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OCR for page 43
The Ethics of Human Subjects Research
This Committee was asked to determine whether the AAL thyroid function study "was
conducted in accordance with generally accepted guidelines for use of human participants in
medical experimentation," and whether participants had been notified about possible risks. This
aspect of the ComTnittee's charge proved to be particularly challenging. Determining whether
the }~3] research was conducted according to generally accepted guidelines of the 1950s means
first determining what research ethics guidelines should be applied to judge human subjects
research that took place at that time in history, and second, applying those general guidelines
to the unique circumstances of the }~31 study. To do this with any accuracy, it is necessary to
consider the history and evolution of medical ethics and the ethics of research with human
subjects. We must understand where we were at the tune the research was conducted in
comparison to where we are today, and face the problems inherent in second-guessing the past.
To determine whether the AAL thyroid function research followed "generally accepted
guidelines," the Committee had to consider both principles and practices. If only the principles
of research ethics were considered, then virtually all research would be unethical, as principles
can only rarely be employed in a manner that raises no questions at all. Thus it seems reasonable
to conclude that considering only principles would hold researchers to an unfairly high standard.
If, however, only the actual practices of the time were considered, a different unfairness would
result. Requiring researchers only to do what other researchers do would render principles
meaningless and change impossible. Thus, considering only practices would justify all research,
and such a standard would be unfair to subjects.
The challenge, then, when assessing research with human subjects whether the research
is in the past or the present is to examine both principles and practices to determine and apply
"generally accepted guidelines." This is what the Committee sought to do. In the process, we
realized that the evolution of principles and practices of human subjects research has been more
gradual than swift, and composed of small and spreading changes rather than of dramatic
paradigm shifts. As important as our examination of the }~3} study is, it is even more important
to recognize that education about the ethics of human subjects research is a continuing necessity
today.
43
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44
The ALL Thyroid Function Study
BACKGROUND
To understand the concept of informed consent and the legal/moral underpinnings of
human subject experimentation as related to the AAL study, it is necessary to understand how
these underpinnings developed. Medical treatment and human subjects research share two
ethical mandates: to avoid harm and to respect the patient's self-determination (autonomy).
Thus, research must be designed to produce meaningful! knowledge with minimal risk. In
addition, subjects must make free and informed decisions about whether to participate. These
issues are discussed at length in A History and Theory of Informed Consent (Faden and
Beauchamp, with King, 1986), which is drawn upon heavily here.
The ethical mandates underlying the conduct of research using human subjects are
derived from several sources, including:
· the ancient and traditional duty of physicians to benefit their patients, or at least do them
no harm;)
· the Kantian philosophical view of human beings as "ends in themselves," never to be
used merely as means to ends, or for the advantage of others;2
· the political and legal concept of autonomy or self-determination that requires consent
to any bodily intrusion;3 and
· the requirements of good scientific method in designing and conducting experiments,
including: minimization of risk.4
These ethical concepts are often translated into three basic principles that provide a
framework for the moral conduct of human subjects research:
· The principle of "autonomy," or personal self-governance, "by adequate understanding
while remaining free from controlling interferences by others and from personal limitations that
prevent choice" (Faden et al., 1986, p. 81. In order for a research subject to make an
autonomous choice, the autonomy of the subject must be respected, which includes providing
sufficient information for the subject to make an autonomous and informed decision.
According to Faden et al. (1986, p. 10), " [A] celebrated principle in the history of medical codes
of ethics is the maxim primum non nocere 'above all, do no harm.' Recent scholarship has shown that
in the Hippocratic writings the more precise formulation is 'help, or at least do no harm,' thus demanding
the provision of benefit beyond mere avoidance of harm."
According to Faden et al. (1986, p. 81. "As expressed in Kantian philosophy, autonomous
persons are ends in themselves, determining their own destiny, and are not to be treated merely as
means to the ends of others. Thus, the burden of moral justification rests on those who would restrict
or prevent a person's exercise of autonomy."
3Faden et al., 1986, p. I, p. 7-9, 26-30.
4Federal Common Rule § 1 1 1 (a)( 11-~21. See Appendix E.
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The Ethics of Human Subjects Research
.
45
The principle of "beneficence," which is concerned with the intent and capacity of
science and medicine to avoid harm and provide benefit; in the case of research, this requires
careful weighing of potential harms against potential benefits.
· The principle of "justice," or treatment according to what is fair, due, or owed, which
includes avoiding unfairly burdening subjects or communities of subjects in relation to benefits.
For every research project involving human subjects, two basic inquiries are necessary.
One inquiry must examine the necessity of the research, the expected results, the risk-benefit
balance, and minimization of risks. The other inquiry must examine the fairness of subject
selection, adequacy of information given to prospective subjects, and voluntariness of subjects'
consent to participation. In very general terms, the first inquiry addresses the research's potential
for harming subjects and the second addresses the research's potential for wronging them. Also
speaking very generally, the first inquiry is beneficence based, whereas the second is concerned
with autonomy and justice.
Although these two sets of research components are considerably interdependent, it is
nonetheless possible to commit harms without wrongs-for example, an unexpected injury can
occur in an apparently risk-free experiment before it can be halted. It is also possible to commit
wrongs without harms, such as when a minimally risky experiment causes no injuries to
subjects, but where the subject selection process or the informed consent process is defective.
Harming without wronging may be easier to grasp than wronging without harming. In
biomedical settings, the focus on avoiding physical harms can tend to overwhelm other
considerations. However, especially in research, according participants full respect and dignity
and treating them with fairness and justice is of great importance, independent of physical harm.
In some contexts, treating study participants with less than full respect may be more damaging
than physical harm' and the effects may be longer lasting. The Committee' therefore' gave equal
consideration to the potential for harms and for wrongs.
Evolution of Ethical Standards
Although use of human subjects in medical experiments is an ancient practice, use of
human subjects in scientifically rigorous research only became established in the United States
shortly before the outbreak of World War Il. Before the postwar promulgation of the Nuremberg
Code, some attention was paid to the ethical issues raised by medical research with human
subjects (Faden et al., 1986, pp. 151-153). Early moral and legal concerns about human subjects
research focused more on controlling research risks than on enabling autonomous choice by
research subjects. It took the Nuremberg Trials, however, to bring human subjects research to
public consciousness and to launch the development and Implementation of ethical standards for
such research.
Although the evolution of standards for the use of human subjects in research does not
start with the Nuremberg Code, the Code was a watershed event in bioethics that helped
determine the development of contemporary standards. It is essential to understand that the
Nuremberg Code was intended, and was understood at the tine, to be an expression of existing
and universal moral principles governing research with human subjects (Advisory Committee
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46
The ALL Thyroid Function Stucly
on Human Radiation Experiments, 1995). Therefore, despite the fact that the Code had not
existed as such at the tune the Nazi experiments were conducted, the Nuremberg Military
Tribunal could apply it to condemn the experiments.
The Nuremberg Code
The Nuremberg Military Tribunal was formed to examine the legal and ethical aspects
of human experiments carried out by Nazi physicians before and during World War II. As a
result of its investigation, on August 19, 1947, the Tribunal issued a lO-point list of principles
delimiting morally and legally permissible human experimentation (see Box 3.~. The Code
focuses primarily, but not exclusively, on the subject's free and infonned consent. It requires
subjects to have decision-making capacity and to be able to consent freely, without "the
intervention of any element of force, fraud, deceit, duress, over-reach~ng, or other ulterior form
of constraint or coercion." Subjects must be given information about the nature, methods,
duration, and purpose of the experunent, and about all reasonably anticipated risks, hanns,
inconveniences, and health effects, in order to enable them to choose with understanding about
their participation. Subjects must be able to withdraw from participation at any tune. In
addition, Me Code prescribes that research design should ensure that the experunent is capable
of yielding worthwhile results, that the degree of risk does not exceed the value of the results,
that all risks to human research subjects are minunized, and that research is conducted according
to appropriately high scientific standards.
After the Code
The Code was well promulgated and widely discussed, begs ng in the late 1940s and
early l950s. In 1946, while the Nuremberg Trials were going on, the Judicial Council of the
American Medical Association (AMA) set out three requirements for human subjects research:
(1) voluntary consent of the subject, (2) prior animal experimentation to determine risk' and (3)
proper medical management of the experiment.s The February 27, 1953' issue of Science led
with a set of short papers from a 1951 symposium under Me title "The Problem of
These requirements constituted the Judicial Council's application of the AMA's Principles of Medical
Ethics lo human experimentation. The requirements were issued in response lo Dr. Andrew C. Tvy's
report on the Nuremberg Trials. Dr. Ivy served as the AMA's official consultant to the Nuremberg
prosecutors and played a significant role in the development of the Nuremberg Code (Advisory
Committee on Human Radiation Experiments, 1995~. They were published in the Journal of the American
Medical Association (lAMA) on December IS, 1946, and reiterated in 1958 when JAMA published the
AMA's 1957 Principles of Medical Ethics and Opinions and Reports of the Judicial Council.
OCR for page 47
The Ethics of Human Subjects Research
47
OCR for page 48
48
The CAL Thyroid Function Study
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Experimentation on Human Beings." These papers included an extensive discussion of the
Nuremberg Code, as well as a discussion of rights of military personnel regarding medical
treatment and research. The Code's general principles were adopted specifically by both the
AMA and the Department of Defense.
But in the postwar period, dissemination of and implementation of the Nuremberg Code
was, to say the least, uneven. In 1953, the Department of Defense formally adopted the Code
in guidelines addressing the use of human subjects for research related to atomic, biological, and
chemical warfare, but the document was classified Top Secret because of government sensitivity
about these military issues (see Appendix D). This is the earliest instance in which a federal
agency that sponsored human experiments adopted the Nuremberg Code, although related
discussions were ongoing in other agencies in the same era (Advisory Committee on Human
Radiation Effects, 1995~. (The policy remained classified until 1975.) The Atomic Energy
Commission discussed informed consent issues in a series of letters dating back to 1947 and
developed subject consent requirements for the use of radioisotopes it supplied to medical
researchers, but did not systematically promulgate or enforce them (Advisory Committee on
Human Radiation Experiments, 1995~. Many medical researchers apparently believed that
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The Ethics of Human Subjects Research
49
because the Nazi experiments were so obviously flawed, both ethically and scientifically, the
Nuremberg Code was intended only to apply to ill-intentioned human subjects research-"It was
a good code for barbarians but an unnecessary code for ordinary ohYsicianst' (Advisory
~ hi.
Committee on Human Radiation Experiments, 1995~.
At the same time, worldwide attention was being paid to the language of the Code itself,
and new guidelines were being drafted to provide better guidance for physicians and researchers
than the Code was thought to offer. Professional societies and associations, world bodies, and
governmental entities all began to develop guidelines. One set of guidelines became especially
influential. This was the Declaration of Helsinki, first drafted in 1961 by the World Medical
Association. Like the Nuremberg Code, the Declaration of Helsinki focused on consent as a
central requirement (Faden et al., 1986' pp. 156-157).
In 1953, the National Institutes of Health's new Clinical Center developed and
implemented a rigorous in-house policy requiring informed consent and peer review of risk-
bearing research (Faden et al., 1986, pp. 201-2021. And in 1959, Henry Beecher published the
first of his influential exposes of research practices with human subjects, the monograph
"Experimentation in Man" (Faden et al., 1986, p. 157~. Thus, in the early to mid-1950s the
Principles governing research with human subjects were firmly in place, but their implementation
In practice was incomplete and even contused. Clear moves toward systematic reform of
research practice did not come until the 1960s and 1970s.
--a or-
~. ~
~- - ~
. , . . , , ~ ~ · _-
The Evolution of Modern Federal Regulations
In the United States, modern guidelines for human subjects research began to take final
form in 1974. In 1971 the U.S. Department of Health, Education, and Welfare (DHEW) issued
guidelines for the conduct of social and behavioral research that in 1974 were codified into
federal regulations governing human subjects research in institutions receiving DHEW funds.
Also, legislation (P.~. 93-34S, National Research Act) created the National Commission for the
Protection of Human Subjects of Biomedical and Behavioral Research, which in 1979 authored
what became know as the Belmont Report (National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research, 1979~.
The Belmont Report sets forth the same three basic ethical principles governing human
subjects research that were outlined early in this chapter and that underlie the Nuremberg Code:
respect for persons, beneficence, and justice. The report points out that respect for persons
demands the informed and voluntary consent of the subjects; beneficence demands an assessment
of the relative probability and magnitude of risks to subjects against benefits expected from the
results; and justice demands equitable selection of subjects and equitable distribution of the
research's benefits and burdens between research subjects and the population at large.
The 1974 DHEW regulations6 grew into a federal policy for the protection of human
These regulations establish a system of Institutional Review Boards (IRBs) charged to review and
approve of human subjects research, and set forth approval criteria. These criteria include the following:
that risks to subjects be minimized; that risks to subjects be reasonable in relation to anticipated benefits
(continued)
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so
The ALL Thyroid Function Study
subjects known as the "Common Rule." It is applicable to all human subjects research taking
place under the auspices of any federal department or agency, including the Department of
Defense. The federal Common Rule was published in the Federal Register on June I8, 1991
(56 F.R. 28003-280321. (The Department of Defense's version of the Common Rule appears
in its regulations, Code of Federal Regulations, volume 32, part 219.) The Common Rule
provides much more detailed and specific guidance to human subjects researchers and their
institutions than was available to the AAL physicians. The regulations develop the principles of
the Nuremberg Code and provide guidelines for their implementation, which the Code lacked.
In 1993, there was much more information available to assist researchers and their institutions
in implementing appropriate protection for human subjects than was available to the AAL
researchers in the 19SOs, but the basic underlying principles were the same then as now.
The Nuremberg Code as Applied to AAL Research in 1955-1957
During the mid-1950s, the application of ethical standards for the conduct of human
subjects research was uneven in the federal government and guidelines for Implementation were
inconsistent. Many researchers, policymakers, and governmental and military personnel may
have mistakenly considered the Nuremberg Code to apply only to overtly hazardous research or
experiments lacking scientifically reasonable goals. As related earlier, Dr. RodahI, when asked
directly over the telephone during the public hearing in Fairbanks if he had any guidelines
similar to the Nuremberg Code for obtaining informed consent, told the Committee that he did
not, but that he had approvals from his supervisors and if there was anything wrong with the
research it would not have been approved, and he would not have been allowed to publish his
study results.
However, the Nuremberg Code itself, in its own language and as set forth in the medical
and scientific literature of the times, is unqualified in its application to "the human subject."
The Code was developed to be an expression of universal moral principles governing research
with human subjects it was considered to represent current research ethics, acceptable and
accepted at the time rather than new terrain. Therefore, in the Committee's, opinion the
standards outlined in the Code did apply to human subjects research in the 19SOs, including
research conducted under military auspices. Regardless of misconceptions about the applicability
or scope of the Nuremberg Code, and regardless of the failure of the Air Force to implement
to the subjects or from the resulting knowledge; that subject selection be equitable; and that the subjects'
informed consent be obtained. Informed consent requirements are set out, including a list of required
elements of disclosure. The regulations are supplemented by publications from the National Institutes
of Health Office for Protection from Research Risks, which include interpretive guidelines for use by
[RBs in the conduct of their work. These guidelines address a variety of questions in detail, including
subject selection, research with special populations, and refinements of informed consent.
Current AMA (1992) policy on clinical investigation similarly contains requirements for informed
consent and "rigorous scientific standards" for research, but with considerably less detail than the federal
regulations.
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The Ethics of Human Subjects Research
51
or disseminate its classified Code-based policy, in the Committee's opinion, the standards of the
Code applied to--the ethical conduct of the AAL research physicians and scientists, and to their
superiors, at the tune the research took place.
As should be clear from the Committee's description of the AAL research and the
process of our inquiry, the l}3} research was far from egregious. Subjects, both Alaska Natives
and Air Force personnel, were given some information and an attempt at obtaining informed
consent was made. The radioactive tracer was administered in doses believed to be harmless,
and the purpose of the research was not to determine the effects of radiation in the human
body7. Thus, by comparison with some of the Cold War research examined by the Advisory
Committee on Human Radiation Experiments (e.g., plutonium injections and active deception
of patient-subjects), it might seem overly scrupulous to be concerned with a close analysis of the
|~3i study.
Nonetheless, there are three reasons for careful examination of the }~3} study according
to the terms of the Nuremberg Code. First, the subjects were normal healthy volunteers and
there was no indication that the researchers expected the study to result in unprovement of the
subjects' health.9 Second, radioisotopes are potentially harmful substances, and thus the }~3
fit should be noted that the AAL thyroid function study was only one of many studies using }~3
conducted from the 1940s to 1960s. The report Human Radiation Experiments Associated with the U. S.
Department of Energy and Its Predecessors (1995), prepared as part of DOE's effort to document human
radiation experiments, includes at least 60 studies involving li3} in diagnostic, therapeutic, and research
settings.
The Advisory Committee on Human Radiation Experiments was appointed by President Clinton in
1994 to conduct an extensive inquiry into the history of government-sponsored human radiation
experiments and intentional environmental releases of radiation that occurred between 1944 and 1974.
The I,000-page final report found that the government sponsored approximately 4,000 radiation
experiments involving tens of thousands of individuals, many of whom had no knowledge that they were
participating in radiation research. The committee recommended that the government apologize to people
who received no direct medical benefit from participation in research and provide financial compensation
for those who suffered physical injury as a result of participation. The committee recommended that
subjects in three particular studies (about 30 people) receive financial compensation for being subjected
to dangerous experiments without their knowledge, and gave guidelines that might lead to compensation
to others. The committee rejected proposals that the government notifier all known participants or their
families or provide wide-scale medical follow-up.
committee's report and recommendations, and issued an apology to all those who were used as subjects
in government-sponsored radiation experiments, and their families. He also established a new body, the
National Bioethics Advisory Committee, to develop new policies to guide research in human biology and
. . .
review ongoing government researc :~.
In October 1995, President Clinton accepted the
9The Advisory Committee on Human Radiation Experiments (1995), in discussing the use of
healthy subjects in medical research, noted: "The use of patients in medical research appeared in a
different historical context from that of healthy subjects. From the perspective of the medical profession,
the age-old tradition of the doctor-patient relationship provided a justification for research with the
potential to benefit patients, but not, of course, for healthy subjects who were not under medical care."
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The AA1: Thyroid Function Study
research was not without theoretical risk. And third, the overwhelming majority of the subjects
were Alaska Natives, who may have represented a population of convenience and whose
language and cultural differences from the physician-researchers certainly affected the consent
process and their role as subjects. It is to elucidate these reasons, and to explore their
importance, that we embark upon an application of the terms of the Nuremberg Code to the Ii3i
research.
Several aspects of the informed consents relationship between researchers and subjects
must be examined according to the terms of the Nuremberg Code: (1) subjects' legal capacity
and freedom to choose under the circumstances; (2) researchers, disclosure of information about
the experiment, and subjects' knowledge and comprehension of this information; and (3) the duty
and responsibility of researchers to obtain consent. Although the Code is general and offers
no guidance as to how the requirements should be fulfilled, its language is explicit. The
following discussion looks at the principal terms of the Code as relevant to the AAL research.
i. "bathe person involved should have legal capacity to give consent, [and] should be
so situated as to be able to exercise free power of choice, without the intervention of any element
offorce, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion. "
The conduct of the AAL thyroid function study raises a variety of concerns related to
consent and free power of choice. For instance, although the researchers excluded young
children from the study, at least seven of the Alaska Native subjects were under 2l, the age of
majority in the Territory of Alaska at the time (Compiled Laws of Alaska, §20-1-1, 1949).
Minors' unless "emancipated,' lack the legal capacity to give consent. Minors become legally
emancipated by participating in certain adult activities such as marriage or military service.
Some of these minor subjects of the AAL research were emancipated by marriage; others were
not. Parental consent was not sought for any minors, to the Committee's knowledge. The
researchers apparently instructed elders and interpreters that they needed "adult or near-adult"
volunteers, and then simply recorded the ages of subjects brought to them. The inclusion of
minor subjects in research without parental consent is a violation of ethics and law, both for the
period of the experiments and in 1993. There were three minor subjects among the U.S. Air
Force participants; however, since military service is an emancipating condition' there was no
legal conflict in those cases.
In addition, the Committee has significant concerns about whether the Alaska Native
subjects were "so situated as to be able to exercise free power of choice" under the
circumstances. These concerns relate to the use of village authority figures to identify
~°AIthough the term "informed consent" did not come into use until 1957 (Faden et al., 1986, p.
125), the elements that define consent in the Nuremberg Code correspond well to the Committee's
contemporary concept of "informed consent," and so that term is used here for convenience.
'~There are many modern lists of elements of informed consent to research that are equivalent.
For example, a moral definition is: An intentional authorization given to a researcher by a subject who
has substantial understanding, and is not substantially controlled by others (Faden et al., 1986, p. 2781.
A policy definition is: The competent subject's voluntary consent aRer disclosure that the intervention
involves research and about its nature, consequences, risks, benefits, and alternatives (Federal Common
Rule, §116~.
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The Ethics of Human Subjects Research
53
participants, language barriers that led to confusion over whether subjects were participating in
research or medical treatment, and cultural differences that meant the Alaska Native subjects
were hesitant to refuse participation.
at the end of this chapter.
These issues are further elaborated in the justice section
2. "iT7he person involved should have sufficient knowledge and comprehension of the
elements of the subject matter involved as to enable him to make an understanding and
enlightened decision. This . . . requires that before the acceptance of an affirmative decision
by the experimental subject there should be made known to him the nature, duration, and
purpose of the experiment; the method and means by which it is to be conducted; all
inconveniences and hazards reasonably to be expected; and the elects upon his health or person
which may possibly come from his participation in the experiment. "
Dr. Robert Elsner (one of the three former AAL researchers who attended the public
hearing and the former director of the AAL analytical laboratory) and Dr. Rodah} told the
Committee that, to their recollection, fairly complete information was conveyed to both Alaskan
Native and military subjects. Dr. Rodah! said he informed the village elders about the purpose
of the study and what they wanted the volunteers to do, and that the elders were present as
interpreters while the procedures were being done e Dr. Elsner, who worked primarily with
military subjects, stated his belief that as much infonnation as possible should be provided to
all subjects. However, the interpreters' command of English was variable and in most cases
insufficient to adequately explain the research. In addition, the interpreters may not have
understood that they were recruiting subjects for research, rather than selecting villagers for
medical treatment. Finally, neither military subjects nor Alaska Native subjects were informed
that the }~3} capsules they swallowed were radioactive; this stewed from the researchers'
conviction that }~31 was harmless and therefore not an important element of disclosure. The lack
of terms for "radiation" was an additional barrier to information conveyance In Native
languages. The Committee believes that it might reasonably be asserted that experimental
administration of a substance known to be dangerous at higher doses should have been
accompanied, even in the 1950s, with disclosure about the possibility of unknown future risks.
Such caution would be required today for research.
Based on the hearing testunony and field interviews at Native villages, the Committee
firmly believes that most of the Native participants were not sufficiently briefed on the nature
of the research and that some may not have understood that the study was research rather than
treatment intended for their benefit (see Appendix B). The AAL research took place within a
general context that included multiple visits by a variety of authority figures to Alaska Natives,
for study, treatment, and other reasons. In addition, the basic framework of the AAL field
investigations into acclimatization tended to blur distinctions between therapeutic and
nontherapeutic medical actions, between anthropological and medical research, between
essentially risk-free and potentially risk-bearing research, between research and the provision
of basic medical care, and between researcher and physician. For example, the AAL physicians
with whom the Committee spoke during its meeting in Alaska stated that they ministered to sick
and injured villagers as soon as they came to a village because there was so little available care.
After giving such care, they then went on to conduct their research studies.
This combination of research, treatment, and other interventions created confusion about
whether a particular intervention was research or treatment, and bolstered the authority of
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54
The ALL Thyroid Function Study
researchers to obtain participation. If subjects of research are permitted to infer that they are
receiving treatment intended for their benefit rather than participating in nontherapeutic research,
there is a fundamental flaw in the foundation upon which their understanding and consent are
based.
In the Committee's view, the researchers' task, even during the 19SOs, was to enable
subjects to understand; researchers may not merely assume their subjects' understanding. The
AAL researchers should have recognized the possibility of gaps\in subjects' understanding and
should have determined whether it was possible to eliminate or reduce those gaps. If the Alaska
Native subjects could not "make an understanding and enlightened decision" under the
circumstances, the research should not have taken place. It must be emphasized that
researchers, are not indeed cannot be- morally required to ensure their subjects' understanding
(see Faden et al., 1986; Beauchamp and Childress, 19941.
The Committee's criticism of the
AAL researchers is based on their lack of efforts to attend to, or reduce, linguistic and cultural
barriers- not on their failure to succeed.
In the Committee's opinion, what the researchers obtained was closer to mere cooperation
than informed consent. Given the cultural attitudes of the time, the AAL researchers may
genuinely, though mistakenly, have believed that the subjects' acquiescence was sufficient under
the circumstances. Perceptions about justice, cultural bias, and social sensitivity have developed
considerably since the 19SOs, and are discussed later in this chapter.
Most subjects who spoke with the Committee and to the team that went to the Native
villages asserted that they believed they were receiving treatment, and if they had understood
that the procedures they underwent were not for their benefit, they would not have participated.
The Committee is unable to determine the extent to which the subjects' recollections, as
expressed in their testimony, is colored by increased understanding or fear of radiation.
However, the Alaska Native belief system lends credence to their assertion. Belief systems at
the time were a mixture of traditional, supernatural, and Christian spiritual controls. Man was
seen as an integral part of his earthly surroundings. Although a doctor or dentist could treat the
physical ailments of a human, a shaman provided the way to communicate with spirit beings for
treating the forces of nature and ensuring protection from harm and disease (Marsh, 1954~.
These belief systems affected how the Alaska Natives perceived the causes of illness. The
traditional concept of illness was based on soul-Ioss, intrusion of a foreign object by sorcery
(Chance, 1961), or breaking a taboo (Burch in Smithsonian Institution, 1984, p. 344~. Thus,
for Alaska Natives the lack of direct benefit to subjects from the research and the possibility of
unknown risks would be associated with the likely occurrence of future harms to subjects or their
families. These harms would appear to the researchers as utterly unrelated to the research, but
to Alaska Natives could stem naturally from participation.
Although the Committee believes that the researchers did offer individuals an opportunity
to decline to participate, the offer came after the subjects had been recruited and were about to
be tested, making refusal awkward. The Nuremberg Code requires disclosure "before the
-
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55
acceptance of an affirmative decision" by the subject. Moreover, to decline to participate in
research is very- different from declining what is believed to be beneficial treatment. A subject
who misunderstood the nature of the intervention, believing it to be medical treatment, would
be unlikely to decline to participate.
Most of the surviving subjects who were interviewed remembered many details of the
procedures they experienced, but little or nothing that was recognizable as disclosure and
solicitation of consent. They remembered being told to "take tests" (an ambiguous term in
itself).~3 Two subjects did remember, along with the details of the procedures, being offered
the opportunity to withdraw. Because only one military participant was located and interviewed,
the Committee was not able to determine understanding on the part of the military subjects.
However, given the lack of language barrier, it seems likely that the military subjects' consent
to the research was voluntary and with understanding, except for the lack of disclosure of the
radioactive nature of the tracer.
3. "The duty and responsibility for ascertaining the quality of the consent rests upon
each individual who initiates, directs or engages in the experiment. It is a personal duty and
responsibility which may not be delegated to another with impunity. "
Because of the language barrier and the social and cultural organization of Alaska Native
villages, it was necessary and appropriate for the researchers to make use of village authority
figures as interpreters and to assist in the recruitment of subjects. However, some aspects of
the process of subject recruitment and information-giving were troubling to the Committee. The
difficulties of adequate translation in this setting have already been described; in addition,
however, the village elders were essentially given unsupervised authority for subject recruitment,
under circumstances where no researchers were available to monitor the process, to supplement
and correct the information given, or to answer questions before villagers Imade the commitment
to participate. Thus, through the recruitment process the researchers delegated to others to
others their nondelegable duty to obtain the subjects' informed consent, and compromised the
subjects's understanding and voluntariness. It also appears that the interpreters conveyed initial
information to prospective subjects without having the researchers present to make corrections
or answer questions. Since the researchers did communicate with enrolled subjects Trough
Abased on testimony at the hearings and in villages, subjects viewed themselves as obligated
participants from the moment they volunteered or were identified by the elder or interpreter, before they
had any opportunity to hear details of the research from the researchers.
~ The Committee heard historical testimony (from Robert Fortuine, physician and historian) that
health services were provided to Alaska Natives by the U.S. Department of Education before the Bureau
of Indian Affairs took on that function. Thus, it seems logical to speculate that Alaskan Natives who
recalled "taking tests" and "the studies" were not merely using simple terms for research or experiment,
but were also reflecting their confusion at the time over the blurring together of education, health care,
and non-therapeutic research. The researchers' emphasis on teaching and learning, while intended to
convey respect for Native survival skills, probably added to the confusion. Dr. Rodah] himself stated
very emphatically, "We were scientists; we were researchers." His clarity of purpose did not seem to
be transmitted to the Alaska Native subjects.
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The CAL Thyroid Function Study
interpreters during the conduct of the research to explain what the subjects were expected to do.
their failure to take part in the recruitment process is noteworthy. Moreover, although the
physicians needed interpreters to communicate and the use of village authority figures accorded
respect to village leadership and customs, the approach could convey the impression that
participation was expected for the good of the village. Thus, while the Committee believes the
elders had to be involved, that involvement should have been carefully orchestrated, with the
hill involvement of the researchers, to overcome language problems (both of translation and of
conveying concepts like research verson treatment, and radiation) and to help balance the
authority of the elders with information and assurances that nonparticipation was acceptable.
What happened instead is that the researchers apparently relied on the elders to bring back
volunteers, who were assumed to be willing and were then told what to do, carefully and in
some detial. The same amount of detail and oversight should have accompanied the recruitment
process.
The notion of seeking informed consent from individuals was certainly not foreign to
Alaska Natives at the time. Although Native peoples, including Alaska Natives, emphasize
cooperation and community, individuals still have important rights and interests (see, for
instance, Tjsselmuiden and Faden, 1992~. Moreover, Alaska Natives were not outside American
legal structure: even though Alaska did not become a state until 1959, Alaska Natives in the
Territory of Alaska were United States citizens at the time of the research, according to the
Compiled Laws of Alaska §20-~-7 (1952~. Thus, they enjoyed all the rights and interests of
American citizens. The Committee agrees that it was appropriate for the researchers to ask
village elders to begin the process of subject recruitment, but after this political] courtesy the
researchers themselves should have obtained the voluntary and informed consent of individual
subjects, using village elders to assist in translation of necessary information during the consent
process.
~.
J
The Common Rule and the AAL Research:
Looking Back from the 199Os
Although the basic requirements of the Nuremberg Code as applied to the AAL research
are still applicable today, under the terms of the Common Rule current concerns give even more
emphasis to protecting vulnerable minorities or regions wielding relatively little political
influence. Much of this increased attention to and understanding of justice issues is relatively
new; many of the questions now framed in justice terms have not yet been well answered (see
Beauchamp and Childress, 1994; National Commission for the Protection of Human Subjects of
Biomedical and Behaviourial Research, 1979~.
Justice in research design, according to the Belmont Report and the regulations that were
the precursors to the federal Common Rule, is addressed primarily by the equitable selection of
research subjects. Research subjects must be treated individually as capable adult decision-
makers, deserving of respect, equal treatment, and fair dealing. Where populations of subjects
are vulnerable to exploitation because of cultural differences or economic or social inequalities,
special care must be taken to guard against their exploitation as subjects of research. Sometimes
minorities are continually sought as research subjects for reasons of administrative convenience,
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57
such as when they are readily available in settings where research is ongoing. Social justice
requires that researchers consider the appropriateness of adding to the cumulative research
burden on any particular person and groups. The federal Common Rule, which applies to
Department of Defense research, similarly requires that the selection of subjects be equitable,
taking into account the purposes of the research, the seeing in which it is conducted, and the
special problems of involving vulnerable populations such as economically or educationally
disadvantaged persons (Common Rule §111(a)(3)).
The perspective of justice becomes clearest in examining the context in which the AAL
research took place as a whole, rather than the thyroid experiment in isolation. Although the
principle of justice had been invoked in connection with human subjects research prior to the
1950s, at the time of the AAL research the perception of injustice resulting from social biases
against minority populations was not well developed. In retrospect, a variety of activities over
many decades seem to have made use of the lands and peoples of Alaska as means to the ends
of others, with insufficient consideration of Alaska Natives as autonomous persons with interests
of their own. Alaska Natives today believe that they and their lands have been unduly burdened,
not only by research, but by a variety of other historical impositions.
The cultural characteristics of the Alaska Natives and the researchers, combined with the
social and historical context at the time of the AAL research, made it highly likely that Alaska
Natives would submit to the authority of researchers, and that the researchers would take
acquiescence as consent. The general context of multiple interventions experienced by Alaska
Natives for a variety of reasons by a variety of authorities ensured confusion between research
and treatment, and bolstered the authority of researchers to dispense benefits as they chose.
Indeed, during testimony to the Committee some Alaska Natives who had been subjects of
medical research had difficulty recalling which of the studies they had participated in was under
. .
c .lscusslon.
At the time of the AAL research, villages both welcomed strangers and had grown
accustomed to impositions by outside figures in authority. Alaska Natives considered
disagreement impolite, and religious, federal, and military visitors expected acquiescence from
them. The Committee found that' with the exception of Fort Yukon (which had a private
hospital), visits by physicians of any kind to the rural Native villages of this study were rare in
the mid-19SOs, and that physicians were welcomed with open arms.
Language was clearly a barrier to comprehension in the AAL study. One of the study
participants from Arctic Village told the Committee that she and the members of her family,
including the tribal leader, spoke no English at the time, so they just nodded at everything the
doctor said. Some village council members and tribal elders had begun to speak English as a
second language at the time, but effective communication was still difficult. VanStone (1956)
wrote on the subject of contacts between the U.S. Air Force and Alaska Natives:
Problems of understanding naturally arise between peoples who have been brought up in different
language systems, even though one party may have a working knowledge of the other's language.
Military personnel will find speakers of English in every Eskimo village in Alaska. In most of
the villages of northwest Alaska, a large percentage of the population speaks and understands
some English. Only the older people have no working knowledge of the language. l:t should be
kept in mind, however, that even when a seemingly successful conversation is being carried on
in English, there are many opportunities for mix-understandings to arise. When a person is
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The CAL Thyroid Function Study
having difficulty in making himself understood in a language that is not his own, the natural
tendency is to agree to whatever assistance the other party to the conversation is giving. It is a
very easy matter to put words into another person's mouth as a part of the painful process of
trying to help him express himself. Thus, military men attempting to get directions and other
types of information from Eskimos should speak slowly and distinctly. The urge to push a
conversation along desired lines, though sometimes irresistible, is very apt to lead to
misunderstandings, since the Eskimo will not have time to order his thoughts in the foreign
language and express himself clearly.
The problem of language barriers was also reported more recently by Morrow (1992),
who found that in courtroom and legal situations Alaska Native Yup'ik defendants almost
always answered the court's scripted questions with predictable "correct" responses, even when
it was made apparent that the person did not understand several of the points to which he had
agreed. According to Chance (1961), the traditionally passive role of Native women is reflected
in responses to medical questioning where they defer to men. He also noted that owing to a
cultural emphasis on self-reliance, anxiety is not permitted to be expressed overtly. In the
Committee's view, Dr. RodahT and other AAL researchers genuinely seem to have believed that
the villagers' welcoming attitude indicated eager cooperation, and that their relationship with the
subjects was one of trust and respect. Although this belief may have been paternalistic, it was
commonly held (not only in the Territory of Alaska, but among many cross-cultural researchers
at the timed, and more culturally astute anthropological guidance was not available to the U.S.
Air Force until at least 1 956 (VanStone, 1956), as the AAL research was coming to a close.
The complex contextual problems raised by cross-cultural research and research with
subjects suffering significant relative economic deprivation continue to this day to give rise to
violations of autonomy and justice. Some in the scientific community continue to believe that
research without significant risks is justifiable, despite barriers of language and culture.
However, both the Nuremberg Code and current standards dictate that if the disclosure process
cannot enable subjects to make decisions based on adequate understanding, then the research
should be forgone.
Another issue related to justice is whether the research itself is designed to benefit the
subject population. In weighing the risks and benefits of this study, it is necessary to look at
one a~sproport~onate~y nigh numbers or Alaska Natives selected to participate. The AAL
research was performed to help prepare Air Force personnel to fight and survive in a possible
future war fought in the Arctic. The purpose of the research was to gather information about
physiological mechanisms of cold adaptation; the expected benefits were to be directly relevant
to the protection of military personnel and indirectly relevant to the protection of all American
citizens. Although the disproportionate burden upon Alaska Native subjects might be justified
in terms of the greater good of national security, this justification would be sufficient only if it
were necessary to use Alaska Native subjects almost exclusively.
Indeed, because the research involved the adaptation to exposure to cold, the researchers
argued that the Alaska Native population was uniquely suited for study. However, with hindsight
there is a flaw in that logic. The purpose of the research was to determine (~) whether thyroid
function changed as a result of exposure to cold and (2) whether differences in thyroid function
in extreme cold resulted from long-term acclunat~zation to cold or from inherent racial and
ethnic differences. If long-term acclimatization to cold was to be effectively distinguished from
=4 _ ~ ~. 1 _ 1_ · _ 1 1 r A 1 _ 1 _ ~ ~, · ~, ~
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59
racial differences in thyroid function, the }~3{ Slay ought also to have included long-term
residents of Alaska who were racially and ethnically different from Alaska Natives (the military
subjects) were relative newcomers to the environment). When the Committee asked why white
Alaskans who were long-term residents had not been included, Dr. Rodah! said that recruitment
of such subjects, although desirable, was not possible. This reinforces the impression that the
Alaska Natives represented a subject population of convenience. The Committee recognizes that
Alaska Natives were needed as subjects to answer the research question; however, their
disproportionate numbers by comparison with military personnel, and the researchers' failure
to seek out indigenous non-Native subjects, emphasizes that their relative lack of understanding
may have made Alaska Natives easier to recruit.
_ _ _ _ in,
The Committee recognizes the difficulties of research design and subject selection under
the circumstances in which the AAL researchers worked. The researchers seem to have
considered their repeated use of a population of convenience as an exchange of benefits between
two groups. However, the Alaska Natives do not now- and state that they did not then share
this understanding.
According to the Belmont Report and the Common Rule, today the placement of this
undue burden of research participation on the Alaska Native population would require special
protection for these subjects. For example, if this research were to be approved today, the
researchers might be required to take special care to minimize the risks of the research and to
ensure the integrity of the process of informed consent. Specifically, it would become even
more important for researchers to communicate, and for subjects to understand, that they were
involved in research, not treatment, and that the purpose of the research according to the
research protocol was primarily to benefit military personnel. The Committee does not mean to
imply that Alaska Natives should never be involved in research, or to assume that they are
incapable of informed decision-making. It would certainly be wrong to deny any population the
opportunity to contribute to the development of knowledge. However, when."vuInerable
populations" with language and cultural barriers, like Alaska Natives, are subjects of research
today, researchers face an extra burden of responsibility to balance the potential benefit from
the research with the interests of, and risks to, the vulnerable population.
Finally, the Committee also considered whether the AAL researchers identified and took
action to help ameliorate the endemic goiter problem in Arctic Village and Anakruvuk Pass. The
Committee could not find evidence showing that the AAL provided medical follow-up after the
research, or that any explanation of the potassium iodide control experiment results was provided
to the research subjects. Dr. Rodah} told the Committee that he and his collaborating physicians
communicated regularly with physicians of the Alaska Native Service (ANS). He maintained
that a benefit of his work was that it called attention to the problem, so that the salt supply in
the local stores was replaced with iodized salt. Because of the lack of availability of historical
records from the AAL and the Indian Health Service from that time period, the Committee was
not able to verify the actual connection between the AAL research findings and actions by the
ANS to take corrective steps in locations with endemic goiter. However, AAL information
about the reduced salt intake and use of uniodized salt in those interior villages was conveyed
at scientific meetings in Alaska during 1956 and in subsequent papers. No Native interviewed
could remember follow-up return visits by U.S. Air Force or ANS doctors in the following
years, although this does not prove that the salt supplies were not changed. The Committee was
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The CAL Thyroid Function Study
told that a few subjects of the tests in Anaktuvak Pass subsequently had thyroidectomies; this
indicated there was an awareness of the problem in the medical community and possible
communication between the AAL physicians and the ANS.
If research by physicians uncovers a treatable condition, the duty of beneficence suggests
that the physician researchers have some follow-up responsibility to those subjects. The
provision of iodized salt, to be made available in the areas of endemic goiter, or even the
attempt to educate the affected communities, would have provided a benefit that did not interfere
with the research. Failure to take positive action that prevents harm is a lesser wrong than
taking action that causes harm. Nonetheless, having intervened in the lives of their subjects in
the course of their research, and having identified and studied the goiter problem, the AAL
physician-researchers had some obligation to ameliorate the situation of their subjects.
CONCLUSION
During the period of the mid-1950s when the AAL thyroid experiments took place, the
10 points of the Nuremberg Code set standards for the conduct of human subjects research.
Although the Code was established in response to an egregious abuse of scientific research and
prohibits research that is unnecessarily or excessively risky or harmful, as well as research that
is not designed to produce socially useful results, this does not mean that "good" research was
not subject to the Code's standards. In recognition of the importance of the Code, the AMA
had adopted its principles as a standard in 1947, and issues of informed consent and the Code
were discussed at length by the American Association for the Advancement of Science in ~ 953
in the journal Science. By adopting the Code's main points in the Department of Defense,
classified memorandum of 1953, the Air Force Surgeon General became responsible for
ensuring that these consent requirements were met by the physicians trader his command,
including the AAL. In turn, the AAL physicians and the Air Force were responsible for
ensuring that they received the voluntary and informed consent of individual subjects.
The Committee determined that because information on the nature of the {~3] tracer was
not disclosed, the military and Native subjects were not completely informed about the nature
and risks of the experiments. This omission was a wrong to the subjects, even though the risk
of hann was believed at the time to be nonexistent and has since been determined to be quite
low. In most of the Native villages, the AAL physicians accepted as volunteers those Natives
who were brought to them by village elders or other Native intermediaries without inquiring
as to what the subjects had been told. The elders or other intermediaries used by the AAL
physicians did not have sufficient training in medicine or science to explain the research
adequately, and many of the Native witnesses for the Committee thought they were receiving
a beneficial medical treatment. Minor children were used as research subjects without adequate
parental consent. Few of the Alaska Native subjects understood that they were participating
in research. None of the subjects, neither Alaska Natives nor military personnel, were
informed that they were taking a radioactive tracer. Thus, the Committee believes that the
experiments were conducted without informed consent, even according to the standards of the
time.
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Under current standards (represented by the Common Rule adopted by the Department
of Defense), the--complete experiment, its purpose, and potential risks and benefits would have
to be explained to the subjects, and permission to proceed would be required (usually in
writing). Thus, the AAL experimental design and consent procedure would fall short by
modern informed consent standards.
The experiments raise justice concerns according to current ethical standards by virtue
of the way a minority population was used. The Committee's examination strongly suggests
that the Native population was used primarily because it was a convenient research pool, with
an assumed understanding that the research would be conducted in exchange for medical care-
giving but without full disclosure about the nature of the research. Although the Alaska
Natives brought special physiological characteristics because of their long-term adaptation to
the climate, Tong-term white Alaska residents were not sought.
The AAL researchers held a genuine belief, justifiable at the time, that the research they
were conducting was both harmless and necessary. However, the Committee's examination
shows that the process by which the researchers obtained consent was flawed because none of
the subjects were provided with a full understanding of the nature of the research. The Alaska
Native subjects also were wronged by the nature of the subject selection process and by the
exploitation (even if unintentional) of language and cultural differences, which substantially
reduced the likelihood that they would even understand that they were the subjects of research
rather than the beneficiaries of medical treatment.
Given that the researchers and their Air Force superiors made errors of omission that
were typical in the research of the times, it is important not to assign blame for these
deficiencies. instead, the appropriate response is to acknowledge their errors in the hope of
ensuring that similar ones do not occur again.
Representative terms from entire chapter:
alaska natives
