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Phase I Home Page
The Language of
Bioethics (Glossary)
Objectives
Goals
Required
Reading
Suggested
Reading
Clinical
Vignettes
Key Terms
Genetic
Screening
Genetic
Therapy: Complex Ethical Issues
Proposed
International Code of Ethics for Medical Genetics: Eight Ethical Issues
Genetic
Privacy & Nondiscrimination Act
Gene Therapy
Genetic
Disorders: A Special Use?
Topical
Questions
Suggested
Reading
References
& Resources
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Introduction to Medical Ethics and Genetic
Testing, Screening and Gene Therapy
Introduction to Medical Ethics
To provide a foundation for subsequent
discussions by introducing the appropriate glossary, technique and substantive
resources for clinical ethics discourse. To introduce a standard format and
method for discussion and provide an opportunity for practice.
Genetic Testing and
Technologies
Objectives
To explore the use of new diagnostic and
intervention technologies, i.e., decisions about screening, the disclosure of
test results to patients or others, the relative risks and benefits of gene
therapy, and issues of genetic privacy and nondiscrimination such as may occur
in the workplace or in insurability.
Goals
- Identify major ethical issues of genetic
testing, screening and gene therapy.
- Understand confidentiality and disclosure
issues related to genetic testing.
- Understand the obligations of the physician to
his patient regarding genetic testing.
- Understand that identification of a genetic
disorder is not always in an individual patient's best interest.
- Appreciate the need for skilled genetic
counseling.
Required Reading
Code of Medical Ethics, American
Medical Association, p 21-28.
Clinical
Vignettes
Vignette #1
A patient is tested for the gene for
Huntington's Disease and is positive. The test also revealed the fact that the
father was not the biologic father. Does the physician need to tell the
patient this information?
Vignette #2
The genetic cause of mental retardation of a
man in his mid-40's is determined. The man's sister is his guardian and has
two daughters. The physician wants to warn the two daughters they are at risk
for bearing a retarded child. The mother refuses to let the physician do so
because she does not want to be party to giving them information that might
lead to an abortion. What does the physician do?
Vignette #3
The mother in the family has had both uterine
and colon cancer at an early age and is found to have a MLHI gene mutation
which increases the risk of colon cancer to 85-90%. There are four adult
children. Should they be advised to have testing for this mutation and run the
risk of not being able to obtain health insurance?
Video–A Question of Genes: Inherited Risks
Key Terms
- Genetic testing: the use of specific assays to
determine the genetic status of individuals already suspected to be at high
risk for a particular inherited condition.
- Genetic screening: distinguished from genetic
testing by its target population. It is the systematic search of populations
for persons with latent, early or asymptomatic diseases.
- Gene therapy: the use of genetically altered
material to favorably treat illness in humans.
Clinical genetics encompasses
all ethical issues in medicine and health care. Major ethical issues deal with:
- Truth-telling
- Paternalism
- Confidentiality
- Rationing
- Role of the genetic counselor
- Neutrality vs. Expressing Opinion
- Is the physician expressing an opinion in
genetic issues different, for example, than expressing an opinion
regarding toxic chemotherapy for cancer?
- Should neutrality be maintained if a woman
knows her fetus is affected with Tay-Sachs disease or Lesch-Nyhan syndrome
and asks for advice?
- Should the counselor be open and direct
about his biases rather than conceal them behind a cloak of neutrality?
In summary, genetic counseling should serve the
patient's interest and values but be balanced with legitimate societal needs
and wants, including the general public health. (e.g., to screen all pregnant
women for carriage of cystic fibrosis gene might cost in excess of one billion
dollars annually.
Genetic Screening
- Identify patients who may benefit from
pre-symptomatic treatment
- Identify persons at risk for having an
affected child
- Research purposes
- Failure to recognize the heterogeneity of
the disorder (e.g., in the early days of phenylalanine screening, infants
were falsely labeled because of high phenylalanine levels as having the
disease).
- Failure to test efficacy of the intervention
with properly designed and peer-reviewed studies.
- Failure to inform prospective patients or
their parents that the program is experimental.
- Essential Components of the Ethically
Defensible Mass Screening Program
- Clear statement of purposes and goals
- Peer-reviewed pilot studies showing that
stated goals can be achieved with acceptable costs and adverse effects.
- Education of the target population
- Attention to traditional standards of
informed consent (avoiding mandatory programs except when compelling
argument exists for doing so)
- Respect for confidentiality of potentially
stigmatizing information
- Prenatal diagnosis and termination of
pregnancy option exists
- Can prenatal diagnosis be justified by those
who believe abortion is immoral?
Genetic Therapy:
Complex Ethical Issues
- Whether to restrict initial efforts to
patients with the capacity to consent.
- Whether to do first trials on patients with
end stage disease who have little to lose, or patients early in their course
who have the greatest potential for a successful outcome.
- Whether to try treatments that could prolong
the life of patients with severe neurologic impairment, possibly without
improving their condition.
- Somatic gene therapies pose new ethical issues
for the individual patient but germ-cell therapies, such as inserting genes
into fertilized eggs, affects not only the life of that individual but the
potential of all his or her offspring, thus introducing additional complex
ethical issues.
Proposed
International Code of Ethics for Medical Genetics: Based on Eight Ethical
Issues
- Equitable distribution of genetic services
(i.e., access to/demand for)
- Respect for and safeguarding of personal and
parental choices (i.e., reproductive choices, including the choice of
termination of the pregnancy). Reproductive decisions should be the province
of those who will be directly responsible for the social and biological
aspects of childbearing and child rearing. The woman should make the final
decision among reproductive options without coercion from her partner, her
doctor or the law. Choice should include the economic and social ability to
act upon a decision, including decisions to terminate a pregnancy or to
raise a child with a disability.
- Confidentiality when other family members are
at high risk. Family members have a moral obligation to share genetic
information with each other.
- Protection of privacy from institutional third
parties. Insurers, employers, schools, government agencies should have no
access to genetics information about an individual without the person's
fully informed consent and should not be permitted to require genetic tests
without informed consent.
- Full disclosure of clinically relevant
information to patients, a prerequisite for free choice.
- Prenatal diagnosis should be performed only
for reasons relevant to the health of the fetus or the mother (i.e., not for
sex selection, or to solely benefit a third party).
- A voluntary approach to genetic services,
including genetic counseling, testing, prenatal diagnosis, presymptomatic
testing, and screening in the workplace for susceptibility to occupationally
related diseases. The only exception to the rule of voluntary screening
should be newborns only if early treatment is available that would benefit
the newborn (i.e., then screening should be mandatory).
- Emphasis on non-directive counseling.
Genetic Privacy and Nondiscrimination Act of
1995, 1996, 1997, 1998 (GPNA)
*(None thus far enacted)*
- Legislative protection: grants a proprietary
interest in one's own genetic material, protects individual rights and
simultaneously promotes continued research and development by establishing
clear rules on which investors and the biotechnology industry may rely.
- Addresses disclosures and limitations
regarding genetic information; prohibits disclosure of an individual's
genetic information without written consent.
- Exception: permits disclosure if it pertains
to authorized paternity testing, medical testing of a descendant's
relatives, identification of bodies, court-ordered disclosure, and if it
furthers authorized moral investigation.
- Prohibits employers from obtaining genetic
information for purposes of discrimination or restricting rights or benefits
of current or prospective employees.
- Prohibits health insurance providers from
using genetic information to affect health insurance in any way and prevents
use of genetic information as inducement to purchase insurance.
Human Genome Project: In process of
mapping the entire human gene system.
Gene Therapy
Ashanti/NIH: First approved gene therapy
procedure on 4-year old with rare genetic disease, severe combined immune
deficiency (SCID). Her own white blood cells were genetically modified and
infused back into her blood stream.
Distinction between therapy on somatic
(non-reproductive) cells and germ (reproductive) cells. Only germ cells carry
the genes that will be passed on to the next generation.
- Arguments in favor of Gene Therapy:
- Potential for treating ill patients or
preventing onset of severe illness (when conventional therapy has failed).
- Somatic-cell gene therapy is like any other
new medical technology
- To prevent research on gene therapy is to
infringe upon intellectual freedom of researchers.
- With current rate of progress in gene
therapy techniques risks become more identifiable and outcomes can be
predicted rather precisely.
- Germ-line gene therapy: offers true cure;
may be only effective way of addressing some genetic diseases by
preventing transmission of diseased genes. The expense of somatic-cell
therapy for multiple generations is avoided; medicine should respond to
the reproductive health needs of prospective parents at risk for
transmitting serious genetic diseases; scientific community has a right to
free inquiry within the bounds of acceptable human research.
- Arguments against gene therapy:
- "Slippery slope:" can we
distinguish between "good" and "bad" uses of gene
modification techniques?
- Potential for harmful abuse of the
technology
- Difficulty in following patients in
long-term clinical research, including surveillance of future generations.
- Many gene therapy candidates are children
who are too young to understand ramifications of gene therapy
- Potential conflicts of interest versus
interests of insurance companies or society in not bearing the financial
burdens of caring for children with serious genetic defects.
- Issues of justice and allocation: can we
afford the expense?
- Who should receive gene therapy? If only
those who can afford it, where is the principle of justice? Could we skew
the distribution of desirable biological traits?
- Long-term effects of germ-line therapy not
known.
- Opens the door to attempts at altering human
traits not associated with disease (i.e., eugenics).
- Violates rights of future generations to
inherit a genetic endowment which has not been intentionally modified.
- Too expensive.
- Essentially mates generations of
unconsenting research subjects (i.e., germ-line therapy involves research
on early embryos and affects their offspring).
- AMA Position Paper on Gene Therapy
- Research must conform to AMA
- Council on Ethical and Judicial Affairs
guidelines on clinical investigations.
- Gene Therapy must adhere to stringent safety
considerations.
- Gene therapy should be utilized for
therapeutic purposes in the treatment of human disorders and not for
eugenic purposes.
Genetic
Disorders: A Special Use?
- With regard to single gene disorders, there is
nothing the individual could do to avoid inheriting the gene: one's genotype
is immutable and gene expression is unavoidable in spite of improving
treatment prospects for some disorders; with few exceptions (e.g.,
phenylketonuria and dietary changes), no environmental, lifestyle or dietary
change can help the individual avoid the effects of a purely genetic
disorder; society would consider individuals with genetic diseases more
deserving of societal support than medical conditions attributable to
behaviors (e.g., cigarette smoking, alcohol and substance abuse)
- There is a family stigma associated with
genetic disorders
- Genetic traits sometimes fall along the line
of race and ethnicity: mandatory genetic testing and disqualification from
life insurance on basis of sickle cell disease, thalassemia, etc. that
primarily affect certain racial and ethnic groups raise troubling policy
issues.
- Given the history of eugenics (e.g. Nazi
Germany) there is reluctance to embrace any program of systematic
application of genetic criteria.
Topical Questions
- Should the six million women who become
pregnant each year be routinely tested for cystic fibrosis carrier state? If
so, who will pay for this?
- Should all women be tested for the genetic
mutations linked to breast cancer?
- Are there differences of ethical issues in
somatic-cell gene therapy and germ-cell gene therapy?
- Should only those who can afford it receive
gene therapy?
Suggested Reading
Note: These articles can be found through Ovid and will require an
ID and password.
- Fost,
N. Ethical Issues in Genetics. Pediatric Clinics of North America,
39 (1): 79-89. February 1992.
- Wilfond,
BS, Rothenberg, KH, Thomson, EJ, Lerman, C. for the Cancer Genetic
Studies Consortium, National Institutes of Health. Cancer Genetic
Susceptibility Testing: Ethical and Policy Implications for Future Research
and Clinical Practice. Journal of Law, Medicine and Ethics, 25
(1997): 243-51.
- Annas,
G J. Genetic Prophecy and Genetic Privacy-Can we prevent the dream from
becoming a nightmare? American Journal of Law and Medicine, 22(1):
109-34, 1996.
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