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An Introduction to Biomedical Ethics
Sunday, August 3, 2008
Ethical theories represent the grand ideas on which guiding principles are based. They attempt to be coherent and systematic, striving to answer the fundamental practical ethical questions:
What ought I do?
How ought I live?
Generally ethical principles stem from ethical theories, and when defending a particular action, ethicists normally appeal to these principles, not the underlying theory. Ethical traditions stretch back to earliest recorded history. Separate bodies of ethics, often not encompassing a true theory but rather a general system, were developed in India and China, and within the Jewish, Christian, Islamic, and Buddhist and Hindu religions. All of these theories represent altruistic, rather than egoistic, attitudes towards mankind. Some of the most commonly cited ethical theories include the following:
Natural Law
The system of natural law, often attributed to Aristotle, posits that man should live life according to an inherent human nature. It can be contrasted with man-made, or judicial, law, but they are similar in that both may change over time, despite the frequent claim that natural law is immutable, often tying it to particular religious beliefs.
Deontology
Deontology holds that the most important aspects of our lives are governed by certain unbreakable moral rules. Deontologists hold that these rules may not be broken, even if breaking them may improve an outcome. In other words, they may do the "right" thing, even though the consequences of that action may not be "good." The famous philosopher, Immanuel Kant is often identified with this theory. One example of a list of "unbreakable" rules is the Ten Commandments.
Utilitarianism
One of the more functional and commonly used theories, utilitarianism, sometimes called consequentialism or teleology, basically promotes good or valued ends, rather than using the right means. This theory instructs adherents to work for those outcomes that will give the most advantage to the majority of those affected in the most impartial way possible. (Simplistically, this theory advocates achieving the greatest good for the greatest number of people.) It is often advocated as the basis for broad social policies.
Virtue Theory
The virtue theory asks what a "good person" would do in specific real-life situations. This recently revived theory stems from the character traits discussed by Aristotle, Plato, and Thomas Aquinas. They discuss such timeless and cross-cultural virtues as courage, temperance, wisdom, justice, faith, and charity.
Values And Principles
Where Learned?
Values are the standards by which we judge human behavior. They are, in other words, moral rules, promoting those things thought of as good and minimizing or avoiding those things thought of as bad. We usually learn these values at an early age, from observing behavior and through secular (including professional) and religious education. Societal institutions incorporate and promulgate values often attempting to make old values rigid, even in a changing society. In a pluralistic society, clinicians often treat subjects having multiple and differing value systems, and they must be sensitive to others’ beliefs and traditions.
Ethical values stem from ethical principles. Ethical principles are action guides derived from ethical theories. Each of these principles consists of various moral rules, which are our learned values. For example, the values of dealing honestly with patients; fully informing patients before procedures, therapy, or being involved in research; and respecting the patient’s personal values are all subsumed under the principle of autonomy or respect for persons.
Although each person is entitled (and perhaps even required) to have a personal system of values, there are certain values that have become generally accepted by the medical community, courts, legislatures, and society at large. A respect for patients (often described as patient autonomy) has been considered so fundamental that it is often given overriding importance. Although some groups disagree about each of the generally accepted values, this dissension has not affected their application to medical care.
Assessing Patient Values
A key to making ethical decisions at the bedside is to know what the patient’s values are. In patients too young or incompetent to express their values, it may be necessary for physicians to make general assumptions about what the normal person would want in a specific situation or to rely on surrogate decision making. With patients who are able to communicate, however, care must be taken to discover what their own uncoerced values really are.
A typical ethically dangerous scenario is with a patient who refuses lifesaving medical intervention "on religious grounds." Typically, the spouse is at the bedside, does most of the talking, and may be influencing the patient’s decision. In those cases, it is incumbent on the clinician to question the patient alone to assess his or her real values.
What is gene testing? How does it work?
Gene tests (also called DNA-based tests), the newest and most sophisticated of the techniques used to test for genetic disorders, involve direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic examination of stained or fluorescent chromosomes. Genetic tests are used for several reasons, including:
- carrier screening, which involves identifying unaffected individuals who carry one copy of a gene for a disease that requires two copies for the disease to be expressed
- preimplantation genetic diagnosis (see the side bar, Screening Embryos for Disease)
- prenatal diagnostic testing
- newborn screening
- presymptomatic testing for predicting adult-onset disorders such as Huntington's disease
- presymptomatic testing for estimating the risk of developing adult-onset cancers and Alzheimer's disease
- confirmational diagnosis of a symptomatic individual
- forensic/identity testing
In gene tests, scientists scan a patient's DNA sample for mutated sequences. A DNA sample can be obtained from any tissue, including blood. For some types of gene tests, researchers design short pieces of DNA called probes, whose sequences are complementary to the mutated sequences. These probes will seek their complement among the three billion base pairs of an individual's genome. If the mutated sequence is present in the patient's genome, the probe will bind to it and flag the mutation. Another type of DNA testing involves comparing the sequence of DNA bases in a patient's gene to a normal version of the gene. Cost of testing can range from hundreds to thousands of dollars, depending on the sizes of the genes and the numbers of mutations tested.
What are some of the pros and cons of gene testing?
Gene testing already has dramatically improved lives. Some tests are used to clarify a diagnosis and direct a physician toward appropriate treatments, while others allow families to avoid having children with devastating diseases or identify people at high risk for conditions that may be preventable. Aggressive monitoring for and removal of colon growths in those inheriting a gene for familial adenomatous polyposis, for example, has saved many lives. On the horizon is a gene test that will provide doctors with a simple diagnostic test for a common iron-storage disease, transforming it from a usually fatal condition to a treatable one.
Commercialized gene tests for adult-onset disorders such as Alzheimer's disease and some cancers are the subject of most of the debate over gene testing. These tests are targeted to healthy (presymptomatic) people who are identified as being at high risk because of a strong family medical history for the disorder. The tests give only a probability for developing the disorder. One of the most serious limitations of these susceptibility tests is the difficulty in interpreting a positive result because some people who carry a disease-associated mutation never develop the disease. Scientists believe that these mutations may work together with other, unknown mutations or with environmental factors to cause disease.
A limitation of all medical testing is the possibility for laboratory errors. These might be due to sample misidentification, contamination of the chemicals used for testing, or other factors.
Many in the medical establishment feel that uncertainties surrounding test interpretation, the current lack of available medical options for these diseases, the tests' potential for provoking anxiety, and risks for discrimination and social stigmatization could outweigh the benefits of testing.
For what diseases are gene tests available?
Currently, more than 1000 genetic tests are available from testing laboratories. Some gene tests available in the past few years from clinical genetics laboratories appear below. Test names and a description of the diseases or symptoms are in parentheses. Susceptibility tests, noted by an asterisk, provide only an estimated risk for developing the disorder. Contact GeneTests for comprehensive information on test availability and genetic testing facilities.
Some Currently Available DNA-Based Gene Tests
- Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease)
- Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death)
- Alzheimer's disease* (APOE; late-onset variety of senile dementia)
- Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers)
- Gaucher disease (GD; enlarged liver and spleen, bone degeneration)
- Inherited breast and ovarian cancer* (BRCA 1 and 2; early-onset tumors of breasts and ovaries)
- Hereditary nonpolyposis colon cancer* (CA; early-onset tumors of colon and sometimes other organs)
- Central Core Disease (CCD; mild to severe muscle weakness)
- Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs)
- Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism)
- Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections)
- Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness)
- Dystonia (DYT; muscle rigidity, repetitive twisting movements)
- Emanuel Syndrome (severe mental retardation, abnormal development of the head, heart and kidney problems)
- Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities)
- Factor V-Leiden (FVL; blood-clotting disorder)
- Fragile X syndrome (FRAX; leading cause of inherited mental retardation)
- Galactosemia (GALT; metabolic disorder affects ability to metabolize galactose)
- Hemophilia A and B (HEMA and HEMB; bleeding disorders)
- Hereditary Hemochromatosis (HFE; excess iron storage disorder)
- Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease)
- Marfan Syndrome (FBN1; connective tissue disorder; tissues of ligaments, blood vessel walls, cartilage, heart valves and other structures abnormally weak)
- Mucopolysaccharidosis (MPS; deficiency of enzymes needed to break down long chain sugars called glycosaminoglycans; corneal clouding, joint stiffness, heart disease, mental retardation)
- Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy)
- Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers)
- Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet)
- Polycystic Kidney Disease (PKD1, PKD2; cysts in the kidneys and other organs)
- Adult Polycystic Kidney Disease (APKD; kidney failure and liver disease)
- Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death)
- Sickle cell disease (SS; blood cell disorder; chronic pain and infections)
- Spinocerebellar ataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech)
- Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children)
- Tay-Sachs Disease (TS; fatal neurological disease of early childhood; seizures, paralysis)
- Thalassemias (THAL; anemias - reduced red blood cell levels)
- Timothy Syndrome (CACNA1C; characterized by severe cardiac arrhythmia, webbing of the fingers and toes called syndactyly, autism)
Currently in the
Does insurance cover genetic testing?
In most cases, an individual will have to contact his or her insurance provider to see if genetic tests, which cost between $200 and $3000, are covered. Usually insurance companies do not cover genetic tests, those that do will have access to the results. Insured persons would need to decide whether they would want the insurance company to have this information. States have a patchwork of genetic-information nondiscrimination laws, none of them comprehensive. Existing state laws differ in coverage, protections afforded, and enforcement schemes. The National Conference of State Legislatures provides a listing of current legislation regarding genetic information and health insurance. The recent marketing of genetic test kits directly to consumers, may lead to an increase in demand for insurance coverage. See the Genetics and Health Insurance (PDF) policy brief from the National Conference of State Legislatures for more information.
What is gene therapy?
Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, it’s the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result.
Gene therapy is a technique for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes:
- A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common.
- An abnormal gene could be swapped for a normal gene through homologous recombination.
- The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function.
- The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.
How does gene therapy work?
In most gene therapy studies, a "normal" gene is inserted into the genome to replace an "abnormal," disease-causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patient's target cells. Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes.
Target cells such as the patient's liver or lung cells are infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state. See a diagram depicting this process.
Some of the different types of viruses used as gene therapy vectors:
- Retroviruses - A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells. Human immunodeficiency virus (HIV) is a retrovirus.
- Adenoviruses - A class of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans. The virus that causes the common cold is an adenovirus.
- Adeno-associated viruses - A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19.
- Herpes simplex viruses - A class of double-stranded DNA viruses that infect a particular cell type, neurons. Herpes simplex virus type 1 is a common human pathogen that causes cold sores.
Besides virus-mediated gene-delivery systems, there are several nonviral options for gene delivery. The simplest method is the direct introduction of therapeutic DNA into target cells. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA.
Another nonviral approach involves the creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cell's membrane.
Therapeutic DNA also can get inside target cells by chemically linking the DNA to a molecule that will bind to special cell receptors. Once bound to these receptors, the therapeutic DNA constructs are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options.
Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.
What is the current status of gene therapy research?
The Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale. Current gene therapy is experimental and has not proven very successful in clinical trials. Little progress has been made since the first gene therapy clinical trial began in 1990. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD). He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier.
Another major blow came in January 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. FDA took this action after it learned that a second child treated in a French gene therapy trial had developed a leukemia-like condition. Both this child and another who had developed a similar condition in August 2002 had been successfully treated by gene therapy for X-linked severe combined immunodeficiency disease (X-SCID), also known as "bubble baby syndrome."
FDA's Biological Response Modifiers Advisory Committee (BRMAC) met at the end of February 2003 to discuss possible measures that could allow a number of retroviral gene therapy trials for treatment of life-threatening diseases to proceed with appropriate safeguards. In April of 2003 the FDA eased the ban on gene therapy trials using retroviral vectors in blood stem cells.
What factors have kept gene therapy from becoming an effective treatment for genetic disease?
- Short-lived nature of gene therapy - Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy.
- Immune response - Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a potential risk. Furthermore, the immune system's enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients.
- Problems with viral vectors - Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient --toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease.
- Multigene disorders - Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer's disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy. For more information on different types of genetic disease, see Genetic Disease Information.
What are some recent developments in gene therapy research?
· Results of world's first gene therapy for inherited blindness show sight improvement. 28 April 2008.
Previous information on this trial (May 1, 2007): A team of British doctors from Moorfields Eye Hospital and University College in London conduct first human gene therapy trials to treat Leber's congenital amaurosis, a type of inherited childhood blindness caused by a single abnormal gene. The procedure has already been successful at restoring vision for dogs. This is the first trial to use gene therapy in an operation to treat blindness in humans. See Doctors Test Gene Therapy to Treat Blindness at www.reuters.com.
- A combination of two tumor suppressing genes delivered in lipid-based nanoparticles drastically reduces the number and size of human lung cancer tumors in mice during trials conducted by researchers from The University of Texas M. D. Anderson Cancer Center and the University of Texas Southwestern Medical Center. See Dual Gene Therapy Suppresses Lung Cancer in Preclinical Test at www.newswise.com (January 11, 2007).
- Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, successfully reengineer immune cells, called lymphocytes, to target and attack cancer cells in patients with advanced metastatic melanoma. This is the first time that gene therapy is used to successfully treat cancer in humans. See New Method of Gene Therapy Alters Immune Cells for Treatment of Advanced Melanoma at www.cancer.gov (August 30, 2006).
- Gene therapy is effectively used to treat two adult patients for a disease affecting nonlymphocytic white blood cells called myeloid cells. Myeloid disorders are common and include a variety of bone marrow failure syndromes, such as acute myeloid leukemia. The study is the first to show that gene therapy can cure diseases of the myeloid system. See Gene Therapy Appears to Cure Myeloid Blood Diseases In Groundbreaking International Study at www.cincinnatichildrens.org (March 31, 2006).
- Gene Therapy cures deafness in guinea pigs. Each animal had been deafened by destruction of the hair cells in the cochlea that translate sound vibrations into nerve signals. A gene, called Atoh1, which stimulates the hair cells' growth, was delivered to the cochlea by an adenovirus. The genes triggered re-growth of the hair cells and many of the animals regained up to 80% of their original hearing thresholds. This study, which many pave the way to human trials of the gene, is the first to show that gene therapy can repair deafness in animals. See Gene Therapy is First Deafness 'Cure' at NewScientist.com (February 11, 2005).
- RNA interference or gene silencing may be a new way to treat
- New gene therapy approach repairs errors in messenger RNA derived from defective genes. Technique has potential to treat the blood disorder thalassaemia, cystic fibrosis, and some cancers. See Subtle Gene Therapy Tackles Blood Disorder at NewScientist.com (October 11, 2002).
- Gene therapy for treating children with X-SCID (sever combined immunodeficiency) or the "bubble boy" disease is stopped in
- Researchers at
- Sickle cell is successfully treated in mice. See Murine Gene Therapy Corrects Symptoms of Sickle Cell Disease from March 18, 2002, issue of The Scientist.
What are some of the ethical considerations for using gene therapy?
--Some Questions to Consider...
- What is normal and what is a disability or disorder, and who decides?
- Are disabilities diseases? Do they need to be cured or prevented?
- Does searching for a cure demean the lives of individuals presently affected by disabilities?
- Is somatic gene therapy (which is done in the adult cells of persons known to have the disease) more or less ethical than germline gene therapy (which is done in egg and sperm cells and prevents the trait from being passed on to further generations)? In cases of somatic gene therapy, the procedure may have to be repeated in future generations.
- Preliminary attempts at gene therapy are exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?
Genetic counselors are health professionals with specialized graduate degrees and experience in the areas of medical genetics and counseling. Most enter the field from a variety of disciplines, including biology, genetics, nursing, psychology, public health, and social work.
Genetic counselors work as members of a healthcare team, providing information and support to families who have members with birth defects or genetic disorders and to families who may be at risk for a variety of inherited conditions. They identify families at risk, investigate the problem present in the family, interpret information about the disorder, analyze inheritance patterns and risks of recurrence, and review available options with the family.
Genetic counselors also provide supportive counseling to families, serve as patient advocates, and refer individuals and families to community or state support services. They serve as educators and resource people for other healthcare professionals and for the general public. Some counselors also work in administrative capacities. Many engage in research activities related to the field of medical genetics and genetic counseling.
Societal Concerns Arising from the New Genetics
Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others.
Who should have access to personal genetic information, and how will it be used?
For more on this topic, see the Privacy and Legislation page in this ELSI suite.
Privacy and confidentiality of genetic information.
Who owns and controls genetic information?
For more on this topic, see the Privacy and Legislation page in this ELSI suite.
Psychological impact and stigmatization due to an individual's genetic differences.
How does personal genetic information affect an individual and society's perceptions of that individual?
How does genomic information affect members of minority communities?
For more on this topic, see the Minorities, Race, and Genetics and Genetic Anthropology, Ancestry, and Ancient Human Migration pages in this ELSI suite.
Reproductive issues including adequate informed consent for complex and potentially controversial procedures, use of genetic information in reproductive decision making, and reproductive rights.
Do healthcare personnel properly counsel parents about the risks and limitations of genetic technology?
How reliable and useful is fetal genetic testing?
What are the larger societal issues raised by new reproductive technologies?
For more on this topic, see the Gene Testing page in this ELSI suite.
Clinical issues including the education of doctors and other health service providers, patients, and the general public in genetic capabilities, scientific limitations, and social risks; and implementation of standards and quality-control measures in testing procedures.
How will genetic tests be evaluated and regulated for accuracy, reliability, and utility? (Currently, there is little regulation at the federal level.)
How do we prepare healthcare professionals for the new genetics?
How do we prepare the public to make informed choices?
How do we as a society balance current scientific limitations and social risk with long-term benefits?
For more on this topic, see the Gene Testing and Gene Therapy pages in this ELSI suite.
Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease) linked to multiple genes and gene-environment interactions.
Should testing be performed when no treatment is available?
Should parents have the right to have their minor children tested for adult-onset diseases?
Are genetic tests reliable and interpretable by the medical community?
For more on this topic, see the Gene Testing and Gene Therapy pages in this ELSI suite.
Conceptual and philosophical implications regarding human responsibility, free will vs genetic determinism, and concepts of health and disease.
Do people's genes make them behave in a particular way?
Can people always control their behavior?
What is considered acceptable diversity?
Where is the line between medical treatment and enhancement?
For more on this topic, see the Behavioral Genetics page in this ELSI suite.
Health and environmental issues concerning genetically modified foods (GM) and microbes.
Are GM foods and other products safe to humans and the environment?
How will these technologies affect developing nations' dependence on the West?
For more on this topic, see the Genetically Modified Foods page in this ELSI suite.
Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials.
Who owns genes and other pieces of DNA?
Will patenting DNA sequences limit their accessibility and development into useful products?
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