent, see the module in this series called The Regulations: An Overview.)
By the end of this module you will be able to:
• Describe major historical events that have influenced how research involving human
subjects is conducted today.
• Identify selected studies that have violated ethical standards.
• Describe the Belmont principles.
• Discuss the relationship between the Belmont principles and the federal regulations.
Beecher Article
In 1966 Dr. Henry K. Beecher, an anesthesiologist, wrote an article (Beecher HK. "Ethics and
Clinical Research" NEJM June 16, 1966) describing 22 examples of research studies with
controversial ethics. These studies had been conducted by reputable medical researchers and
published in major journals. Beecher wrote, "medicine is sound, and most progress is soundly
attained;" However, if unethical research is allowed to proceed it will "do great harm to
medicine." Beecher provides estimates of the number of unethical studies and concluded,
"unethical or questionably ethical procedures are not uncommon." [Beecher] Beecher's article
played an important role in heightening the awareness of researchers, the public, and the press to
the problem of unethical human subjects research. "Until this article we assumed that unethical
research could only occur in a depraved regime like the Nazis."- Robert J. Levine, MD (personal
communication).
The Public Health Service Syphilis Study (1932-1972)
One of the seminal events in the development of the
current regulatory environment was the Public Health
Service (PHS) Syphilis Study (1932 - 1972), frequently
referred to as the "Tuskeegee Syphilis Study" [see "Bad
Blood: The Tuskegee Syphilis Experiment", Revised
Edition by James H. Jones] . Initiated and funded by
the PHS, this study was designed as a natural study of
the course of syphilis in African-Americans. At the
time the study began there was no known safe and
effective treatment. Hundreds of men who did not
know they had syphilis and hundreds of men without
syphilis (serving as controls) were enrolled into the study. The men were recruited without their
fully informed consent. They were deliberately misinformed about the need for some of the
procedures. For example, spinal taps were described as necessary and special "free treatment"
for bad blood.
More importantly, even after penicillin was found to be a safe and effective treatment for
syphilis in the 1940s, the men with syphilis were denied antibiotics. In addition, the researchers
continued to protect the status of the study as a "natural history." To prevent the subjects from
being treated by the military or by local physicians, the investigators arranged with the local
draft board to prevent the men from being drafted, arranged with local physicians to withhold
treatment, and told the men that if they volunteered for the military, they would no longer
receive financial compensation for taking part in the study. The study continued to track these
men sporadically until 1972 when the first public accounts of the study appeared in the national
press. Not providing penicillin once it was deemed safe and effective may have been responsible
for 28 deaths, 100 cases of disability, and 19 cases of congenital syphilis. [Levine]
Ethical problems: lack of informed consent, deception, withholding information, withholding
available treatment, putting men and their families at risk, exploitation of a vulnerable group of
subjects who would not benefit from participation.
Recent Events
Death of a Normal Volunteer
On March 31, 1996, a 19-year-old Asian -American student at the University of Rochester
responded to an advertisement for study subjects to undergo bronchoscopy for the harvest of
alveolar macrophages. The bronchoscopy was difficult and required numerous doses of topical
lidocaine. The investigators repeatedly asked the subject if she wanted to continue and the
subject nodded her head "yes." The study was completed, but the subject returned to the hospital
in cardiac arrest from an overdose of lidocaine and died April 2, 1996. An investigation into this
death revealed that the protocol did not specify the number of lidocaine doses, that the doses
were not documented, that the subject was not observed after the bronchoscopy, and that the
concentrations of lidocaine were increased without IRB approval.
Death on Gene Transfer Trial
In the fall of 1999, 18-year-old Jesse Gelsinger died as a result of his participation in a gene
transfer trial. Jesse had a rare metabolic disorder that was being controlled by medication and a
strict diet. Shortly after the gene transfer attempt Jesse experienced multiple organ failure and
subsequently died. This case catapulted gene transfer research into the national news. Serious
concerns related to conflict of interest, data safety monitoring, and informed consent made the
Gelsinger case a contemporary illustration of continued doubts about the ethical integrity of
research with human subjects.
The purpose of this study was to learn more about how humans
respond when given instructions from people in positions of
authority. The researchers informed study volunteers that the
purpose of the research was to study learning and memory. Each
subject was told to teach a "student" and to punish the students'
errors by administering increasing levels of electric shock. The
"students" were confederates of the researcher and were never
actually harmed. The "students" pretended to be poor learners. They mimicked pain and even
unconsciousness as the subjects increased the levels of electric shock. Sixty-three percent of the
subjects administered what they thought were lethal shocks; some do so even after the "student"
claimed to have heart disease. Some of the subjects, after being "debriefed" from the study,
experienced serious emotional crises.
Ethical Problems: Deception, unanticipated psychological harms.
Summary
The Belmont Report and the federal regulations derived from the Report’s principles were
created in response to crises in biomedical research. Nonetheless, the principles focus attention
on the rights and welfare of all research subjects and provide tools for analysis and decision
making about critical ethical issues.