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Perspectives |
1 From the Department of Radiological Sciences, University of California, Irvine Medical Center, Orange. Received April 3, 2002; accepted April 8. Address correspondence to the author, 18961 Castlegate Ln, Santa Ana, CA 92705 (e-mail: rmfriede@uci.edu)
Index terms: Ethics, medical • Genes and genetics • Perspectives
With the completion of the Human Genome Project and the potential for detecting hundreds of genetic abnormalities on the horizon, it would appear to be a good time to pause and consider how this genetic juggernaut is to be controlled. Although many potential benefits may result, there will be numerous problems that must be considered. Should genetic testing be provided in commercial markets? Should it be provided by physicians? Should the consumer have the final say? Should the insurer determine what should be done, or is it necessary for society to oversee what is allowable?
It would appear that the ability of the medical profession to provide information regarding genetic testing is light-years ahead of the community coming to grips with the moral issues. Should we mandate screening to detect severe anomalies warranting termination of pregnancy? Would forcible genetic screening be an arrogant intrusion on patients’ rights, or is it justified if we can eliminate severe debilitating and fatal diseases as both a public health and economic consideration? What constitutes a serious disease? At the Shriver Center in the United States (1), it was found that different groups rated the same disease as serious or not serious. Who should decide? Handicapped organizations have emphasized the "right to abnormality," suggesting that abnormalities may be creative and enriching (1). Individuals should theoretically have the right of choice, but are they capable of making an informed decision? Are there public health and societal rights that must be considered? The morality of genetic testing or screening has been debated in the literature, but standards have not been set, and moral issues are frequently skirted. It is not a topic that most politicians like to consider.
In this article, I will try to present some of the ethical problems associated with genetic testing and let you judge where the line should be drawn. As you will see, there are many more questions than answers.
Genetic screening was defined by the Danish Council of Ethics in 1993 as the study of the occurrence of a specific gene or chromosome in a population or population group in which there is no previous suspicion that any given individual has the condition (1); in effect, you are dealing with an unknown population. Complicating the matter further, within the general population, there are subgroups that might undergo screening, such as neonates, children, adults, and fetuses, and the ethical issues might well be different in each group.
In contrast to screening, testing applies to an individual in whom there is some reason to think he or she may be at risk for disease. Obviously, there may be overlap between the two groups. Genetic screening or testing, which some consider a form of preventive medicine, may have enormous future potential but also has enormous, complex ethical and legal problems. Wald (2) believes that the expectation that genetic screening will be able to reliably detect numerous diseases is probably unfounded. Genetic markers of a disease are, in most instances, too insensitive and nonspecific for screening purposes, and many individuals with the disease will not have the marker, while many with the marker will not develop the disease. In any individual with a marker for a given disease, the risk of developing the disease is usually uncertain. Therefore, screening for genetic diseases will be much like screening for other lesions, with many indeterminate results. There may be many different genetic mutations for a disease, with any one of them accounting for only a small percentage of the total cases, so it may become impractical and expensive to test for many of these diseases. Wald (2) believes that a better approach is to attempt to develop a test that measures an early biochemical or other manifestation of a genetic disease, because this sort of test would be simpler, less expensive, and more effective in identifying individuals who may develop the overt disease. This is true, for example, in neonatal biochemical screening for phenylketonuria and in blood screening for sickle cell disease (2).
Eugenics is defined in Stedman’s Medical Dictionary as a term that denotes practices and policies that tend to better the innate qualities of man (3). The term was coined by Frances Galton in England at the end of the 19th century to represent the science that deals with all factors that improve the qualities of our race (4). Charles Darwin gave impetus to eugenics with his theory of evolution by means of natural selection, which tends to weed out weaker varieties (5). When we breed racehorses, we breed those with the best qualities to produce champions. Should we maintain the integrity of our unaltered species to preserve our heritage, or should we attempt to apply eugenics to reduce fatal and disabling diseases to improve the characteristics of the human race? If we use genetic engineering, we do not know the long-term effects, and, of course, we cannot control genetic mutations, which are unpredictable. Genetic testing is presently being used in some countries for couples prior to marriage or for containment of population growth (5). Most countries, for example, offer prenatal screening for Down syndrome to women over the age of 35 (1).
Romeo-Casabana (5) divides the science of eugenics into two groups: positive eugenics, defined as the promotion of desirable traits, and negative eugenics, defined as the avoidance of the transmission of undesirable traits. Selection of marriage partners or specific semen for fertilization are examples of positive eugenics, while genetic engineering to prevent Huntington or Tay-Sachs disease are examples of negative eugenics. It would appear that negative eugenics could be more popular, since the purpose is to decrease the incidence of diseases that lead to serious disability and early death. However, negative eugenics, which are used today in animal breeding, also include such procedures as sterilization, contraception, and abortion. Actually, in the first third of the 20th century, some 30 states had laws regarding negative eugenics, involving matters such as restricted marriages, immigration, and sterilization (5). Although negative eugenics lost credibility after the 1930s, the point of interest is that democratic governments had passed such laws prior to that time.
In genetics, which is a somewhat different field than the rest of the medical profession, the aim is not to cure but to provide information for individuals to make decisions regarding their lives. The duty to avoid harm overrides the duty to help, and screening has the potential to harm both individually by raising anxiety and socially by creating genetic discrimination. The right to know the result of a genetic test is obvious, but is there also a right not to know? The concept that the individual has the right not to know is complex, since the information is relevant not only to that individual but to family members. Does society have the right to know in instances in which undesirable social effects may ensue? Individuals may not wish to undergo testing because results may lead to discrimination regarding matters such as insurance or employment. However, the results of testing may be important to relatives and to the public, who may have a responsibility to know. If information is disseminated, can society protect these individuals against stigmatization and discrimination?
Since genetic disorders are family disorders, it is women who will assume the greatest role in managing them (1). Women will be more likely to request screening and encourage other family members to take part and may assume the main burden of responsibility for decisions concerning prenatal screening. Women usually assume a greater responsibility for any long-term commitment required by a child born with a genetic disorder.
There are three main approaches to gene therapy: counseling, abortion, and gene manipulation. Counseling can be implemented prior to both testing and screening and may serve as an aid when deciding on further action in cases of a positive result. Abortion relates to natal screening and germ-line gene therapy, while gene manipulation relates to both somatic and germ-line therapy.
Crisp (6) makes a sharp distinction between somatic cell gene therapy and germ-line gene therapy. Somatic cell gene therapy implies that a patient is treated genetically for a condition without it affecting his or her reproductive potential. Germ-line gene therapy does affect a person’s gametes, and any changes affect future generations. Therefore, it is easier to accept somatic cell gene therapy than germ-line gene therapy. With germ-line gene therapy, many people object to genetic screening and testing, since it will affect procreation, and, following identification of affected embryos, lead to abortion. Many believe that a fetus with Huntington disease could have a useful life, although short, and that the fetus does not deserve to die. They do not accept the argument that abortion would allow the individual to have a second fetus that might be normal, because this scenario is irrelevant to the first fetus, which will have never lived. These individuals believe that we have no right to judge the quality of life of the first fetus and terminate its life.
Crisp (6) also makes the distinction between negative and positive genetic engineering, similar to Romeo-Casabana (5). Negative engineering is an attempt to remedy defects, while positive engineering is an attempt to create improvements. Curing blindness is an example of negative engineering, while making an individual more intelligent is an example of positive engineering. Again, people are happier with negative rather than positive genetic engineering.
Crisp (6) notes that those who believe that scientists who perform genetic engineering are playing God are actually objecting to what they consider scientific arrogance. They object to interference with our natural heredity, which leads to the variations seen in the human race. One can carry this reasoning forward and consider that it is arrogant to treat pneumonia with antibiotics or perform organ transplants, which interfere with the natural order of life. John Mackie, an English philosopher, pointed out that if this type of engineering had been possible in the 19th century when religion was foremost, everyone would now be intolerably pious and chaste (6). Although this is a simplification, so-called scientific arrogance can be controlled and should not be a major factor in determining the value of genetic screening.
A more important problem is the concept of the "slippery slope," which is present in many areas of research. Is it possible that in the future we could decide that a certain skin color is a disorder and should be corrected? Would we allow selection of sex, hair color, or height in embryos, or state that myopia is a substantial disorder and that everybody should have 20/20 vision? We state that we will only correct serious and disabling disorders, but who is to determine what is serious, and how does one keep this matter from sliding into frivolous and perhaps objectionable categories?
As of 1999, more than 4,000 disorders were identified as likely being linked to specific sites or specific chromosomes. There are genetic tests for nearly 700 inherited disorders, of which more than 300 tests are available in a clinical setting, and more are becoming available all the time (7,8). Some of the major areas of genetic screening here or on the horizon include Alzheimer disease, Huntington disease, Parkinson disease, Tay-Sachs disease, cystic fibrosis, and tendencies regarding alcoholism, heart disease, and colon, breast, and ovarian cancer (9). Should everyone or only women at high risk have access to prenatal testing? Should all women or only those at high risk be offered testing for the genes implicated in breast and ovarian cancer? Who should pay for these tests? Are there any tests that society is prepared to forbid? Should genetic screening become part of an individual’s physical examination? It might be plausible to perform a selected battery of screening tests once during childhood. Such a test series might become a routine part of a physical examination and would require discussion only if results were abnormal. Obviously, increased genetic testing will relate to the overall allocation of health care funds to preventive medicine.
Some believe that if we have the ability to identify serious disorders in children or fetuses, we then have a responsibility to do so, and not to do so becomes irresponsible. Andre et al (10) believe that the judgment of irresponsibility is an individual perspective. There is a space between responsibility and irresponsibility, just as there is between like and dislike, which we frequently term the "gray area," something between black and white. Individuals may have different perspectives as to what is responsible or irresponsible. Is it irresponsible to be a single mother, a welfare mother, or a teen mother? There will be much disagreement about what represents responsible genetic testing.
In considering the host of genetically testable disorders, there is a considerable difference between those disorders that occur early in life and those that occur later in life. Genetic disorders occurring in adult life can be transmitted to future fetuses, while those that are fatal in children can only continue if they are genetically recessive or if they are genetic mutations. There is also a considerable difference between genetic disorders, which imply that you will almost certainly get the disease, and disorders in which genes increase your vulnerability to a disease, such as colon or breast cancer, in which the development of disease is by no means inevitable. When considering where future efforts should be directed, all of these factors must be taken into consideration.
Genetic research has been approached warily by religious organizations. Bishop Friend (11), who was Chairman of the U.S. Bishop’s Committee on Science and Human Nature in 1995, stated that the human genome initiative will be a great force for the good of humankind. However, he believed that we should not modify the human genome in ways that could alter the nature of a person and that we must not confuse our technical expertise with moral authority. He believed that experimentation should be limited so that gene transfer is used only for the treatment of serious diseases, not for any prevention of disease or other eugenic purpose. Chromosomal or genetic manipulation to influence inheritance, which is not therapeutic, is contrary to personal dignity. Various religious groups are closely watching the progress of genetic experimentation and will try to influence regulations regarding types of genetic manipulations, which may become permissible.
The public, our politicians, and much of the medical fraternity have little knowledge of genetic screening or testing. Their decisions will be influenced by religious societies, medical societies, medical-related industry, and the media. McCombs and Shaw (12) believe that media coverage may have the greatest effect on public opinion. While the media may not be able to affect what we think, the media is very successful in telling us what to think about. The amount of media coverage has considerable influence on our perception of the important problems facing America (13). The media, especially television, influence what issues the public is concerned about, and the way issues are presented in the media can influence public perception and attitudes (14). It would appear that media coverage of genetic testing and screening may have a major effect on the public’s concept of what should or should not occur.
A major problem with genetic testing or screening is the conflict between allowing individual autonomy and dealing with possible public health consequences of the sum of these personal choices and how they will affect our society (15). There are four groups of people who may want or need to know about our genetic composition (16): first, ourselves; second, our families and reproductive partners; third, individuals and groups with whom we have contracts and economic arrangements, such as employers, employees, and insurance companies; and fourth, society, since our health status can influence our contribution to society and the amount of care we might need. Takala and Gylling (16) believe that in liberal countries, society cannot force people to undergo genetic testing, except in cases in which the information is necessary to avoid harm to others. Although it might be useful for an individual to know of his or her hereditary problems so that one could draw a life plan and perhaps improve one’s environmental status to minimize the genetic problem, it may be unkind to force people to have knowledge of the condition if it is incurable. Of the four groups who want or need to know, obviously the prime group is the individual, followed by the reproductive partner, family, and society. It would seem logical that for genetic diseases, which have a high probability of incidence and which are fatal or produce serious disability, the need to know extends to families and society. When such a list is agreed on by public health and medical societies, perhaps a one-time population test at a given age could be performed as a universal screen.
The question of fetal testing and abortion is a much more difficult problem. Should we terminate a fetus with a serious genetic problem? Some argue that even a life that contains suffering is better than no life at all. Are we wrong in denying potential individuals the chance to live? There is a strong argument that individuals should be free to make unrestrained life and reproductive choices. But, these choices will have a cumulative effect on society, and controls will be necessary.
In the near future, with the proliferation of genetic information, medical corporations will likely offer genetic testing on a for-profit basis. Advertising and media information may cause people to use genetic testing indiscriminately. Since genetic testing and screening will have long-term societal effects, societal controls are necessary, and they must be established soon. A task force of the National Institutes of Health in 1997 recommended that a federally chartered advisory committee on Genetics and Public Policy be created to include the various stakeholders involved in genetic testing (8). They believed that the public is not being adequately protected from genetic tests that have not been adequately validated and for which clinical usefulness has not been established.
Hoedermackers (17) believes that the introduction of predictive genetic testing services should be determined by a permanent national overseeing body, involving all interested parties, suppliers, health professionals, and consumers. This body must make the difficult decisions concerning where the line should be drawn between normality and abnormality, since genetic manipulation will have biologic, psychologic, and psychosocial effects on society. There are many variations and difficulties in predicting normality and abnormality. Hoedermackers (17) believes that a national rather than international overseeing body is necessary because of national differences in health care systems and budgets, insurance systems, and priorities.
Iles (15) believes that a coordinated international approach, rather than a national approach, is essential for several reasons. Genetic testing will affect institutional structures and social practices in many countries with divergent cultures. We need an international effort to ensure the uniformity of standards and prevent abuses of genetic information, which are likely to occur in countries that lack strong human rights cultures and in countries in which society is controlled by dictatorships. He believes that there must be some limitations on the rights of individuals to make genetic decisions: First, the decision must not impinge adversely on the rights of others, and second, it must not have major social consequences. Private corporations can affect the pattern of genetic testing by what they release into the market and by inducing physicians and consumers to move toward genetic screening and therapy. Because of these many factors, controls must be imposed, and Iles believes that an international covenant should be developed.
As promised, I have offered many questions and a few suggestions, leaving you to decide the answers. The heritage, background, and education of individuals influence their opinions. The difficulty in establishing controls at present is compounded by the fact that genetic screening is too new and that long-term effects of genetic interference are unknown.
I believe that genetic researchers should be cautious, and that it is necessary to start to develop oversight and controls now. International oversight is important to correlate and help control what is happening and what will happen. We are considering changes that will affect the future makeup of the human race, and this matter is beyond national controls, which may vary from country to country. If national pride mandates that each country formulate its own rules, let us at least agree on what should not be done. My tentative opinion certainly supports genetic testing in pregnancy and genetic screening in population groups with a previous genetic history. The diseases for which screening is permissible should be approved by an oversight commission.
I am aware of the problems introduced by a bureaucracy, but the potential of creating a slippery slope in the application of genetic research, where huge profits might be obtained, will be too tempting to many to allow unsupervised research.
We are in the midst of a revolution in medical care that may provide huge benefits to the next generation.
What you have before you go into the woods is innocence. What you have in the woods is experience. What you find in the woods is knowledge (18).
Let us take full advantage of the knowledge we can obtain, but let us proceed carefully.
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