Canadian Medical Association Journal 1996; 154: 241-244
The Dr. William Logie Medical Ethics Essay Contest is open to undergraduate medical students studying at Canadian universities. The contest, named in honour of Canada's first medical graduate, is sponsored by CMAJ. The following essay won the $1000 first prize in the 1995 competition.
Research in human molecular genetics has exploded in the past 20 years, transforming the basic life sciences into an immense industry with an increasing presence in medicine and society. Genetic etiologies have been discovered for many diseases such as inborn errors of metabolism, cystic fibrosis, hemoglobinopathies and several common malignancies. Genetic information can be used for diagnosis, prognosis and epidemiology. The dawn of gene therapy and molecular medicine promises improved treatment for many genetic and acquired diseases. When the Human Genome Project is complete, information on human genes will be available for a variety of applications and will raise many questions regarding its appropriate uses. Exploring the medical ethics of technologies such as molecular genetic testing is essential to ensure the responsible clinical application of new discoveries in human molecular genetics.(1)
Genetic testing for particular diseases offers a clear benefit to patients and society by reducing the impact of disease, improving the health of the population and lessening the burden on our health care system.
Molecular genetic analysis, however, appears inappropriate and unjustified in circumstances where genetic enhancement or discrimination may result. Which diseases warrant genetic testing and when is it appropriate to screen for disease-causing alleles? Should we restrict the use of genetic information for reproductive decision making? Can confidentiality of test results be assured?
Patient autonomy, social equality and respect for human life and dignity are ethical principles that should guide decisions about genetic testing.(2,3) In addition, the benefits to individuals and to the greater community must be weighed against the possible risks.
Top of document
Genetic testing for medical management
Diseases that are treatable and preventable should be candidates for genetic testing because a beneficial intervention is available for patients. Intensified surveillance for the first signs of disease or the administration of an effective treatment regimen could reduce the impact of disease.
As an example, screening women for mutations in the recently discovered BRCA1 and BRCA2 genes for inherited breast and ovarian cancer could identify those at significantly increased risk of developing these cancers.(4,5) More frequent mammograms or screening tests may allow early diagnosis, and diet modification or avoidance of known carcinogens may help prevent the onset of cancer. Continued research also may soon lead to improved cancer treatments or cures.
In an another example, people at increased risk for familial adenomatous polyposis coli (APC) and colon cancer could be screened for mutations in the APC gene and identified as candidates for prophylactic bowel resection.(6) Successful early treatment can improve a person's overall health and quality of life.
Genetic testing has associated risks.(7-10) Knowing one is "doomed" to develop a disease may cause anxiety. A person might refrain from having children because of the results, or the tests might provide a basis for discrimination by insurers or employers. In the course of genetic testing, accessory information may be obtained, such as evidence of nonpaternity -- an additional risk, if such information is disclosed to the patient. As well, false-negative or nondefinitive test results, such as a 20% risk of developing a disease, can leave patients unsure of their destiny.
After providing education and counselling about the risks and benefits of genetic testing, professionals must respect patient autonomy. Providing genetic information about preventable or treatable diseases is important when the information affects the patient directly. However, patients should be free to make their own reproductive or lifestyle decisions or even ignore medical advice based on the results of genetic tests.
Diseases that have no known treatment or method of prevention are less obvious candidates for genetic testing, although there may be some benefit for the patient. Genetic testing can sometimes confirm a diagnosis and dispel anxiety: the relief that one did not bring about an illness is justification for the testing. Schizophrenia and bipolar disorder are examples of diseases that could be legitimized through genetic testing -- although the benefit to the patient must be weighed against the guilt felt by parents who "gave" their child the disorder. This is particularly true for severe genetic disorders affecting children.
When no specific genetic mutation is associated with a disease, it may still be possible to identify an inherited component by testing family members for genetic markers that cosegregate with the clinical phenotype. However, genetic-linkage analysis necessarily involves other family members and thereby breaches the confidentiality of the patient. In order to obtain consent, details of the disorder as well as the risks and benefits of testing must be disclosed; relatives who prefer not to know their own risk for developing the disease or passing it to their children may be unwilling to cooperate. The autonomy of each family member who receives counselling and education must be respected. The benefits and risks must be outlined clearly and without coercion by the physician or by other family members.
If there is a preventable or treatable component to the disease, this type of genetic testing is a justifiable means of acquiring diagnostic information. If there is no intervention or course of action that would benefit the affected person, the risks of involving family members may be too great to justify genetic-linkage analysis.
Top of document
Predictive testing for reproductive decision making
Having children is a cherished privilege in today's society, and we are strongly motivated to ensure our children a healthy and happy life. Couples at increased risk for a genetic disease may wish to determine the likelihood that a child would inherit a genetic mutation. In-vitro fertilization allows an opportunity for genetic screening of embryos before implantation, and healthy embryos could be selected over those with disease-causing alleles.
Prenatal testing of the amniotic fluid or chorionic villi can provide similar genetic information, but at that stage termination of the pregnancy is the sole intervention to prevent the birth of an affected child. Prenatal diagnosis would be justified for diagnosing conditions that require strict surveillance or immediate care of the newborn, but may not be justified if the only alternative course of action is abortion. Diseases for which termination of the pregnancy is the only available intervention must be identified, but whether prenatal genetic testing should be permitted for these diseases will depend on society's view of abortion. Undoubtedly we all possess disease-causing genes, but which of these warrant screening to help in making reproductive decisions? How devastating would the disease have to be? How sure must we be that a cure for the disease is not imminent?
Genetic screening for the sole purpose of assisting in reproductive decisions may be justifiable if the defect would inevitably lead to a devastating illness for the child, since a child's pain and suffering could be spared. A further consideration may be that the resources needed to care for critically ill patients represent a significant burden on society. Principles must be adequately defined at the outset, or as the Human Genome Project progresses the list of candidate "diseases" will grow longer and the slope will become more slippery.
Genetic information sought to help people make decisions about reproduction should be restricted to diseases with such severe consequences that a child will lack autonomy, experience undue suffering and have an expected lifespan barely extending into the reproductive years. This would maintain respect for human life and dignity. Diseases that would allow an autonomous child to survive without undue pain and suffering should not be selected against by prospective parents: the slope is too slippery.
Eliminating mild disorders, physical disfigurement or behavioural attributes could make us intolerant of human variation; such decisions also represent a certain disregard for human life. We must avoid the use of genetic information to create ideal babies.
Fortunately, many attributes are controlled by numerous genes and involve complex interactions with the environment, making outcomes difficult if not impossible to interpret from genetic sequences. As a species, we depend on genetic variation for our successful evolution and we should not begin to influence or control the content of our own gene pool in such direct ways.
Top of document
Late-onset disorders as a special case
Late-onset diseases represent a curious dilemma for molecular genetic analysis.(11) People with late-onset disorders such as cancer, adult polycystic kidney disease and Huntington's disease can be asymptomatic for many years. With the pace of progress today, a child who is expected to develop Huntington's disease at age 50 may have the good fortune of being around when a cure is discovered. Should we allow consideration of these genes in the reproductive decision-making process?
The very definition of a late-onset disorder is unclear because some "adult" diseases such as retinitis pigmentosa, polycystic kidney disease and myotonic dystrophy can develop in childhood. "Late onset" usually refers to disorders that afflict a previously asymptomatic person some time during adulthood. Genetic testing for these disorders for the sole purpose of reproductive decision making should not be allowed; the prospect of many healthy years and the likelihood of a cure being discovered is enough to justify this position.
A clear distinction must be drawn, however, between using genetic information for reproductive decision making and using it for the direct benefit of the person being tested. Neonatal or population screening for late-onset disorders would be justified in certain cases if knowing the likelihood of developing a disease would significantly benefit the patient. Treatment or preventive measures could be instituted at the appropriate time, lifelong objectives or decisions could be made with this information in mind, and ruling out diseases such as polycystic kidney disease could avoid frequent examinations and screening tests -- a benefit to both the patient and society.
Screening the population for Huntington's disease has well-studied risks and benefits.(12) Although people at high risk often prefer to know if they bear the expanded DNA sequence predictive of the disease, patients who test normal may suffer because they "escaped" the disease. Studies regarding the impact of genetic testing for other late-onset disorders are forthcoming and will allow a better understanding of the risks and benefits of genetic analysis.
Top of document
Summary
The allocation of scarce resources to genetic testing will ultimately limit which diseases are subject to molecular analysis. Those that are associated with a beneficial medical intervention, be it treatment or prevention, should be given top priority.
Respect for patient autonomy and the confidentiality of test results must be strictly enforced to avoid abuse of genetic information. In a privately funded health care system -- the American system, for example -- genetic discrimination by insurers may limit the availability of medical care for affected people. However, recent documents tabled by the US Equal Employment Opportunities Commission declared genetic discrimination to be unfair, unjustified and illegal under the Americans with Disabilities Act.(13) Such legislation may help to reduce the threat of abuse in genetic testing.
Proper communication of genetic principles may pose the greatest challenge to genetic counselling and will require specially trained professionals.(14) Patients must be allowed to make informed and autonomous decisions regarding a genetic test, free from coercion by family members or the medical community. Education is critical in helping everyone involved understand the meaning of all possible outcomes and develop awareness of the various issues, risks and benefits.
Society must continue to discuss genetic disease and the responsible use of genetic information for making reproductive decisions. We can afford to be more liberal in testing patients because the risks and benefits are directly relevant, but with reproductive decisions the interests of future generations are at stake. There are other medical interventions that affect the collective gene pool, but few do so as directly or with so much intention. We must be careful in justifying access to our genetic information and making use of molecular genetic analysis, especially when we have only a partial understanding of the genes themselves.