Key Events in Ethical Research

Before the mid 1970s, policy regarding the ethics of research was practically non-existent. The
National Research Act (Pub. L. 93-348) of 1974, and the resulting activities of the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral Research,
resulted in the ethical principles established within the Belmont Report. Over time, policy
regarding the ethics of research involving human participants has continued to evolve across
multiple agencies as various professional organizations and government bodies continue to
provide guidance and regulation.
Capella has an Institutional Review Board (IRB) that reviews all research to be conducted by
Capella learners, faculty, and staff to ensure that it meets the ethical standards set forth in
research policies such as the Belmont Report and the Code of Federal Regulations.
The following information describes some key events in research that have contributed to the
implementation of these research policies and the development of institutional review boards to
ensure the protection and ethical treatment of human subjects.

World War II Concentration Camp Experiments and Nuremberg Code 1947.

The atrocities committed by Nazi doctors in the name of medical experimentation, as revealed
during the Nuremberg war crimes trials, raised international consciousness about the need for an
international code of ethics for medical research. At Auschwitz, Dachau, Ravensbrck,
Buchenwald, and other Nazi-run camps, thousands of men, women and children were subjected
to heinous experiments. The experiments frequently led to severe disability, horrible
disfigurement, and death. Thousands of prisoners were used as experimental subjects in
sterilization experiments. Thousands more were victims of Nazi researchers who induced
hypothermia and extreme dehydration, secretly administered poisons, infected subjects with
malaria, inflicted chemical burns, and purposefully infected wounds.
The international code of medical ethics drafted by an international panel in response to the
atrocities committed in the Nazi camps, originally called Permissible Medical Experiment,
became known as the Nuremberg Code. The first of the 10 principles that comprise the
Nuremberg Code begins: The voluntary consent of the human subject is absolutely essential.
Although it did not carry the force of law, the Nuremberg Code was the first international
agreement advocating voluntary participation and informed consent. Its principles served as a
model for the continued development of guidelines for research involving human subjects.

Photograph: The exhibit entitled 'Unscrupulous and Scrupulous' at the Medical History Museum
on April 29, 2003 in Berlin, questions the legitimacy of medical experiments by Nazi doctors.
Experts believe that there were 8,000 to 10,000 victims of the Nazi medical experiments (Photo
by Kurt Vinion/Getty Images).

Non-Approved Thalidomide and Kefauver-Harris Amendments 1962.

The Kefauver-Harris amendment to the 1938 Food and Drug Act was the first U.S. law requiring
informed consent. Passage of the amendment can be directly attributed to public anger over the
thalidomide disaster, in which thousands of people were prescribed the drug during the 1950s to
control nausea during pregnancy. Most patients did not realize that the drug had not been
approved by the FDA. More than 12,000 babies were born with severe deformities in
consequence.
In 1962, the U.S. Senate passed the amendments. In addition to requiring informed consent, the
amendments strengthened federal oversight of drug testing, requiring manufacturers to prove the
effectiveness and safety of their drugs before bringing them to market.

Declaration of Helsinki.
In 1964, the World Medical Association established recommendations and guiding principles for
biomedical research involving human subjects. The Declaration was revised in 1975, 1983, 1989
and 1996; and is the basis for good clinical practices used today.
Issues addressed in the Declaration of Helsinki include:

Research with humans should be based on results from laboratory and animal
experimentation.

Research protocols should be reviewed by an independent committee prior to initiation.

Informed consent from research participants is necessary.

Research should be conducted by medically/scientifically qualified individuals.

Risks should not exceed benefits.

Ongoing Experimentation and Common Rule, Institutional Review Boards.

A number of experiments during the 1960s and 1970s raised concerns about the issues of
consent, deception, and confidentiality for human research subjects. Among the best known are
the Milgram Experiment at Yale (electric shock treatment) of 1961, Humphreys Tea Trade (male
sexual encounters) of 1970, and the Zimbardo Guard Study (simulated prison experiment among
Stanford college students) of 1971.
In response to these concerns and a growing awareness of the need to establish clear, ethical
guidelines, the Department of Health and Human Services (DHHS) and the Food and Drug
Administration (FDA) issued regulations in 1981 based on the Belmont Report.
DHHS issued Code of Federal Regulations (CFR) Title 45 (public welfare), Part 46 (protection
of human subjects). The FDA issued CFR Title 21 (food and drugs), Parts 50 (protection of
human subjects) and 56 (Institutional Review Boards).
Today, most federal departments and agencies have adopted the core DHHS regulations as the
Common Rule." The main elements of the Common Rule include requirements:

To ensure compliance by research institutions.

For researchers obtaining and documenting informed consent.

Providing protections for certain vulnerable research subjectspregnant women,

prisoners, and children.

Establishing Institutional Review Board (IRB) membership, function, operations, review

of research, and record keeping requirements.

An Institutional Review Board (IRB) is a group of organizational and community representatives

required by federal law to review the ethical issues in all proposed research that is federally
funded, involves human subjects, or has any potential for harm to subjects. Federal regulations
require that every institution that seeks federal funding for biomedical or behavioral research on
human subjects have an IRB to review research proposals.
Illustration: A diagram describing the Milgram Experiment. The subject of the experiment, is
ordered to give, what they believe to be, painful electric shocks to another participant, who is
actually an actor, for each wrong answer as punishment.

Tuskegee Syphilis Study.

On July 25, 1972, the Washington Evening Star newspaper ran this headline on its front page:
"Syphilis Patients Died Untreated." With those words, one of America's most notorious medical
studies, the Tuskegee Syphilis Study, became public after 40 years of silence.

In 1932, the United States Public Health Service and the Tuskegee Institute began a study in
Macon County, Alabama. The subjects were 600 mostly poor and illiterate African-American
men, 399 with syphilis and 201 without. None of the infected men were told they had the
disease. Instead, they were told that they would receive treatment for "bad blood.
Treatments for syphilis at the time were largely ineffectual and dangerous. By 1947, penicillin
had become the standard, effective treatment. However, none of the studys participants received
penicillin, nor information about it. Instead, Tuskegee researchers deliberately withheld
treatment in order to study the progression of the disease.
The study went on for 40 years until the story broke and made headlines in 1972. By then, of the
399 infected participants, 28 had died of syphilis and 100 from medical complications related to
the disease, 40 wives of participants had been infected, and 19 children had been born infected.
Although not publicized, the Tuskegee Syphilis Study was not a secret; several researchers had
published papers and data during the decades of the study.
In 1973, largely as a result of the outcry over the experiment, Congress passed legislation
creating the National Commission for the Protection of Human Subjects of Biomedical and
Behavioral Research. Several years later, the Commission published Ethical Principles and
Guidelines for the Protection of Human Subjects of Research, commonly known as The
Belmont Report.
In 1997, President Clinton offered an official apology on behalf of the United States government
to the study subjects and their families.
Photograph: Participants in the Tuskegee Syphilis Study (Photo source: NARA's Southeast
Region, Atlanta).
Image: Macon County Health Department physicians, participating in the Tuskegee Experiment,
sent the following letter to over 400 patients. The letter states that this is the last chance
participants have for special free treatment. The special treatment was actually a diagnostic
lumbar puncture.
Macon County Health Department.
Alabama State Board of Health and U.S. Public Health Service Cooperating with Tuskegee
Institute.
Dear Sir:
Some time ago you were given a thorough examination and since that time we hope you have
gotten a great deal of treatment for bad blood. You will now be given your last chance to get a
second examination. This examination is a very special one and after it is finished you will be
given a special treatment if it is believed you are in a condition to stand it.

If you want this special examination and treatment you must meet the nurse at _____ on
_____at_____. She will bring you to the Tuskegee Institute Hospital for this free treatment. We
will be very busy when these examinations and treatments are being given, and will have lots of
people to wait on. You will remember that you had to wait for some time when you had your last
good examination, and we wish to let you know that because we expect to be so busy it may be
necessary for you to remain in the hospital over one night. If this is necessary you will be
furnished your meals and a bed, as well the examination and treatment without cost.
REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT. BE
SURE TO MEET THE NURSE.
Macon County Health Department.
(Image source: NARA's Southeast Region, Atlanta).
Image: This is a section of the draft report on the Tuskegee Syphilis Study, dated October 8,
1949. It notes that 140 participants died in the first 16 years of the study. The report also states
that autopsies were performed on 98 of the deceased.
An important phase of the study has been the performance of autopsies on the individuals who
have died. Through 1948, 140 of the number included in the original population have died, and
of these 98 have been autopsied. Of those on who autopsies have not been performed, proof of
death has been established by death certificate or by information furnished by relatives or friends
of the deceased. Because of the relatively non-migratory nature of the group, it is reasonably
certain that there have been no other deaths than the 140 recorded. No analysis of autopsy data
will be attempted in this report...
(Photo source: NARA's Southeast Region, Atlanta).

Belmont Report Principles

The Belmont Report established boundaries between research and practice, and detailed three
basic principles to guide ethical research involving human subjects. These principles have since
informed many other sets of guidelines and codes of ethics.

Principal of Respect: The research intent and protocol must recognize the autonomy of
humans and require clear and informed consent from human subjects.

Principal of Beneficence: The research must be shown to be beneficial and reflect the
Hippocratic idea of do no harm.

Principle of Justice: The potential benefits to some must be balanced against the risks to
the research subjects.