September 20, 1997
Losing oneself to science?
By EVELYN STRAUSS
Once a physician has removed cells from a
person's body, who owns them? Who decides who can use them and for what
purposes? Is the person's control over his or her tissue severed along with
the cells themselves?
In the late 1950s, pathologist Oscar Auerbach nailed down the link between
smoking and lung cancer by examining tissue taken from the airways of several
hundred people during autopsies. When he compared his observations with
information gathered during interviews with relatives of the deceased, he
discovered that lung cells reflect smoking habits: the more cigarettes, the
greater the damage (SN: 8/19/61, p. 120). Surgeon General Luther L. Terry
cited Auerbach's findings in his first report on the dangers of smoking, and
many people credit that research with motivating the warnings that cigarette
packages carry to this day.
Auerbach's studies would raise concerns in the 1990s, however. The people
whose tissue samples he examined never agreed to participate in the project.
Furthermore, researchers these days can look for inherited as well as acquired
bases of disease (SN: 11/5/94, p. 298; 12/17/94, p. 408).
Suppose a researcher found a correlation between the presence of a certain
gene and lung cancer. Should he or she tell family members who may be at risk?
Even if there's no way to prevent or cure the disease? And knowing that their
health insurance companies or employers might misuse such information (SN:
10/26/96, p. 262)? What about people who might not want to contribute their
tissue, even after death, to some kinds of research projects -- such as
searches for possible genetic roots of sexual orientation?
"Because of the power of genetics, you can study these materials and
find out secrets about a person and his or her relatives," says Arthur L.
Caplan, director of the Center for Bioethics at the University of Pennsylvania
in Philadelphia. "The old rules for taking tissues aren't cutting it
anymore." The issue comes down to how much control an individual should
retain over the use of material from his or her body and the information
derived from it. Researchers, ethicists, advocacy groups, legislators, and
others are wending their way through the labyrinth of dilemmas surrounding
appropriate research on tissue.
Although most participants in the debate seem to agree on the goals --
providing protection and respect for individuals while continuing to support
research -- recipes for success differ. Many ethicists and others proclaim
that tighter control is essential to ensure personal privacy and autonomy,
while many biomedical investigators envision their research mired in excessive
cost and administrative burdens.
"The legal and ethical issues about the use of stored tissue are
probably the most profound, complex, and troubling of any ethical issue we
have in science today," says Lawrence O. Gostin, a professor of law at
Georgetown University in Washington, D.C. "It pits two fundamental values
against each other, and there's no easy resolution."
Federally funded research on tissue that
can be linked to living persons is tightly regulated. The individuals must
give specific consent for the research, or the investigation must meet certain
criteria, such as imposing minimal risk upon the subjects. Decisions governing
whether projects fulfill these conditions fall to groups called Institutional
Review Boards (IRBs), which consist of scientists and other representatives of
the local community.
Despite the regulations, plenty of room for controversy remains. Various
IRBs interpret the guidelines differently, and people disagree about whether
these groups should wield more or less power than they do now. Furthermore,
because people who have died are not technically "human subjects,"
the rules don't apply to many stored samples, says J. Thomas Puglisi of the
Office for Protection from Research Risks in Rockville, Md. -- even though
investigations on such materials may reveal information that could affect
surviving relatives.
Policy makers have begun proposing, and in some cases passing, legislation
aimed at protecting individuals. Many researchers say that some of the
regulations would erect unnecessary barriers between themselves and the
tissues they rely on for medical research. "People are in so much of a
rush to legislate, they're writing things with language that's so sweeping, it
has all kinds of unintended consequences," says David Korn, senior vice
president for biomedical research at the Association of American Medical
Colleges in Washington, D.C.
Several states have enacted legislation that deals specifically with the
use of tissue in research. A 1995 Oregon law, amended last July, grants
ownership of tissue, as well as the information derived from it, to the person
from whom it was taken. In contrast, the California supreme court ruled that a
man whose cells were used to make a valuable commercial product could not
claim a share of the proceeds. The court did find that the doctors had
violated the man's rights by not informing him of what they were doing with
the tissue.
Senator Pete V. Domenici (RN.M.) has introduced a bill aimed at
tightening the rules about use of tissue in genetic research. Even trying to
define words such as "genetic" presents problems, says Korn.
"You can get genetic information by all different approaches -- family
history, a variety of lab tests, or directly looking at DNA."
The National Bioethics Advisory Commission (NBAC) will make recommendations
regarding the use of human tissue in research in January 1998, says NBAC
genetics subcommittee chairman Thomas H. Murray.
Human tissue enters the research domain by
two main routes. In one, investigators ask volunteers to provide samples for a
research project. In the other, pathologists collect and store material left
over from medical procedures.
"Since microscopes began being used to study tissue samples, these
tissues have provided the knowledge base on which our current understanding of
medicine rests," says Korn.
Current regulations aim to inform patients about what will happen to their
samples, at least if investigators use them in federally funded studies.
Anyone undergoing a medical procedure must indicate that they understand the
possible risks and benefits by signing a form. Many institutions incorporate
into their consent forms a request for permission to use surplus tissue for
research. These documents and the process of requesting such approval have
come under close scrutiny in the last several years.
"The forms stink," says Caplan. "People don't read them
because they're in language that's too difficult." The general language
about research may be too imprecise to provide meaningful -- and legally
binding -- permission, adds Gostin. People can't agree to a use if they don't
know exactly what they're agreeing to, he continues.
Most forms do not reveal how researchers intend to handle the information
they obtain in terms of confidentiality and privacy, says Robert F. Weir of
the University of Iowa College of Medicine in Iowa City. Weir published a
study on informed consent in the July-August and September-December 1995
issues of Irb. How much information should potential tissue donors receive?
Covering all of the possibilities may not be realistic. "At the time the
tissue is being removed, there's no way to tell the patient what kind of
technology may come up in the future," notes Korn.
Furthermore, many people -- not just investigators -- worry that too much
information might overwhelm potential research subjects, thereby interfering
with volunteer recruitment or education. "People get freaked out about a
five-page consent form," says Iowa's Richard G. Lynch, head of the
Federation of American Societies for Experimental Biology committee that's
addressing ethical issues in biomedical research. "They say, 'Leave me
alone. Just tell me where to sign.'"
At the same time, more informative consent forms may strengthen research
projects because "better-informed subjects will probably feel like
they're really partners," says Mary Ann Wilson, consumer staff
representative at the Alliance of Genetic Support Groups in Chevy Chase, Md.
"They're more likely to continue in the project."
The National Action Plan on Breast Cancer (NAPBC) in Washington, D.C., has
developed a prototype consent form in which participants make a few general
choices. They indicate whether scientists may use their tissue for research on
cancer. In a separate question, they can grant permission for use of the
tissue in studies of other health problems. The form also asks people to
specify whether they want to be invited to take part in future research.
"If it's a preventable disease, a lot of people want to know the results
of sample testing," says Abbey S. Meyers, president of the National
Organization for Rare Disorders in New Fairfield, Conn., "but most
conditions are not treatable -- like Alzheimer's, for example."
"When people give samples, they should be able to say, 'Use this to
save the world but leave me out of it,'" says Mary Jo Kahn of the
Virginia Breast Cancer Foundation in Richmond. She points out that even being
offered the choice of knowing can disturb people. "Someone can say, 'I
know something about you that you don't know; do you want to know it?' You're
either going to freak out and wonder forever or just ask.
"It's wonderful that we have the chance to develop good policy before
there is widespread [genetic] testing and before we make a lot of
mistakes," Kahn continues. "It just takes one 60 Minutes show to
make it so no one will sign a consent form." Even if people develop wise guidelines,
many dilemmas will remain. What should researchers do with the millions of
tissue specimens currently stored in pathology labs around the country? Most
of these samples are not accompanied by adequate consent forms because the
tissues were collected long before people became as sensitive to the issues as
they are today.
Researchers should either go back and get consent or start a new study,
says George J. Annas, a medical ethicist at Boston University School of Public
Health. Annas has drafted model federal legislation for the use of human
tissue in research. "It's not right for you to know more about people
than they do without their consent," he says.
The issue should be resolved on a case-by-case basis, argues Elizabeth J.
Thomson, program director of clinical genetics research at the National Human
Genome Research Institute in Bethesda, Md. "Researchers should ask, ŒDo
I need to use archival tissue when I know that consent was less than
adequate?'" she says.
"If the sample's been there for 50 years, it's absurd to request
permission," says Ellen W. Clayton, associate professor of law and
pediatrics at Vanderbilt University Medical Center in Nashville. "But if
it was last week and you know where the patient is, it would be pretty hard to
argue not to ask."
Many scientists contend that demanding consent for every purpose would
result in squandering a valuable resource. "Say I want to look at
outcomes of different treatment regimens on people who have a particular
mutation," says Mark E. Sobel, chief of the molecular pathology section
of the National Cancer Institute in Bethesda, Md. "If I can't use old
material and I want to look at outcomes, it'll be at least 5 years before I
start getting information and another 5 until it's really useful."
Korn suggests setting up a system whereby scientists can tap into follow-up
information. "I don't need to know who the patients are, but I need to
know what happened to them."
In principle, confidentiality can be achieved if someone strips the samples
of names and gives them numbers instead, retaining the key so researchers can
obtain information later in order to interpret their findings. IRBs review
proposals for such research and decide whether they meet the requirements for
waiving consent. Among other criteria, the board requires that it must not be
"practicable" to obtain informed consent. "That means almost
impossible," says Puglisi. "It's more than just inconvenient."
"Many of us would like to see a broader interpretation that would
permit the review board to waive informed consent for coded samples more
easily in some cases," says Sobel. Annas disagrees. "The IRB can
grant exceptions, and that's a problem," he says. "They're the weak
link in the current set of regulations."
Weak link or not, IRBs don't always get the chance to deliberate on
research use of stored tissue, says Clayton. "It's really easy to pull up
the medical records for everyone admitted to the hospital with condition
X," she says. "Then you can go look at those people's tissues. It
isn't allowed [without IRB approval], but it's as common as pig tracks."
Coded samples create a fundamental security problem: The person with the
key can put everything together. "A lot of these problems have been
solved in the banking industry," says Lynch. "I can go to the same
ATM as you and get into my account but not yours. I think we should be
preventing misuse, not preventing getting at information."
Federal regulations regarding informed consent do not apply to these
so-called anonymized samples as long as they were stored before a study began
and cannot be linked with the donor -- a condition not easily met, says
Puglisi. Such research comes at a cost, however: It can deprive participants
of medical information that might someday benefit them. Although participants in the debate over
who should control tissue have made great strides in understanding and
responding to each others' concerns over the last several years, many issues
remain unresolved.
"The problem at the beginning was that people were at different
tables, coming up with proposals to deal with the thing they were legitimately
concerned about," says Lynch. "Since they didn't know about the
other concerns, they created problems. Now we're all sitting at the same
table."
Murray suggests that solutions won't necessarily require a strict trade-off
between benefits for society and protection for individuals. "This isn't
a zero-sum game," he says. "There may well be some creative
responses that will maintain what we care about most with respect to both
research and privacy."
References:
Weir, R.F., and J.R. Horton. 1995. DNA banking and informed consent--Part
2. Irb 17(September-December):1. ______. 1995. DNA banking and informed consent--Part 1. Irb
17(July-August):1. References:
1961. Lung cancer study shows cigarettes major cause. Science News
80(Aug. 19):120. Fackelmann, K.A. 1994. DNA dilemmas.
Science News 146(Dec. 17):408. Fackelmann, K.A. 1994. Beyond the genome.
Science News 146(Nov. 5):298. Sources:
George J. Annas Arthur L. Caplan Ellen W. Clayton Lawrence O. Gostin Mary Jo Kahn David Korn Richard G. Lynch Abbey S. Meyers Thomas Puglisi Mark E. Sobel Elizabeth J. Thomson Robert F. Weir Mary Ann Wilson (Editor's note (Sept. 22, 1999): The contact information for the
Alliance of Genetic Support Groups is now 4301 Connecticut Avenue, NW,
Suite 404, Washington, DC 20008-2304, Web site: http://www.geneticalliance.org)
Boston University School of Public Health
80 East Concord Street
Boston, MA 02118
Center for Bioethics
University of Pennsylvania
3401 Market Street, Room 320
Philadelphia, PA 19104-3308
Division of General Pediatrics
Medical Center East 5028
Vanderbilt University Medical Center
Nashville, TN 37232-8555
Georgetown University Law Center
600 New Jersey Avenue, N.W.
Washington, DC 20001
Virginia Breast Cancer Foundation
P.O. Box 17884
Richmond, VA 23226
Association of American Medical Colleges
2450 N Street, N.W.
Washington, DC 20037
Department of Pathology
University of Iowa School of Medicine
Iowa City, IA 52242
National Organization for Rare Disorders
P.O. Box 8923
New Fairfield, CT 06812
Office for Protection from Research Risks
National Institutes of Health
MSC 7507
6100 Executive Building, Room 3B01
Rockville, MD 20892-7507
Molecular Pathology Section
National Cancer Institute
10 Center Drive
MSC 1500
Building 10, Room 2A33
Bethesda, MD 20892-1500
National Human Genome Research Institute
38 Library Drive, Room 617
Bethesda, MD 20892-6050
Program in Biomedical Ethics
110 MEB
University of Iowa College of Medicine
Iowa City, IA 52242
Alliance of Genetic Support Groups
35 Wisconsin Circle, Suite 440
Chevy Chase, MD 20815
References - all articlesSources
- all articles
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