Historical Background and General Information about Responsible Conduct of Research
Much of the following
material was adapted from several websites.
The University of Minnesota site was included and may be viewed at the
following URL http://www.research.umn.edu/first/index.html. Material has also been reproduced with
permission from the NIH course on research ethics which can be found at the
following URL http://researchethics.od.nih.gov/index_menu.html?nedid=browsing
Learning Objectives:
Describe some historical
issues in the responsible conduct of research.
Relate those issues to your own field.
Identify historical sources
for ethical values in research.
Consider how those values relate to your field and the type of research
that you conduct.
Discuss how ethical issues
in the responsible conduct of research can be resolved. Consider appeals to general principles,
case-based analysis, and other forms of public deliberation.
Ethical issues related to
responsible conduct of research have a long history. Reviewing historical cases and their resolution provides one
approach to dealing with current ethical issues. Ethical standards have changed over time, and past cases can show
the difference between the standards we now hold and those held by previous
researchers. Some issues persist and
some are new due to the changing nature of research. Current policies and laws have grown out of these past experiences. Most of the material available on these
issues relies on case based reasoning.
What you find are numerous cases and hypothetical examples. Going through those cases can sensitize the
reader to ethical issues and the variety of ways to resolve them.
Although not the first
example of harmful research on unwilling human participants, the experiments
conducted by the Nazi physicians during World War II were unprecedented in
their scope and the degree of harm and suffering to which human beings were
subjected. The "medical
experiments" were performed on thousands of concentration camp prisoners
and included such deadly studies as injecting people with gasoline and live viruses,
immersion in ice water, and forcing people to ingest poisons. In December 1946, 23 physicians and
administrators, many of them leading members of the German medical hierarchy,
were indicted before the war crimes tribunal at Nuremberg for their willing
participation in the systematic torture, mutilation, and killing of the
prisoners in experiments. Despite the
arguments of the German physicians that the experiments were medically
justified, the Nuremberg Military Tribunals condemned the experiments as
"crimes against humanity"; 16 of the 23 physicians were found guilty
and imprisoned, and 7 were sentenced to death.
In the August 1947 verdict, the judges included a section called
"Permissible Medical Experiments."
This section became known as the Nuremberg Code and has formed the basis
for ethics codes internationally
The predecessor agency to
the CDC funded a research project in which 400 African-American men with
syphilis were deceived into participating in a study of the natural history of
the disease. Subjects were offered
"treatment" for their disease, when in fact none was offered and the
only interventions were diagnostic and sometimes risky (spinal taps). During the course of the study, penicillin
was discovered, but withheld from the subjects until the time that the research
was stopped in 1973. This case was one
of the sentinel events that catalyzed the creation of federal regulations for
the protection of human research subjects.
The first accounts of this study appeared in the national press in
1972. The resulting public outrage led
to the appointment of an ad hoc advisory panel by the Department of Health,
Education and Welfare to review the study and give advice on how to assure that
such experiments would never again be conducted. Among the recommendations was the request that Congress establish
a "permanent body with the authority to regulate, at least, all
federally-supported research involving human subjects." In acknowledgement of its responsibility,
the government continues to compensate the surviving participants and the
families of deceased participants.
Reference: Allan Brandt,
"Racism and Research: The Case of the Tuskegee Syphilis
Study,"Hastings Center Report 1978; 8(6):21-29.
The Nuremberg Code served as
the first set of principles outlining professional ethics for medical
researchers. The ten points included
the statement that a "voluntary consent of the human subject is absolutely
essential" and further established that animal experimentation should
precede human experimentation; all unnecessary physical and mental suffering
and injury should be avoided; the degree of risk to the participants should
never exceed the "humanitarian importance of the problem" and should
be minimized through "proper preparations"; and that the participants
should always be at liberty to withdraw from the experiments. This set of points established the basic
principles that must be observed in order to satisfy moral, ethical, and legal
concepts in the conduct of human participant research. It has been the model for many professional
and governmental codes since the 1950s, and has, in effect, served as the first
international standard for the conduct of research.
The Declaration of Helsinki
is the code developed by the World Medical Association for the medical
community in response to Nuremberg. The
Declaration made an important distinction between therapeutic and
non-therapeutic research and, like the Nuremberg Code, it made informed consent
a central requirement for ethical research, but allowing for surrogate consent
when the research participant is incompetent, physically or mentally incapable
of giving consent, or a minor. However,
the Declaration states that research with these groups should only be conducted
when the research is necessary to promote the health of the population
represented, and when this research cannot be performed on legally competent
persons. It further states that when
the subject is legally incompetent, but able to give assent to decisions about
participation in research, then assent must be obtained in addition to the
consent of the legally authorized representative. The Declaration has been revised five times, most recently
October 2000, and includes in its 32 principles the statement that "the
benefits, risks, burdens and effectiveness of a new method should be tested
against those of the best current prophylactic, diagnostic, and therapeutic
methods." Although it says that
this does not exclude the use of placebo, or no treatment, in studies where no
proven prophylactic, diagnostic, or therapeutic method exists, this stipulation
is very controversial since some interpret it to mean that a placebo should
never be used whenever effective therapy is available, regardless of the
seriousness of the condition being studied.
The Declaration is important in the history of research ethics as the
first significant effort of the medical community to regulate itself.
In the 1950's and 1960's,
federal funding for biomedical research increased dramatically but at the same
time there was increasing public concern expressed about research reports such
as Tuskegee and other biomedical abuses.
In response to this public outcry, Congress established the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral
Research in 1974 to make recommendations for the conduct of research involving
humans. The primary task of the
National Commission was to identify the ethical principles that would guide all
research involving humans. In 1979, the
National Commission wrote The Belmont Report - Ethical Principles and
Guidelines for the Protection of Human Subjects which is the cornerstone of
ethical principles upon which the federal regulations for the protection of
human research participants are based.
By 1981, the Department of Health and Human Services and the Food and
Drug Administration published regulations based on the Belmont Principles. Ten years later, in 1991, 17 federal
departments and agencies agreed to adopt the basic human participant
protections, generally referred to as the Common Rule (Title 45 Code of Federal
Regulations Part 46).
In 1979, the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral
Research wrote their report, Ethical Principles and Guidelines for the
Protection of Human Subjects of Research, commonly called the Belmont
Report. In this report the Commission
identified and described the basic ethical principles that underlie
research. The Commission considered the
boundaries between biomedical and behavioral research and the accepted and
routine practice of medicine in order to "know what activities ought to
undergo review for the protection of human subjects of research". The report also describes the assessment of
risk-benefit criteria in the determination of appropriateness of research on
participants, appropriate guidelines for this assessment, and the nature and
definition of informed consent. The
three fundamental ethical principles that guide the ethical conduct of research
involving human participants are:
The principle of respect for
persons incorporates at least two ethical convictions.
1. Individuals should be
treated as autonomous agents.
"An autonomous person
is an individual capable of deliberation about personal goals and of acting
under such deliberation. To respect
autonomy is to give weight to the autonomous persons' considered opinions and
choices while refraining from obstructing their actions..." (Belmont
Report).
Prospective research
participants must be given the information they need to determine whether or
not to participate in a study. There
should be no pressure to participate and ample time to decide. Respect for persons demands that
participants enter into the research voluntarily and with adequate information,
this is called informed consent.
2. Persons with diminished
autonomy may need additional protections.
Special provision may need
to be made when comprehension is severely limited or when a class of
participants is considered incapable of informed decision-making (such as with
children, people with severe developmental disorders or dementias). Even for these persons, however, respect
requires giving them the opportunity to choose, to the extent they are able,
whether or not to participate in research activities. In some cases, respect for persons may require seeking the
permission of other parties, such as a parent or legal guardian. The judgment that one lacks autonomy should
be periodically reevaluated and may vary in different situations.
Human participants are
treated in an ethical manner not only by respecting their decision and
protecting them from harm, but also by making efforts to secure their
well-being. The principle of
beneficence obligates the researcher to maximize possible benefits and minimize
possible harm. The problem posed by
these imperatives is to decide when it is justifiable to seek certain benefits
despite the involved harms or risks.
Balancing risks and benefits is an important consideration. The goal of much research is societal
benefit, however, in the interest of securing societal benefits; no individual
shall be intentionally injured.
The ethical considerations
of risks versus benefits leads to the question of justice. This principle requires that we treat
participants fairly, and involves questions such as who should bear the risks
of research, and who should receive its benefits? Justice is a difficult and complex ethical issue. Attempts must be made at all times in the
study to distribute the risks and benefits fairly and without bias. Also, unless there is clear justification,
research should not involve persons from groups that are unlikely to benefit from
subsequent applications of the research.
The concept of justice may be questioned when deciding who will be given
an opportunity to participate, who will be excluded, and the reason for
exclusion. When making such decisions,
the researcher must ask: Are some classes of persons being selected simply
because of their availability, their compromised position, or their
vulnerability - rather than for reasons directly related to the problem being
studied?
We should always be careful
about evaluating the past with standards of the present. Nevertheless, issues of fraud, plagiarism,
and falsification of research findings are not new. There are a number of rather old historical cases where sometimes
famous investigators engaged in questionable practices. Some of the more illustrious cases have been
recorded in Broad and Wade’s book, Betayers of the Truth.
The reported assortment of
Mendel’s colored peas exactly matched his predictions based on theory. Unfortunately, such precision would not be
seen in natural assortment, so the conclusion is that Mendel “cooked” or
‘trimmed” his data.
Reference: W. Broad, N.
Wade, "Deceit in History," in Betrayers of the Truth (NY: Simon and
Schuster, 1982).
Stanley Milgram was a social
science researcher interested in studying the personal behavior of
individuals. But to do so, he employed
deception as a research method. His studies
included observing the behavior of men in gay bath houses, then following them
home and posing as a door-to-door survey researcher so he could ask them about
the intimate details of their sex lives; and placing volunteers in situations
where they were required to be obedient and then asked to carry out actions
that would cause harm to others, including delivering electric shocks.
Reference: Arthur Miller,
The Obedience Experiments: A Case Study of Controversy in Social Science. (NY:
Praeger, 1986).
Our most recent concerns
about scientific integrity arose in the 1980s when the US government became
involved. The following brief history
is taken from the Office of Research Integrity (ORI) website which can be found
at the following URL: http://ori.dhhs.gov/html/about/historical.asp
Scientific misconduct became
a public issue in the United States in 1981 when then Representative Albert
Gore, Jr., chairman of the Investigations and Oversight Subcommittee of the
House Science and Technology Committee, held the first hearing on the emerging
problem. The hearing was prompted by the public disclosure of scientific
misconduct cases at four major research centers in 1980. Some twelve cases of
scientific misconduct were disclosed in this country between 1974-1981.
Congressional attention to scientific misconduct was maintained throughout the
1980s by additional allegations of scientific misconduct and reports that the National
Institutes of Health (NIH), universities, and other research institutions were
inadequately responding to those allegations.
Congress took action in 1985
by passing the Health Research Extension Act.
The Act, in part, added Section 493 to the Public Health Service (PHS)
Act. Section 493 required the Secretary of Health and Human Services to issue a
regulation requiring applicant or awardee institutions to establish "an
administrative process to review reports of scientific fraud" and "report
to the Secretary any investigation of alleged scientific fraud which appears
substantial." The Section also required the Director, NIH, to establish a
process for receiving and responding to reports from institutions. This
legislation complemented existing authority under which the PHS pursued
scientific misconduct in the 1970s and early 1980s. Guidelines were published
in the NIH Guide to Grants and Contracts in July, 1986; the Final Rule,
"Responsibilities of Awardee and Applicant Institutions for Dealing With
and Reporting Possible Misconduct in Science", was published in the
Federal Register on August 8, 1989. This regulation is codified at 42 CFR Part
50, Subpart A.
Before 1986, reports of
scientific misconduct were received by funding institutes within PHS agencies.
In 1986, the NIH assigned responsibility for receiving and responding to
reports of scientific misconduct to its Institutional Liaison Office. This was
the first step taken to create a central locus of responsibility for scientific
misconduct within the Department of Health and Human Services.
In March 1989, the PHS
created the Office of Scientific Integrity (OSI) in the Office of the Director,
NIH, and the Office of Scientific Integrity Review (OSIR) in the Office of the
Assistant Secretary for Health (OASH). The sole purpose of these offices was to
deal with scientific misconduct; the creation of OSIR also began the process of
removing responsibility for scientific misconduct from the funding agencies. In
May, 1992, OSI and OSIR were consolidated into the Office of Research Integrity
(ORI) in the OASH. Later that year, HHS established a hearing opportunity for
all scientists formally charged with research misconduct.
In June 1993, the process of
removing responsibility for handling allegations of scientific misconduct from
the funding agencies was completed when President Clinton signed the NIH
Revitalization Act of 1993. This Act established the ORI as an independent
entity within the Department of Health and Human Services (HHS). Organizationally,
ORI is located within the Office of the Secretary of Health and Human Services
in the Office of Public Health and Science which is headed by the Assistant
Secretary for Health.
In October 1999, HHS
announced several changes designed to improve its processes for responding to
allegations of research misconduct and promoting research integrity. The final definition was published in the
Federal Register on December 6, 2000.
First, HHS will adopt the proposed government-wide definition of
research misconduct developed by the National Science and Technology Council
after it is finalized by the Office of Science and Technology Policy. The proposed definition was published in the
Federal Register on October 13, 1999.
Second, extramural institutions and intramural research programs have
the primary responsibility for responding to allegations of scientific
misconduct. The Office of Inspector
General, HHS, rather than ORI conducts any fact-finding required by the federal
government. ORI continues to conduct
oversight reviews of all investigations.
Third, the Assistant Secretary for Health, upon recommendations from
ORI, makes the final decisions regarding scientific misconduct and
administrative actions, subject to appeal.
Fourth, the HHS Departmental Appeals Board continues to hear appeals,
but the hearing panels include two scientists rather than one or none. Fifth, all extramural research institutions
are required to provide training in the responsible conduct of research to all
research staff who have direct and substantive involvement in proposing,
performing, reviewing, or reporting research, or who receive research training,
support by PHS funds or who otherwise work on PHS-supported research projects
even if the individual does not receive PHS support. The PHS Policy on
Instruction in the Responsible Conduct of Research was published n the Federal
Register on December 1, 2000 and suspended on February 20, 2001 pending review
of the substance of the policy and whether the document should have been issued
as a regulation rather than a policy.
Sixth, HHS published a notice of proposed rulemaking on the protection
of whistleblowers in the Federal Register on November 28, 2000; comments were
due by January 29, 2001.
At the present time, the
mandate for instruction on responsible conduct of research is pending final
approval. The research community
anticipates that this mandate for education in RCR will be implemented by the
end of 2002.
As a postdoctoral fellow,
Margot O’Toole blew the whistle on what she claimed was the falsification of
data in a laboratory run by David Baltimore.
The scientist charged with fraud was Teresa Iminshi-Kari, and the story
of the alleged falsification, O’Toole’s whistleblowing, and the level of
Baltimore’s responsibility for the research and its subsequent publication
offer valuable lessons for contemporary science.
Reference: Daniel Kevles,
The Baltimore Case, (NY: WW Norton, 1998).
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