Science, 1 November 2002
Human Subjects in Weapons Research
Arthur L. Caplan and Pamela Sankar
The threat that biological and chemical weapons might be used in the context
of armed conflict or by terrorists is frighteningly real. Advances in
genetics, microbiology, bacteriology, and cognate areas of biomedicine are
presenting a new array of threats to both military personnel and civilians.
Synthetic virulent strains of viruses and bacteria, "fusion" toxins, and
stealth viruses, along with novel modalities for delivering toxic agents
using organic and inorganic chemicals, foods, aerosols, and microdroplets,
have raised the concern of federal and state governments, national security
agencies, and the armed services. Research efforts, supported by significant
federal and private funding, are underway to find vaccines, drugs,
prophylactic agents, and palliating interventions that might mitigate these
The explosion of research in this area has created an important but
little-discussed ethical challenge. Many institutions are struggling with
issues raised by the design and oversight of research protocols that call
for the deliberate exposure of human subjects to toxic and noxious agents.
Some of this research will of necessity be done secretly, despite the fact
that, as at least one federal panel noted nearly a decade ago, this poses a
tension "between duties to disclose and the need to keep information
secret."* Federal regulators and scientific and medical journals will soon
be asked how to ensure that such experiments are carried out in a way that
is consistent with the highest standards of ethical conduct in the
protection of human subjects.
Contemporary human subjects protections apply almost exclusively to research
that seeks to produce generalizable knowledge that can be put to beneficial
use in biomedicine; for example, by creating new diagnostic tests, new
therapies, or new forms of prophylaxis against naturally occurring diseases.
Review bodies and regulators assess informed consent and risk/benefit ratios
in the context of research to improve health. There is little experience
with experiments that deliberately harm subjects.
Such experiments have, for the past two decades, been limited to three
areas. The first is research on treatments for common nonlethal viruses,
which requires first infecting subjects. The risks to subjects in these
types of studies are known to be very small. The second is "Phase One"
clinical trials, done to assess the safety of new drugs. The third is
challenge studies, in which basic physiological and psychological
information is sought about reactions to various stimuli. Current ethical
standards require that subjects in such studies be closely monitored and
that risks be kept to a minimum.
Research involving biological or chemical weapons must necessarily involve
exposures to toxic agents and levels of risk higher than those that exist in
most research. Such research would seem to compromise the core tenet of
medical ethics that studies should not knowingly do harm. Indeed, the
Environmental Protection Agency now refuses to accept toxicity tests done on
human subjects in order to establish "safe levels." Yet national security
now places a higher premium on studies that might pose similar risks, and
many prospective subjects might wish to volunteer from a sense of duty or
patriotism or for personal financial gain.
There is every reason to believe that such work will move forward rapidly.
If so, clear guidelines are needed for establishing its unequivocal
relevance to national security concerns. These guidelines must also address
who may be recruited as subjects, what level of competency they should
demonstrate, how the freedom of their choice can be ensured, what types of
end points will be used, what compensation they will be given, and what
level of oversight will be in place. Investigators, review committees, and
journal editors will need guidance about the kinds of harm that can be
associated with this research and the ways in which restrictions on the
dissemination of research results should shape their assessment of its
Some will surely argue that no form of research involving the deliberate
harm of human subjects ought be tolerated. Such a policy could be put in
place. It would have obvious implications for the speed with which antidotes
to biological and chemical weapons can be found and the confidence that
those receiving them can have in their efficacy. If, on the other hand, the
need to hasten discovery in this area leads us as a nation to permit such
research, it is imperative that the norms needed to ensure that it is
conducted fairly and humanely be formulated, then widely discussed and
thoroughly debated as soon as possible.
Arthur L. Caplan and Pamela Sankar are in the Department of Medical Ethics
at the University of Pennsylvania, Philadelphia, PA.
Stuart A. Newman, Ph.D.
Department of Cell Biology and Anatomy
Basic Science Building
New York Medical College
Valhalla, NY 10595
Tel: (914) 594-4048
Fax: (914) 594-4653
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