For clarity I will divide the ethical issues
and dilemmas into those which are dependent upon the technique,
those which depend upon the time of gestation that it is being
offered; those dependent upon the disease severity, gene penetrance,
or ability to be treated, those which may have particular cultural
and social peculiarities, and those involved with the social choices
to allow prenatal diagnosis. First we can ask what is bioethics?
Bioethics and the History of Genetics
"Bioethics" means the study of ethical issues arising from human involvement with life, and I have called it simply the "love of life" (1). Love is a broad term, but includes the concepts of balancing benefits and risks. Love is the desire to do good and the need to avoid doing harm. It includes love of others as oneself, and respect of autonomy. It also includes the idea of justice, loving others and sharing what we have - distributive justice. It includes love for oneself and one's family, love for other people, love for the environment around us, and love for God. These concepts of bioethics are found in ancient writings around the world - both as descriptions of behaviour and as prescriptions that others have made on the desirable standards of individual choices, and of society.
There are three ways to think of the term bioethics, one is as descriptive bioethics - the way people view life and their moral interactions and responsibilities with living organisms in life. Another is prescriptive bioethics - to tell others what is good or bad, what principles are most important; or to say something/someone has rights and therefore others have duties to them (2). A third is interactive bioethics - the discussion and debate between different persons over these two types of bioethics. These concepts can be traced in religions and cultural patterns that may share some universal ideals. This is especially true when we talk of reproduction and genetics, themes of family, which have been discussed for millennia.
To illustrate the history of thought of both ethics and genetics we can think of Aristotle. His pioneering experimentation and philosophical interpretation lead him to the concept that there was a biological development of the early embryo through several intermediate stages of growth, considered first to be vegetative, then animal, and then at 40-90 days after conception, the human was sufficiently organized and disposed to be the recipient of the specifically human form, the rational soul (3). The influence and content of Aristotelian reproductive biology was very wide, and was made more influential in society because he developed his philosophical ideas from his descriptions of the natural world. The issue of when a human fetus becomes animated, ensouled, a person, or protectable, whatever term we prefer, remains a fundamental ethical issue in questions involving abortion. The specialization of modern science is only very recent. In the past the application of science and technology also raised ethical issues, but like today, not all considered these issues. Only some were aware of the social and ethical issues arising from their work, but the genetic counselor who takes the techniques out of the laboratory to real people and lives, should be confronted with these same dilemmas.
The origins of genetics also are often believed to be recent. People may believe that genetics as a science started with Mendel's experiments with the passing of parental characters in peas in the 1850s. However, the idea that characters or traits were passed from one generation to the next has been known for many millennium. The cross-breeding that produced agriculturally useful crops such as wheat or corn has a long history, as does the breeding of domestic dogs or cats from wild ancestors. The knowledge that interfamilial marriages lead to more handicapped children, and that blue eyed children come from blue-eyed parents is also very old (4). Aristotle believed that the female supplied the "matter" and the male the "motion" that would determine the child's characters. There are similar ideas in ancient manuscripts of other cultures also. However, Hippocrates and Galen, and Islamic writers later, believed that because both men and women produced semen they contributed equally to the process. In the nineteenth century in Europe, the human genetic traits were thought to be associated with blood. The physical location of the genes has only been determined since 1908, when Thomas Morgan identified the genes to be associated with parts of chromosomes. In 1911 Morgan and colleagues produced the first chromosome maps, and they spent many decades working on genetic studies in fruit fly. In the 1940's Avery showed that traits could be passed from one bacteria to another by a chemical called DNA. In 1953 the structure of DNA was determined to be a double helix and the science of molecular biology and genetics grew.
Out of this the possibilities for the powerful predictive powers and science of prenatal diagnosis developed. What is clear however is that the issues of genetic causation of human variation and genetic defects was not new. Prenatal diagnosis is now associated with normal prenatal care in most industrialized countries. There are some important non-genetic screening programs. For example, if a woman is not immune to rubella, she should be immunized before becoming pregnant. There are other infective hazards to the fetus, such as toxoplasmosis cytomegalovirus and herpes virus, which are also important for potential mothers to be immune to. If we look at the reasons given for introduction of prenatal diagnosis in the 1970s the most common reasons were genetic counseling removes anxiety of mothers, it reduces the number of children born with certain diseases, and increases the economic advantages to society (5).
One of the common events across all cultures is the birth of a child, and the development of a family. Genetic disease has meant that some people face the trauma of a handicapped child, and genetic variation means that society has to be mixed. When people talk of the "new" genetics, as an example of new technology, they often forget the fact that their ancestors also thought of genetics and having children who would lead a healthy life, otherwise they would not be here (4). Because of these deeper origins, I would argue there is no inherent clash between genetic technology and ethics, and we should reject the phrase "Genethics" (6) because almost all the issues raised by application of genetics are not novel (7).
We can see early images of genetic disease in the sculptures found in ancient cultures, and the stories. For example the concept of Mabiki in Japan (in which handicapped babies were left to die or killed, the word means thinning out the newly planted rows of seedlings), is something seen in most cultures in the past. The question of how a sick baby should be left to die is one which may be becoming less familiar to modern people in developed countries, actually converse to the idea that genetics is giving us more dilemmas. We luckily can treat more sick patients than we could in the past. Though, it is true that use of life-sustaining technology gives us more questions about when to stop the respirator, and when to stop applying medicine. Sometimes we wonder whether our technology offers us too much, but prenatal diagnosis can provide a way out of the anxiety that parents feel when they know they are at risk for such a future tragedy. It is also true that although new medicines and genetic treatment have the potential to decrease the number of us that die early because of genetic disease, it means that more of us will die of late onset genetic diseases, which could be a new issue.
Ethics deals with decision-making, about making good choices, and choices that we can live with, improving our life and society. The timing of reproduction, contraception, marriage choice, or euthanasia are not new choices, but are always difficult. What principle do we rely upon the most in making ethical judgments? As discussed above under the word "love", we could use the principles, autonomy, justice, beneficence and do no harm (non-maleficence) (8). One of the dilemmas in choices is balancing between autonomy of the individual making the choice and protecting the autonomy of others, which we could term love for others. Joseph Fletcher proposed the theory of Situation Ethics in 1966 (9). He said love was the greatest principle in bioethics. He was rewording a form of the Golden Rule, "love others as yourselves", which has been passed down in religion for 3,500 years.
Recently individual autonomy has been the most valued principle, and has often been over-valued I believe. If we respect the autonomy of human beings we respect their right to have at least some property, and to have control over their own body. This is international law, and has a good effect in many parts of the world, protecting the weak. When we apply to prenatal diagnosis some advocate the mother's autonomy allows her to decide. However, our autonomy should be limited by respect for the autonomy of other individuals in the society. Individual's well-being should be promoted, and their values and choices should be respected, but equally, which places limits on the pursuit of individual autonomy. We should give every member in society equal and fair opportunities, this is justice. Society should also include the future of society, future generations are also an essential part of society. If prenatal diagnosis is linked to selective abortion then we may consider that the autonomy of the fetus could lead us to a conflict.
These dilemmas bring us to look at the concept of balancing the best interests of the individual or family. Autonomy should not be the most valuable principle of bioethics, even if it is the most dominant feature of human behaviour (e.g. selfishness). If it is we arrive at a society with lack of concern for the poor and sick. Instead, we need to balance selfishness with sufficient altruism, to make a true loving society. We can refocus our concerns to consider the best interests of the individual and the family, not only the autonomy of the individual. The danger of using this language is paternalism.
We have now arrived at a case-centred approach
to the ethical dilemma, considering each case in terms of the
best interests of the mother and the fetus, in a family. In the
rest of this chapter we will look at some issues which affect
the way we may determine the ethics of a case, and some issues
which may be raised with the mother and family in the process
of genetic counseling. Whether we use principles to make decisions,
for example, non-medically indicated sex selection is always wrong,
or apply rules to cases, for example, we should only perform selective
abortion if the mother requests it for medical indications after
counseling in what is considered the best interests of the fetus
and mother, we are still left with a the ethical issue of prenatal
diagnosis. That is should there be counseling, and should that
counseling be directive or non-directive?
Ethics of Counseling
Genetic counseling is the process of conveying risk information about genes. Definitions of genetic counseling agree that it is the communication of information about diagnosed genetic conditions, in a way that allows the persons to make as autonomous decision as possible from that information, while safeguarding the emotional and ethical character of the person who asks for the conclusion (10). Chadwick (11) defines genetic counseling as (a) advising adults preconception, of the probability of their conceiving a child who will suffer from a genetic disorder and (b) advising adults, post-conception, by the use of some method for fetal screening, as to whether or not a fetus is suffering from a genetic disorder and (c) alerting adults to their options. This is what we could call non-directive counseling. Clarke (12) includes the following activities under the term genetic counseling: (a) The achievement of an early, precise diagnosis of the condition causing concern; (b) The screening for complications of genetic disease, thereby assisting in the management of affected individuals; (c) The provision of social and practical support for those individuals and families; (d) The development and application of specific therapies for genetic disorders. It is a wider scientific definition.
Most authors consider that non-directive counseling is preferable to directive. In practice, however, surveys suggest that there is considerable range on the extent of directiveness in the practice of counseling in different countries, and between them (13). The difficulties expressed include how to ensure that verbal and nonverbal cues remain nondirective, when to recommend further testing, when the client is unable to understand the information, when a better choice is clear and to recommend medical care or counseling, or when a client has difficulty making a decision (14). Despite several decades of experience with the psychological aspects of prenatal diagnosis (15), further research to study the impact of, and extent that decisions are informed, is still needed to assess the best method of counseling (16).
Counseling relies on adequate understanding of the risk and information about the disease (17). It is often difficult for many people to grasp the exact meaning of probabilistic information because of emotional barriers (18). Some interpret 1 percent risk as high and others interpret 10 percent risk as low. In surveys in different countries, there are wide variations in the concept of risk (1). Studies suggest that unrealistic optimism of genetic risk is not related with personal experience with the risk (19). This is part of the human side of counseling. In a US study of the proportion of women who would use selective abortion when the chances of the diagnosis being correct increased, it was found that there was a 50 percent increase in the number who would abort the fetus if the probability of the fetus having a serious neural tube defect increased from 95 to 100 percent (20). This view of certainty versus high chance, a 19 in 20 chance, is interesting. The perception of what constitutes a serious risk varies between patient and counselor. It has something to do with the type of optimism that we have for things to turn out all right. Other factors found among women who favour selective abortion are those with higher education, those who wanted fewer children, those who had a previous abortion, and those who attended religious services less often. Women who were in the screening program had a similar attitude to those who were not. Between 60-90 percent were in favour of selective abortion, depending on the seriousness of the disease.
Ethically we can say that are trying to benefit the person, but how do you measure success in prenatal diagnosis. There may not be a correct decision, but I suggest that a good decision is one that is made after thorough consideration of the information, and one that the person can live with afterwards. One measure of success is the workload (12), another is the person's satisfaction with the service and the reasons given for choice (13), although success also consists in the fact that the individual makes choices. The ideal decision-making may involve these families and the opinions of relatives. The process of counseling has been found to have generally positive psychological effects on the families involved, even when they do not remember the risk details (21).
Under what situations is directive counseling justified? One case is for clients with mental diseases or who cannot make decisions themselves. If their partner or family is unable to help or considered not to be acting in the patient's best interests, there is a case for the counselor to seek advice of both colleagues and third parties who may be able to confirm, refine or reject the counselor's decision. Human rights laws require that a women should never have an abortion against her will. There are differences under national laws in the reverse case, when a woman should not be allowed an abortion. However, there may be cases in which a physician should provide further information or contacts for a woman to understand the likely condition of her future baby, whether it is lighter or heavier in severity than her image. Although in countries that allow it, more pregnant mothers decide to abort a handicapped fetus, surveys discussed later in this chapter find that among families with disease about one-half decide to keep the fetus.
In a major international survey of genetic counseling (13), it was found that non-directive approaches are preferred by more than 90 percent of the counselors. This widespread acceptance of non-directive counseling means that they act as "decision-facilitators", providing information and leaving decisions up to the patient's autonomy. There is a more directive approach seen in East Germany, Hungary, or India, where they see it more important to give more advice and guidance (22). It has been suggested that the non-directive counseling has been a feature of genetic counseling because it was primarily scientists who developed the services, who unlike physicians, are not in the habit of giving directive advice (23). However, although it is accepted that non-directive counseling is required to respect the autonomy of the different people who use the services, many patients, in any country, do expect guidance when making up their minds on difficult questions, and it is not easy in practice to be fully non-directive (24).
From the survey of Wertz and Fletcher (13) several other concerns were expressed by geneticists. These concerns in order of priority were as follows:
1) Fairness of access to genetic services
2) Abortion choices, and legal restrictions
3) Confidentiality problems
4) Protecting privacy from institutional third parties
5) Disclosure dilemmas
6) Indications for prenatal diagnosis
7) Voluntary or mandatory screening
8) Counseling incapacitated persons
The survey is important because it shows the order of priority from the standpoint of practicing geneticists. From these factors, a code of ethics was drafted and proposed (25).
Because of the explosion of information and possibilities that will be upon us soon, there are calls for a code of ethics of medical genetics to be debated and established, and the World Health Organization has issued guidelines (26). Included in these guidelines are the idea that "all individuals should have a right to know their genetic risks and risks to their potential offspring; to be educated about these risks, and to have the services available to act upon the knowledge, including the option of safe, accessible termination of pregnancies with affected fetuses if desired by prospective parents." Although there must be international discussion, would it be possible to give the power to any committee or authority outside the existing national medical boards to sanction those who are unethical? Those favoring a code consider that medical geneticists should become more professional in the sense of setting a written ethical code that members must follow. Until now, the arguments are either oral or else in the literature. Other reasons for a written code include the fact that geneticists would be more publicly accountable and their views may be more considered in public policy. A code also enables the moral commitments of this generation to be transmitted to the next generation, which is the background for the UNESCO Declaration on the Human Genome and Human Rights (27) which was approved in 1997.
What seems to be the critical question is
whether such a code would aid the situation, and in many countries
of the world there is no code available, so it probably would
be beneficial. During the process of debate on declarations or
codes people also become more aware of the ethical issues, on
a broader scale than their daily practice experience. Whether
or not there is a new code, the issues come back to the relationship
between the counselor and the client(s). The issue ultimately
comes to the health of families (28). The point of counseling
is to help persons and families make good decisions for their
future well-being, health in the broadest sense.
Ethics, screening and selection
First we can ask "Are there intrinsic ethical issues which arise from the act of screening or selection?" A feature of good medicine is prognosis, the prediction of the course of disease. Some type of screening may be required before any medical decision. The particular techniques have been discussed in the previous chapters of this text. The physical screening of protein or genetic abnormality may allow detection of a disorder before there are any physical signs of it, or even before a gene is expressed if it acts later in life. Genetic screening is the testing of genetic variation, the same as we may screen people according to their weight.
For every medical procedure the patient should be offered an explanation of the problem and possible solutions, and then their consent should be obtained. This is called informed consent. The information includes at least the following, which must of course, be presented in language the patient can understand (29):
1. A description of the recommended treatment or procedure
2. A description of the risks and benefits of the recommended procedure, with special emphasis on risks of death or serious bodily disability
3. A description of the alternatives, including other treatments or procedures, along with the risks and benefits of these alternatives
4. The likely results of no treatment
5. The probability of success, and what the physician means by success
6. The major problems anticipated in recuperation, and the time period during which the patient will not be able to resume his or her normal activities
7. Any other information generally provided to patients in this situation by other qualified physicians
Responsibility for deciding to undergo screening may be a burden for the client and the provider, but we must seek it otherwise autonomy and democracy will break down. We must make decisions even if they are a bit complicated. Health care workers need to make patients to make decisions, we must find the best way to do this, as discussed above counseling skills are required. Health care workers should be decision facilitators, the patients should make the decisions.
We then can examine the criteria for a condition to be justified to enter a screening program. The condition should be an important health problem, the natural history of which should be adequately understood. There should be a policy agreed upon regarding whom to treat as patients, and a suitable screening test should be available. The cost of diagnosis and treatment of patients diagnosed should be economically balanced in relation to possible expenditure on medical care as a whole (30). The problem with cost analysis is how much to value the benefits to the people being screened, beyond medical costs of treatment versus prevention (31) . Prenatal diagnosis is special in the sense that informed consent is given not by the fetus but by a proxy, for the fetus (the parents and family). The client is the parents not the fetus, although the physician and parents may regard the fetus as the potential patient. It is also special in that there may be no therapy available, as discussed below.
Does it make an ethical difference whether we look at the enzyme or protein expression or a DNA sequence? Although screening of a DNA sequence is the most powerful method of providing information on the genotype, protein testing has often been cheaper, easier and it provides information on the phenotype that more directly affects the person.
DNA probes that are independent of family history are preferred technically as probes because no prior screening of the parents is necessary. They can be used for all pregnancies without a history of genetic disease. Many genetic diseases arise spontaneously in each generation and, therefore, would not be predicted. Ethically there is also an advantage that this avoids the need for obtaining consent from other family members for taking DNA samples. The parents who are carriers of recessive harmful alleles do not have to be screened and marked as carriers, which can have harmful psychological and social effects.
Prenatal diagnosis is normally considered during the time of pregnancy; however, some couples seek genetic counseling while planning a pregnancy. How far back in time should the knowledge of carrier status be sought and how early should such knowledge be given? Some genetic screening tests have been tried on large scale, such as those implemented by the 1972 US National Sickle Cell Anemia Control Act. This Act provided for research, screening, counseling and education concerning about sickle cell disease. About one in twelve American Negroes carries the allele for sickle cell anemia. There were serious social problems in implementing such a program, because it was seen by some as racist and aimed at slowing down the Negro birth rate. Fortunately the disease can now be treated, so that there are two medical options, one is abortion, the other clinical treatment. Sickle cell diseases (anemia, sickle cell-hemoglobin C and sickle cell-B-thalassemia) affect about 1 in 400 American black newborns.
The population testing conducted upon newborns using protein or enzyme based tests, with therapeutic options, can be distinguished ethically from genotype testing for carriers of genes for recessive disorders. It is recommended by numerous medical associations to have universal screening of all newborns for hemoglobin disorders. However, if a fetus or newborn is found, then the mother will be approached first, to consider whether the family should have screening. It is essential that education about screening programs is given in schools and in the mass media, and the genome project has provided an additional effort toward expansion of education programs in many countries.
The information obtained by population screening can be stored in a registry for later recall before marriage, which raises privacy concerns regarding storage. Some are in favour of such testing to protect the ignorant and to avoid "complicity in tragic birth" (32, 33). Ramsey (32) stated that he would approve of the use of the United States' marriage-licensing laws to prevent the transmission of very bad genes. Although it may be true that no one has an unqualified right to have children, it may not be right to approve of such law enforcement to prevent marriages. Using such laws is a dangerous step towards government enforced eugenics. It is important to maintain voluntary use of screening, if people are educated most will try to avoid having children with a genetic disease. Compulsion by law may turn people away from seeking aid and may make them suspicious of the technology in general (4).
If we do genetic testing before marriage there are many potential ethical problems, including privacy and stigmatization. Premarital testing can be used to exchange genetic information before marriage if people are concerned about possible genetic diseases in future children. It has been used successfully with Tay-Sach's disease among Ashkenazi Jews. Tay-Sach's disease is a rare genetic disease which affects the brain, causing a painful death by 3-4 years age. One in thirty Ashkenazi Jews carry the allele, a ten times higher level than in the general population. When both parents are carriers, the risk of their children being afflicted is one in four. Because it as prevalent in the Jewish community, there have been various screening programs used with the cooperation of the Community. The preference is to screen people before marriage, because the Jewish view is that it is better to prevent marriage than to use prenatal screening and abortion. Premarital testing is more widely accepted than selective abortion. Until 1990, the major motive for many people in Japan, especially women in their 20s, to seek genetic counseling was premarital testing (34).
There have been psychological problems with these screening programs, because carriers often are treated, and feel though they are outcasts. There also have been real benefits of reducing parental anxiety regarding their children and reducing anxiety for the adults themselves if they are screened and found not to have the disease. Experience suggests that such genetic testing can be performed successfully if extreme care is taken to protect individuals. However it is unlikely to apply to most societies, in which people fall in love without consciously considering their possible partner's genes.
We can learn about postmarital testing from some of the successful prenatal screening programs in high risk populations, for example the diagnosis of beta-thalassemia in Sardinia, Italy, in a Catholic environment in which we would have thought religious and ethical concerns about abortion would have prevented it. The 20 year program has been based on carrier and prenatal screening. The incidence of homozygous state is 1 in 250 live births in Sardinia, with a carrier rate of 1 in 8, meaning that approximately 1 couple in 60 are both carriers, at risk of having a homozygous child. The carrier screening program had detected 30,500 carriers and 1,544 at risk couples, by mid-1990 (35). Another 812 couples were known to be at risk because of an affected child, together 87 percent of the at risk couples in Sardinia knew their status. Approximately 90 percent of possible cases are now prevented by the use of prenatal diagnosis and selective abortion. The population of Sardinia is mainly Catholic, but fewer than 1 percent of the couples who were found to have an affected fetus decided not to have an abortion. The reasons for the residual cases of thalassemia were analyzed, and it was determined that 67 percent were because of parents' ignorance of thalassemia, 13 percent were because of mispaternity, and 20 percent were because abortion was rejected. This is very effective screening, and shows the usefulness of an effective carrier screening, prenatal screening, and counseling service in controlling an untreatable genetic disorder. Another successful screening program for thalassemia was performed in Cyprus, with the cooperation of the local church, so that all couples who were getting married were asked to provide certificates showing their alleles. This represents a good cooperation between geneticists and the church, who were effective agents for the procedure, to reduce the suffering that would otherwise have been caused.
The above case has worked for relatively small
countries, but people are now considering carrier testing of populations
for the common disease among Caucasians, cystic fibrosis (36).
If two carriers of the recessive gene for cystic fibrosis are
married, then they will have a one in four chance of a child who
will suffer from the disease. If they do not want to use selective
abortion but do not want to risk having such a child, then either
premarital or pregnancy screening could be used. In one study
pregnant women were tested first, and then carriers' husbands
were tested, to determine the risk of the disease in the fetus
before attempting fetal testing (37). In the four day period
waiting for the result of the carrier status of the husband there
was anxiety, which was relieved upon hearing a negative result.
It makes us consider whether it is better to perform this test
before pregnancy. The American Society of Human Genetics recommended
that general screening of the population should wait until all
major mutations are identified, and also until there is a better
idea of the education and counseling that could be given to carriers
of cystic fibrosis. Commercially performed tests are available
in the UK and the USA, and in the UK mail order testing is available.
Although there is pressure to use new information immediately,
there is a general need for a full range of prescreening and follow-up
services to be available for the population to be screened, before
a systematic program is introduced. Another ethical dilemma of
predictive certainty is highlighted by the large number of mutations
described, in which individual families may have particular mutations,
and their disease may not be detected by the general tests.
There are different stages at which fetuses can be screened for genetic disease or abnormalities, as discussed in previous chapters. As far as the ethics and the distress and the health risk to the mother are concerned, the earlier the screening is performed, the better. In addition to the timing issue is the risk to the mother or fetus of the invasive techniques, the principle of do no harm, and the accessibility or cost of the techniques arising from justice considerations. The techniques that can be offered include:
1) Chorionic villi sampling
4) Maternal blood serum sampling
6) Isolation of fetal cells in maternal blood
7) Embryo biopsy or preimplantation diagnosis
Invasive fetal sampling is labor intensive so that currently only a small proportion of the population can be screened even if it is considered desirable. Chorionic villi sampling (CVS) or amniocentesis are associated with a 1-2 percent risk of miscarriage after the sampling due to the procedure. Therefore, to minimize risk and maximize use of resources, samples are taken from those fetuses considered at high risk, i.e. those of older mothers or parents who have a history of genetic disease.
CVS has the advantage of being able to be performed earlier than amniocentesis, however it may have increased risk of fetal harm. This raises an ethical dilemma of whether a decision earlier in pregnancy is preferable to a increase in risk of miscarriage to the fetus, or possible limb defects. Who should decide which to use? In practice the experience of the local prenatal diagnosis service may well determine which is the best choice, as experience with a technique lowers the risks. Ideally non-directive counseling would include choice of technique, balancing the two procedures; however this situation is possible only when both options are available. The decision would then be made based on the preferences for pregnancy outcomes that the women have (38)
Fetoscopy involves examination of the fetus by percutaneous transabdominal uterine endoscopy and anatomical malformations can be directly visualized. It can be performed after 14 weeks, but has a 3-5 percent risk of miscarriage. In this method the fetus can be viewed through a hollow tube that is inserted into the amniotic sac. It may also be used for the removal of a sample of tissue from the fetus. The sampling of fetal blood by percutaneous umbilical blood sampling may also be performed. During this technique, an ultrasonographically guided needle is inserted into the umbilical blood vessel to withdraw a sample. The procedure can be performed on an outpatient basis, and does not require maternal sedation, and is safer than fetoscopy.
Ideally invasive techniques only follow non-invasive tests, so that a mixture of different methods may be combined, for instance the first screening may be maternal blood serum protein marker testing, and if certain proteins are detected, CVS or amniocentesis may be used to detect spina bifida, or Down's syndrome. The analysis of maternal blood for the level of alpha-fetoprotein, human chorionic gonadotropin and estriol, can lead to the detection of 60-70 percent of trisomy-21 (Down's syndrome) pregnancies. This is economically viable for mass screening, but further requirements are desirable, cost-effectiveness is one part of the ethical equation. Although in some countries serum screening is focused on women 35 years of age and older because of the higher frequency of chromosomal abnormalities, ethically we could argue that all women could be offered the option to enhance their choice (39). A positive result selects patients for the fetal screening. The statistical risk associations of serum screening require further counseling, but technically, serum screening allows total population screening. The problem is whether counseling resources match the ease of blood sampling. In California, all women have to sign a consent or refusal form for this voluntary testing, and can withdraw at any point from the program.
Ultrasound is the most widely used method of prenatal diagnosis and presents no proven risk to the fetus, although it is not recommended to be used excessively. The extent of use depends on the availability of the ultrasound machines. In Japan for example, it is often used for every monthly visit during prenatal care. There are ethical concerns that this visualization of the fetus affects the emotional relationship between the mother and the fetus, which in the case of fetal abnormality may make the decision for selective abortion more difficult. If that is the decision is still considered right by the mother after birth, then it has a benefit, however this may not always be the case. The use of ultrasound is very common in all industrialized countries and the sociological impact of this on mother-child relationships are not full understood.
Two other techniques that are expected to have greater impact in the future, as discussed in earlier chapters, are isolation of fetal cells from maternal blood, and preimplantation diagnosis. The practice of isolating fetal cells from maternal blood is advancing rapidly, and has been used for diseases such as sickle cell anemia and thalassemia (40). If the number of false positives found in these tests, which if non-checked could mean that an unaffected fetus is aborted, is reduced and the rate of false negatives is made very low, we can expect this to become mainstream and offered to all pregnant women.
Preimplantation screening on the other hand has the advantage of selection before implantation but must be associated with embryo transfer afterward, which requires a higher level of technical commitment and cost. Enough babies have been born to confirm its initial safety, and it is certainly less traumatic than abortion after prenatal diagnosis, at the earliest at 6-8 weeks after conception. However, it might never be widely provided, because it is limited to infertility clinics, and to parents who know that they carry a disease. It might be more ethically acceptable to use abortion, so the spirit of parental autonomy would support the provision of such services even when prenatal diagnosis is available, but it is unlikely that we could ethically justify the government funding of such tests unless they provide services for general in vitro fertilization and embryo transfer for infertile couples.
The problem with fetal screening coupled with selective abortion, as discussed below, is that we might not be able to eliminate the disease without eliminating the subject of the disease. We need to answer the question of the status of the embryo? If we take a gradualist view, then we would aim to do screening before the time that abortion is considered unethical. To be morally consistent if the embryo is considered to be of absolute protectable status at a certain time, then if at any period after those dates the living embryo is aborted the death of an embryo is unethical. To the absolutist, there are factors of the parents to be considered, but they should not be given priority after the embryo has protectable human status. When detection methods are available for screening at the earlier age then the approach of screening and selective abortion can be used ethically. The exception to this developmental limit might be if it were certain that the fetus was destined to die when born.
The range of time limits considered acceptable by most ethicists for selective abortion would generally be between the formation of the primitive streak and individualization at 14 days, and either the time of brain life, or viability, or birth (4). If a fetus has a serious genetic impairment, with a consequence of serious mental deficiency, some people might say that the fetus does not, and will not in the future, have a "life" as "normal" humans have a life. Its potentiality is different. Still many believe potential spiritual relationships are present in all human fetuses.
There is an increasing recognition that fetuses
should be regarded as the second patient. This will increase as
fetal surgery increases, a technique that was reviewed earlier
in this book. The fetus makes claims for a right to nutrition,
protection, and therapy (41). The quality of human beings, the
soul, our essence, unique individuality, with its associated dignity
or reverence means that human beings have a sanctity. However,
we should not contend, as some arguments against abortion do,
that existence is a good in itself because all other goods depend
on it. Some types of existence are not, and especially if there
is no person, then there is no spiritual existence. Abortion
is one of the key moral problems in this area, and in some countries
it has also become a major political issue also, however history
and the split opinion found in every country suggests that it
Treatment or Abortion, and What Diseases to Screen
A fundamental question, that will need to be addressed in each country, is "What genetic diseases can be screened for in prenatal diagnosis?" (42), and "What screening should be available under the public health care system?" A British study suggests that the disease and severity are more important criteria of acceptability for most patients than the time at which prenatal diagnosis and selective abortion are performed (43). Concerns of justice would call for offering services to as many people as possible. In developing countries services may concentrate only on the most prevalent diseases, for example in much of Africa, sickle cell disease is compelling, with 25 percent of the population of Nigeria carrying the recessive allele for this disease. In Middle Eastern countries, consanguineous marriages are still very common, and this may be the most urgent concern.
There are ethical problems concerning not only the prevalence but also the therapeutic or termination options that are available. The options are determined by the law, especially in countries in which termination of pregnancy for reasons of fetal handicap are limited in total or by time period, as discussed in the previous chapter. The options also depend on our capacity to treat the disease, for example, can we give them eyeglasses, or a hearing aid, or is it a disease with no treatment. As society changes people can construct a social need for the testing (44, 45) although upon reflection we may question whether it is really in the best interest of the persons or families and society. It may not be in the best interest to know all the genetic traits that we or a fetus possess, when they are not related to health conditions (46).
For people who consider abortion always to be unethical, there are still good reasons to use prenatal diagnosis. The procedure may be of significant benefit to both mother and child. Most results will show that the fetus is normal, and so the principle benefit of the test will be to alleviate worry regarding the fetus. This worry can be a significant psychological burden to some mothers and families. The decision regarding abortion should not be considered until after the test results. In the case of multiple test results, for example serum testing, even if an abnormal level of maternal serum AFP is found, it is usually not due to a neural tube defect, but because of other causes and it can alert the physician to other pregnancy complications. The detection of abnormalities by other tests can significantly alter the care of affected fetuses, and allow them to be born in hospitals where appropriate and immediately available neonatal care can positively influence long-term survival and health.
In some circumstances it is better to know that the fetus has a serious genetic abnormality so that if the fetus requires very intensive care and puts the mother at some risk, then the parents who reject abortion may still consider it best to let the fetus die, and to be content with letting nature take its course. If a fetus has a serious abnormality it may still be better to be aware of this before the child is born. The parents can chose to raise the child, and advance knowledge allows them to prepare educationally, emotionally, physically and financially for the care of the child. There is very little risk attached to prenatal screening and in view of the advantages to the parents and child to be, it should be widely used where available. Although we would never consider selective abortion as compulsory or as official government policy in a democratic country, the benefits of ultrasound or serum screening are sufficient in industrialized countries to make it standard policy, although because it involves the mother's body, her consent is required.
The results of genetic screening may pose a dilemma to the parents if the fetus is known to have a genetic defect that will cause disease after birth. They must consider whether induced abortion is a satisfactory "treatment". Opinions regarding whether death before birth is preferable to disability after birth vary greatly and they depend on the status given to the human embryo. There are several key questions. Can a barrier on the slippery slope between severe disease and hair colour be drawn? Should a rigid boundary limit be imposed if it can? In which diseases do we consider no life at all to be desirable to a life of much suffering?
Some parents of children who have a late onset genetic disease such as Huntington's disease, may want their children to be sterilized so that they will not pass on the harmful gene to the next generation, however that is clearly a question for the children to decide for themselves later in life. Presymptomatic testing has highlighted more of the ethical problems that arise in genetic screening than some "simpler" cases. In most screening services for late onset diseases, very careful selection of the test subjects is performed. The applicants for testing may come for counseling several times before the decision to test is made and the information is given. The results are always given in face-to-face meetings, not over the telephone. Post test counseling must also be sort, and a companion is often required to accompany the person awaiting the result. People who are emotionally unstable are not tested. This level of counseling is not possible for prenatal diagnosis, but certain persons may require it. Ethically the standards for counseling are not determined by any certain number of sessions, but rather by the way the person copes. Beneficence involves the protection of the patient from harm, which in this case may mean those who are emotionally unable to face the results of such a test.
An important question facing the counselor is whether it is ethical to use abortion for treatable conditions. An example of this is phenylketonuria (PKU), which when detected as a newborn, can be treated by dietary measures, with little ill effects, although there is suggestion that there is a higher probability of women with PKU giving birth to retarded children (47). The people still require special care. In practice most families that have a PKU child do not use prenatal screening on the next fetus, but attitudes may change.
Another complication is that the progress and severity of different diseases vary, so only some can be treated. There are also differences in expressivity, one person may express the disease to a different extent, or at a different age, to another. Sometimes this is due to multiple gene activity, or the presence of some environmental factors as is the case with Wilms Tumour, or Retinoblastoma, or Glucose-6-phosphate dehydrogenase deficiency. On the other side of the line might be short-sightedness which can be corrected with eyeglasses, because this condition poses very few problems in most societies. Similarly, we may be able to screen for the presence of a normal growth hormone gene, but because adequate therapy is available, it is like the PKU case if we perform prenatal diagnosis for this type of dwarfism. Polymorphism further complicates risk prediction.
People tend to be more concerned about genetic screening tests for people with mental diseases. An interesting, and sad, story of this type of screening was the case of men who have an extra Y chromosome, called the XYY syndrome. They were imprisoned for longer periods if they had this (48), because they were falsely believed to be violent. This screening lead to unfair labeling of people, such as the very weak connection with criminality believed to be associated with the XYY condition. This idea of geneticophobia has been a reason for social discrimination. Many still advocate continued genetic study to see the influence of genes on behaviour, it has important purposes but should be free of any harmful labeling.
Findings that there are associations between an allele of the gene for dopamine D2 receptor and alcoholism suggest that it may become technically possible to do genetic screening for a tendency for addictive behaviour. There has been two decades of research which have shown that part of the vulnerability to becoming alcoholic after exposure to alcohol is inherited (49). Alcoholism is a common serious disease and may not always be caused by genetic factors. However, many people may be at elevated risk for alcoholism, so we must consider whether we should screen for such alleles if there is some therapy available, or to know who to offer alcoholism prevention schemes to? Genetically diseases such as coronary heart disease and diabetes are complex also, and are influenced by diet and environment. How should our criteria of acceptable diseases for screening be influenced by the accepted social norms of a normal diet and lifestyle?
The types of criteria that are important for
parents to consider when reaching a decision include the severity
of the disorder and its effect on future life (including life
expectancy); the physical, emotional and economic impact on the
family; availability of medical management and special facilities
to care for the child to be; the reliability of diagnosis and
prognosis; effect on society, and the value placed on the human
embryo. These decisions will become complex, as the variety of
different genetic diseases of varying severity's are detectable.
For the counselor, should these judgments to offer or refuse screening
tests be determined by fixed rules or a list, or considered case
by case given the persons likely environment? If we allow case
by case then it is open to being dependent upon the arbitrary
choices of the service provider, and open to a free market selection.
Ethically we can ask whether we can prevent people's free choices,
and if we can it is certainly a difficult line for many diseases.
Reproductive Choice versus Genetic Freedom, and Fears of Eugenics
Even if the decisions to seek prenatal diagnosis remain voluntary, society can influence the decisions that individuals make. Society could say that it would not provide health care for some "avoidable" diseases, as that is inconsistent with public fairness to health resources. Society can publicize the diagnostic services much more, or offer incentives to accepting it. There is a fundamental question of how far to develop alternative therapies, which are often expensive. While some of the conditions that arise in accidents are similar and the technology could be transferred, limits may be placed. Ethically a person who has the bad luck to have a genetic disease or an accident, has an equal claim to treatment. It would be unethical for the government to refuse to contribute to the care of children who suffer from genetic disease because their parents refused to use genetic screening, because it is unjust to blame the children for their parents actions. If free choice is lost there will be a large cost in human dignity, which was the main lesson of the enforced eugenic programs of the 20th century in the United States or Nazi Germany.
The United Nations World Population plan of action declares that "All couples and individuals have a basic right to decide freely and responsibly the number and spacing of their children". There are several ideas in this statement, and we can find cases in which all aspects of the statement have, and may still be, prevented. Many are conditional and are prevented in some societies. A question must be, "Which aspects of reproductive freedom can be limited without violating the basic idea of autonomy?"
The right to rear children is conditional on the ability of the parents to look after the children, and not to abuse them. The number of children is limited by very strong policy in some countries, such as in China, because of overpopulation. Different societies have used different criteria to control access to infertility treatments. The idea of the right to marry anyone, but has been prevented in some countries, or by premarital testing laws, or making a class of non-marriable individuals, and is subject to family restrictions.
Reproductive freedom is based on the need for bodily-self-determination, or integrity. It is not based on any "right to procreate" but on the freedom to determine when, whether and under what conditions we can bear children. A second claim for reproductive freedom for women is because it is predominantly women who must bear the major consequences of pregnancy and raising the child. The interests of the child are a valid part of the argument, even though the person may not yet exist.
Some claim that the major thrust of the eugenics movement today is in fetal screening and selective abortion (50). The language has moved to fetal "rights to health and well-being. The selection criteria has moved from the emphasis on behaviour, to emphasis on health being the major concern. This argument is based on the traditional theme that we should not burden society and successive generations with genetic diseases, as discussed last chapter. Joseph Fletcher (51) discussed various types of child abuse, including individuals who preconceptively or prenatally abuse children by "knowingly passing on or risking passing on genetic disease". He argued that argued that reproduction that is planned and controlled is more human than playing "genetic roulette". Humans are distinguished from animals because they have the ability to chose traits. We have seen the emergence of court cases such as wrongful life, in which the fetus is meant to have a "right to health" (52). However, because the fetus is attached to the mother the choices about treatment should only be made with her informed consent (53), as recommended by the US President's Commission (54), which stressed the autonomy of individuals meant that only under the special circumstances when people are unable to protect themselves, could screening be compulsory. The other arguments, such as social utility (economics), allocation of resources evenly, and improving society's "genetic health" are not sufficient to make genetic screening be enforced. This position has been accepted in case law in European and North American traditions also.
We can define genetic freedom as the freedom to bring about the conception of a child with any characters, whether they are good or bad, desired or undesired (4). A fundamental principle of bioethics is autonomy, the freedom of individuals to make decisions regarding their own lives. It is not unconditional freedom, because part of the concept of autonomy must be a recognition of other people's autonomy, or values. Freedom is limited by recognition of other's autonomy to pursue to an equal degree of freedom. There are limits in the way that we should affect other people. The idea of limiting genetic freedom also involves how we treat other people, but people who may not yet exist. There are a few examples of how we already accept limits on behaviour of individuals because of the affect on future generations. Pregnant women may be prohibited from certain areas of risk in factories. Foods and drugs are carefully screened to avoid any agents that may cause birth defects.
Compelled medical treatment of pregnant women
is generally not ethical and it is not legal. Prenatal diagnosis
cannot be imposed by law, or by any other person, it relies on
the informed consent of the mother (55). This is important to
maintain as population screening efforts may extend coverage
to all (56). Society may gain more by allowing each pregnant woman
to live as she deems acceptable rather than by compelling certain
screening or fetal therapy (57). Voluntary measures are better
to protect the body, which are different than decisions made directly
because of desired characters in the fetus. There are two types
of cases. One type is when there is some therapy for the affliction
that should be started before birth. In this case, there are
some grounds for enforcing some types of treatment, such as blood
transfusions. Women have been put in prison to prevent them from
taking drugs during pregnancy. There is much legal debate in the
USA. The second case occurs when there is no therapy, and the
preferred course by the family's medical insurance company is
selective abortion. Courts remain unwilling to condone abortion
and this will not occur in societies that recognize the autonomy
of mothers or some right to life of a fetus. If there is no therapy
then society cannot ethically enforce abortion, even though it
can control the application of medical resources in a national
Although sex is not a disease anymore than life itself is, but a phenotype, it continues to be a reason used in practice for prenatal diagnosis and selective abortion. Can society allow individuals to have free choice over the use of diagnosis when there is no medical reason for it? Sex selection can be for two reasons, excluding sex-linked genetic disease. One reason is when a family has a preference for one sex, perhaps as a result of already having other children of another sex. The other reason is for social or cultural reasons which could be a result of inequality, for example in many countries of the world, feminicide is practiced.
Sex selection is a precedent for genetic screening for characters that have nothing to do with disease so it is interesting to ask what attitudes genetic counselors and the public have toward it. It is a dangerous precedent to allow sex selection to be part of reproductive choice. The attitudes of doctors to allowing sex selective abortions vary between different countries. In certain cases the physicians in countries such as the USA would comply with requests for prenatal sex selection (58). In a case in which a couple with four healthy daughters wants a son, and will abort the fetus if it is female or if there is no determination, many would comply with this request. In a 1985 survey, the percentages of genetic counselors who would comply in various countries were as follows: USA 62 percent, Hungary 60 percent, Canada 47 percent, Sweden 38 percent, Israel 33 percent, Brazil 30 percent, Greece 29 percent, United Kingdom 24 percent. Most counselors argued that they would comply out of respect for the patient's autonomy and rights of choice, only in Hungary did they add the threat of abortion as being significant. The trend over time is to be more tolerant of sex selection, perhaps extending the other trends of control over pregnancy and birth of children.
Arguments against sex selection include the fact that being a particular sex is not a disease, that if sex selection were used it could lead to social inequality between the sexes, that sex selection is not a sufficient reason for abortion, and that sex selection is a waste of resources because there are many genuine cases to deal with. The two major arguments for sex selection are individual liberty, and that that sex selection may reduce population growth in countries I which people continue having children until they have a male child. When having smaller families there is greater pressure for sex selection, but it should still be resisted. There is no evidence to support the claims that sex selection would enhance the quality of life of child and family (59). Even if prenatal diagnosis became common for all, it would still be objectionable because it undermines the major moral reason that justifies prenatal diagnosis and selective abortion - the prevention of serious genetic disease (58).
Sex is one character that is not related to disease, as are others such as height, eye and hair colour, and skin colour. Many parents include some of these characters when they think of their ideal child. Sex selection would set a precedent for the near future, as the number of testable characters increases. It is important to take a stand now against this growing trend. It may be better to avoid making many reproductive laws, but it may still be necessary if genetic counseling and information cannot control the abuse of selective abortion. A simple method is to withhold the information of fetal sex, which is already done in some clinics. It is a case in which directive counseling, and possibly legal control are required.
In the current situation we could use the argument that genetic screening should not be performed for non-disease conditions because there is already a shortage of resources. In some countries, money can buy anything, including many unnecessary medical resources, we can also say that this is wrong in a world, or even country, in which many people do not get adequate medical resources. However individuals favoring free market rights to health care purchasing would dismiss this argument. It also begs the underlying question, if resources were available would it be ethical? We can make the situation easier if we consider that there is no risk involved or abortion required in the process, but there is preconception control.
One view is that there is no difference between altering genes, and the variability in the environment to which parents can subject their children. However, we can argue that the danger in this is limiting something we could call the "natural autonomy of the new individuals". This would introduce the concept of a "natural genetic autonomy", the freedom to let the genes come together naturally and to let that individual develop their genetic potential without unnecessary interference by parents or society (4). Although we may give freedom to nurture children in various ways, there are imposed limits.
The basic justifications that are used to limit reproductive choice are paternalism, the public health, and economics. Paternalism is the protection of others against the effects of their own "wrong" decisions; however, that should not enforce behaviour of people who are able to make a balanced decision. We should be responsible for our own behaviour, but we cannot enforce others to follow our own values. The exceptions may be individuals who are mentally incompetent. The public health and economic arguments are much less justifiable reasons, especially in the world in which so much government money is spend on military spending. Society has little moral weight to enforce behaviour change on others, until they have eliminated many factors that damage health and misuse money. The matter of limiting parental choice may be best left to the moral values of individual physicians than limiting offered services (60)
There is another argument that if we let society or parents chose characters in their children thiswill have a harmful effect on social attitudes to people who fail to meet those characters. A problem with the increasing availability of genetic screening is that although it can help people have children free of known genetic defects, it makes life more difficult for many parents who did not use screening and their children who suffer from the disease. It may increasingly be seen as not an act of fate but as the parents' fault . Modern society is moving towards viewing reproduction as a commodity, producing a luxury item, a newborn child free of defect. This may make people less tolerant of the variety of human beings. In the case of sex selection it represents prejudicial attitudes which are inappropriate in a world where we are trying to get rid of such prejudice. There is also the argument of reducing genetic variability, but it is doubtful whether this sort of selection would really have much affect biologically. The major affect is on reduced social variability.
Even within the family there are concerns, that parental concern with choosing characters of children is incompatible with the unconditional acceptance that is essential to good parenting. The more a child's genome is subject to manipulation, and is a result of the choices of others, the more we can consider children to be a social products and no longer unique persons. Society must promote good attitudes toward children and the family.
The President's Commission (54) and others
have recommended that public policy should discourage sex selection
but that it should not be a legal prohibition. One of the major
reasons given was that it would be impractical. However, a legal
prohibition may be quite possible, by withholding information
regarding the sex of the fetus during genetic counseling. Wertz
and Fletcher (58) argue against a legal prohibition, unless attitudes
in a particular country make it the only means to prevent it.
In India where it is against the law, sex selection is still
practiced, making the gap between reality and law greater, which
may not always have good social effects. National and international
medical organizations should at least make strong stands that
their members should follow.
Privacy of Genetic Information and Tissue Storage
After prenatal diagnosis and counseling are considered, the question of medical records, and storage of blood, DNA, cells, tissue and information is raised. Many individuals will be identified who carry a gene for a genetic disease, and we have seen a dramatic increase in the amount of patient genetic data that can be collected. This raises many questions regarding the rights of individual privacy and familial privacy, and what information others can have access to (61). The type of information that can be screened for covers predisposition to diseases, and may reveal important hints about a person's physical or intellectual potential.
The data are obtained because they can play an important role in the life of the individual, affecting the choice of spouse, psychological health, reproductive decisions such as whether to have children using own gametes, and whether to use prenatal screening and selective abortion or therapy. In addition to the direct purpose of reproductive planning, some findings may relate to decisions regarding personal health risks that may be affected by diet, smoking, etc., and the individual's type of work. Knowledge may affect insurance schemes, employment and retirement, as discussed elsewhere (62, 63). The genetic information can be of great benefit to the individual person to know about their genetic constitution.
Closely related individuals may share the disorder, so if one member of the family is tested the others may follow that lead. Respect for confidentiality is one of the key principles in the development of genetic screening programs. Genetic diagnostic information must be held strictly confidential. It is considered essential to maintaining a good doctor-patient relationship. If the patient does not trust the doctor, then he or she may not reveal delicate health issues to the doctor. The only exception is when another family member needs to know the information because of a direct medical risk that would be averted if the information is known. If a person is found to be positive, will relatives be warned of their risk? Is there a right to know, and a right not to know? If genetic registrars are established, should relatives be involved in deciding whether family member's data should be recorded, because the information could be used to affect other family members as well as that individual?
It may be very difficult to protect individual that do not want to learn "bad" news from their relative's test results. However it may be done, it is one thing to maintain privacy, and another to always tell the truth. A similar dilemma often arises in the case of non-paternity, the genetic father is not the husband of the woman. A limited amount of paternalism, in the sense of considering the adverse consequences of revealing the information, may be justified.
In certain cases there may be a duty to know genetic information if a third party might be harmed. If children are born, then this could save them from a disease. What happens as new genetic diseases are able to be screened. Should the samples taken be used for a new test when evidence suggests that the person may be at risk for that disease. Consent to use tissue for one test does not mean consent for other tests, unless it has been specifically stated (64). Recently some forms include options for consent to additional tests at the judgment of the physician, but most do not. The physician may at least have a duty to inform the family of the availability of the new test, although legally, we would not usually expect this to be formalized.
There are different DNA banks that have been created in many genetic clinics. There are guidelines that detail some of the precautions that should be made in gathering samples from persons for genetics research (65). The purpose of DNA banks is to provide for the future requirements of those families that gave the samples. One criteria for the release of samples or information is that non-identifying information could be released considering the prospects of general benefit, but identifying information should only be given with the consent of the donor (61).
There have been some publications that have deliberately changed family pedigrees to prevent relatives from finding out information regarding their status, such as whether they have Huntington's disease alleles. Although this is good to protect people's right to know, and right not to know, it must be very clearly noted in any paper that this has been done. Otherwise, people may not be able to do future research, for some association with sex or age for instance, that may be useful in elucidating the disease. The original data should be stored in some repository so that researchers can apply for it. For example, a Venezuelan Huntington's disease family pedigree collected by international researchers involves more than 8,000 individuals, which is a very important resource for other genetic researchers, now and in the future in the study of other genes. There is a balance that can be maintained to ensure both privacy, and scientific integrity. There is also the question of where actual samples of DNA should be held.
DNA fingerprinting, using restriction enzyme
patterns to compare similarity of band patterns between two samples,
can also be used for prenatal diagnosis. Approximately half of
each DNA fingerprint is inherited from each parent. Comparison
of the parent's and child's DNA fingerprints can reveal the real
genetic relationships. The evidence is accepted in many countries
for criminal cases, and also in disputed paternity cases for immigration
purposes. It has been used to identify whether a fetus is genetically
related to the partner or rapist of a woman, raising further questions
of privacy. The dilemma of a woman who becomes pregnant after
rape is doubt regarding the fetal origins, and prenatal diagnosis
can resolve the dilemma and save the life of the fetus if it comes
from the partner. Whether a woman could choose among different
partners would be more difficult.
Ethics and reliability
Diagnosis implies that we can accurately predict a disease, to be certain to tell a parent who may make a life or death decision about the future of their fetus. The DNA probes and genetic information is perceived to be 100 percent reliable by many people. The public must to be educated against this type of blind faith in genetic techniques, that was seen 70 years ago. That is a lesson about the eugenics programs of history. The uncertainty of prognosis requires special stressing in multifactorial disorders, and psychiatric diseases.
There is much commercial interest in screening,
because the market is very large. Companies are working on many
diseases, and packages that can screen a 100 or more disorders
should eventuate in the near future. There is a major ethical
problem in the delivery of services. There is unfairness in access
to genetic services, and services are insufficient to meet needs.
This is especially acute for individuals, families and pregnant
women who are not referred to genetic services by physicians,
who suffer from poverty, and lack of education, or who live far
from a genetic centre. Beyond this is the issue of the accuracy
of genetic tests and the conveying of results to patients directly
from general practice physicians who may not understand the problems
of the tests (66). Companies pushing profit margins may compromise
accuracy and safety unless general standards are enforced. There
is a shortage of trained personal for genetic counseling, and
this will exist for some time, as the new clinics are established.
Testing needs to be done only in clinics with good support for
counseling, but counseling also costs money. In a competitive
free market costs will be reduced, as it will if it cannot be
included in health insurance reimbursement points schemes. There
are problems also in extending academic services to cover population
needs (67), this question is still unresolved.
Public acceptance of prenatal diagnosis
Ultimately the client and counselor are individuals existing in a social milieu, which may impose restrictions on the extent of their interactions and freedom, as discussed above. Therefore public opinion, and the attitudes of persons involved in the policy making are quite important to the common "ethics" of the techniques. There are two broad approaches to study user attitudes to genetic screening: one is uptake of the screening in practice, and the other is attitudes to a hypothetical situation. The use depends on the access to the screening and the prior information to know that screening exists. Measuring use, and especially studies to look at the attitudes that persons with close knowledge of a disease have toward screening, is a valuable approach; however, general public attitudes are also interesting. Moreover, in many countries genetic screening is still not common, so only such general surveys using hypothetical questions are available.
Another important point in policy for regulating genetic screening is to whom should we look - the specialists or the public. An international survey of genetic counselors has been reported (13), which explored the extent to which non-directive counseling is used, and some factors clinicians use. If we are to pursue non-directive genetic counseling, and the practice of informed choice of medical options by the public, the question faced is "Can the public decide?" How do ordinary people, or non-geneticists, reach decisions, and how informed are they? Opinion surveys are prone to bias and numbers may be misused only to provide a scientific aura to reinforce preexisting views. We need to develop approaches to examine the reasoning that people have, which may allow us to better predict the social impact of genetics. The International Bioethics Survey of public and/or university students, including open questions on how people think about life, disease, and genetics was performed in 1993 in Australia, Hong Kong, India, Israel, Japan, New Zealand, The Philippines, Russia, Singapore and Thailand (1).
People in all countries surveyed were very positive about sharing disease information with a spouse, and family, but not with employers and insurers. When the question was first used in the USA (68), there was little weight given to the privacy arguments in the question of insurer or employer access to genetic data, despite the importance given to this by ethicists. In questions about privacy of sharing genetic information, there was less significant agreement to share information with the family than with a spouse, except in Japan, where sharing with the family was rated equally important. The difference in the family result may represent attitudes to family involvement in disease and how much disease is seen as a family problem. In addition to the Japanese public and students, approximately 90 percent of the students from Thailand, Philippines and Singapore also thought the family deserved to know, which was significantly different to the Australasian and Indian public and students and Hong Kong students. A family in all countries may support a sick person, but it is interesting to see whether the individual or family is seen as the basic unit of autonomy when it comes to private medical information. The support for family knowledge of genetic disease has some relevance to genetic counseling, and supports some family involvement. These results suggest that family-centred counseling may be more appropriate in Japan and Thailand than in the other countries.
In all samples the most common feeling expressed towards people who had hemophilia, muscular dystrophy, schizophrenia, depression, neurosis and AIDS, was sympathy (1). Between 61-92 percent of individuals approved of making prenatal genetic screening available under government funded medicine. It was similar to the support for making it available under the guidance of a physician in the USA (68, 69). Between 53-84 percent said that they would personally use genetic screening, whereas 6-32 percent said that they would not (1). Approximately one-fifth of the individuals said that the testing would help the family or parents, and other reasons included a desire to know, the quality of life of the child-to-be, and saving the life of the fetus. One-tenth to one-fifth of individuals said that they would not use prenatal tests, as seen in several US surveys (68, 69, 70). Only 1-2 percent of Japanese individuals said that the fetus had a right to life; compared with 3-4 percent in Australia and 4-8 percent in NZ. There was surprisingly little objection on religious terms in Thailand, considering the Thai Buddhist views on the sanctity of life.
Very few fears of eugenics were expressed anywhere. Eugenics is the belief that good genes (i.e. genes that don't cause disease) are better to leave to children than disease-causing genes. Approximately 10 percent of the respondents of the survey from Russia, and many from India also, gave direct eugenic reasons for support of genetic screening (1), significantly more than in the other countries. However, if we combine this type of reason with economic reasons, we find that Australia, New Zealand and Thailand also show this type of eugenic support. Japanese individuals showed the least support for this type of thinking. In this survey eugenic ideas found both positive support (genetic screening), and negative reaction (gene therapy for enhancement) (71). The questions regarding genetic screening and gene therapy suggest positive support for eugenics among a significant portion of the population, especially in India and Thailand, and from other surveys in China. Whether eugenic views of improved genes and health for individuals, a positive view in itself, can be separated from the negative eugenic social forces of conformity, and discrimination against people with disease, is a question only time will truly answer.
Ultimately public opinion is expressed in laws, as reviewed in the previous chapter of this book. The Council of Europe Bioethics Convention of 1996 is the largest attempt to date to specifically regulate bioethical issues, involving the 35 countries of Europe, and one article limits genetic screening or predictive testing to medical reasons.
In a related bioethics high school education survey in Australia, Japan and New Zealand, 74 percent, 40 percent, and 67 percent of biology teachers, and 29 percent, 19 percent, and 29 percent of social teachers, respectively, had discussed the ethical or social issues associated with prenatal diagnosis in class (72). In Belgium a study found that education of human genetics was not only a prerequisite for informed decision making but also for avoiding negative psychological effects of the test (73). The issues of genetics and bioethics are welcomed by students (74). Education is a central issue to the genetic age. The surveys of the public (1) suggest that many people do have the ability to balance benefits and risks of genetic technology. This is necessary for bioethics, and balancing good and harm and is some indicator of the "bioethical maturity" of a society (75).
The attitudes within a country change over time, depending upon the influence of the media and public understanding. Two surveys conducted by the Prime Minister's Office in Japan asked whether it was good for people in general to use prenatal diagnosis, and in 1985, 64 percent said yes, 25 percent said no, and 12 percent didn't know; in 1990, 70 percent said yes, 17 percent said no, and 13 percent didn't know (76). The results of surveys conducted by Macer since 1991 (76, 77) suggest that approximately 70 percent of individuals are in favor of prenatal diagnosis being available under national health insurance, although it is not. Surveys from the Prime Minister's Office also asked people whether they thought it was good for couples to know the sex of the fetus before birth (not for sex selection, but just for knowledge), the responses in 1985 and 1990 were similar, with 35-36 percent answering yes, and 52-54 percent answering no. There was much clearer acceptance of prenatal diagnosis for the purpose of disease, the first question, than for merely knowledge of fetal sex. Similarly, the US public also reject the use of prenatal testing for fetal sex determination (78), except in the case that a couple already has three offspring of the same sex (70). In a telephone survey two thirds of respondents said they wanted to personally use prenatal genetic screening.
In the USA, willingness to use prenatal diagnosis
and attitudes toward abortion if a fetus is found to be suffering
from a serious disease appear to be distinct (70). The fetal
age and severity of disease are very important determinants (78).
In the USA, even people belonging to conservative religious groups
support the use of genetic testing (79), but there may be a higher
proportion of people who "don't know". Families whose
members suffer from cystic fibrosis seem less willing to personally
use selective abortion (78, 79), although they support the right
of others to use prenatal diagnosis and selective abortion (80,
81). A similar result is reported for sickle cell anemia prenatal
diagnosis in Nigeria (82). However, in Japan a survey of members
of the muscular dystrophy association found higher support for
personal use of prenatal diagnosis (patients 60 percent, and families
71 percent) than the general public (83).
Within nations there can be differences between
groups within society in the uptake of testing. In the USA there
is higher use of prenatal diagnosis by whites and Asians and less
use by African Americans and Hispanics (84). The uptake is also
influenced by the attitudes of physicians. In a study in Quebec
and France, more than half of the physicians surveyed would accept
selective abortion of a fetus with trisomy 21, however, Anglophone
doctors were somewhat more willing (85). In 1991 (76) and 1995
(77), I have conducted surveys of different population groups
inside Japan, on the approval for fetal diagnosis and gene therapy,
and the reasons given for the decision about fetal diagnosis.
The acceptance of gene therapy generally increased since 1991,
whereas the approval of fetal diagnosis stayed similar. The least
supportive groups surveyed were in 1995 the members of the Japan
Association of Bioethics, and the 1995 Doctors sample was of university
physicians. They were least supportive of fetal diagnosis; fewer
respondents gave a reason of "to save life", or "parent's
convenience", but more respondents gave reasons such as "to
improve genes" or "economy" (support for eugenics),
and "fetus has a right to life", "unnatural or
Playing God", "health risk", and "eugenic"
concerns. This result suggests that these persons with specialised
knowledge have more concrete ways of discussing the issue, perhaps
as a result of experience or debate. There also can be differences
between medical specialty (86).
There is universal ethical consensus that prenatal diagnosis should be available to families who seek it. The decision to use predictive genetic screening depends on the image of disease held by the person and society. There is clear public support in all countries in which surveys have been conducted for prenatal diagnosis, and also that it also should be available under national health insurance.
There is agreement that we need to avoid abuses of such screening, for non-disease conditions, such as sex selection, and for eugenic purposes, but the method to effect this is under dispute. Should this be by regulations, and should these regulations be international? A majority opinion would be that prenatal diagnosis of the fetus should only be performed for serious diseases. These include diseases that would result in serious mental or physical health damage to the fetus. In most cases the fetus is found not to be afflicted, so the test removes much anxiety from the parent's minds. Without the use of such tests to confirm the absence of disease, some mothers would have an abortion. In the case that the fetus is found to be afflicted from a disease there are two different possible courses of action. If there is a therapy available and treatment before birth is necessary to avoid health damage, the fetus can be treated for the detected disease. There have been increasing numbers of operations performed on fetuses in the womb (in utero), which have avoided permanent health damage to the fetus. Sometimes the fetus is removed from the womb, operated on, and then replaced to complete normal gestation. If the detected disease is untreatable, and is serious, then the option of selective abortion is available.
If we draw up regulations and guidelines, can different standards can be justified in different countries. The survey data generally finds that the total diversity in all samples is found in any one country or group. In every society there are people who want to use new genetic techniques such as prenatal genetic screening, and there are some who reject the concept of selective abortion. We should build a society which respects this division of opinion, and offers improved services to those who want to use them - while also providing counseling to help people reach decisions.
The call for international approaches (including education and guidelines) is based on several arguments, including shared biological heritage and destiny of human beings in all "nations", and the transitory nature of "nations" and the precedents for international law to protect common interests of humanity. Those calling for national guidelines argue that each culture should make their own standards because of national autonomy and because people in each country have different attitudes. Perhaps the key balancing issue is how divergent the perceptions and bioethical reasoning of peoples around the world are. This question can be partially addressed by a survey, and the result is pertinent to studies of social acceptance of medical technology, and perceptions of disease.
The clearest consensus is that the advances from the human genome project, and techniques that allow low cost multiple mutation screening, will flood the clinics with new possibilities. There has been some discussion of the ethical, social and legal impact issues of the human genome project in different countries (87, 88, 89), but the answers to the finer ethical questions remain mixed. The clinician may be able to provide more evidence to reach the answers in the future by continued systematic evaluation and reporting of the outcomes of prenatal diagnosis, so that the answers are not based only on speculation but on experience. With the essential maintenance of privacy, there is a need to monitor the combined effect of the individual choices that prenatal diagnosis offers our global society, so that we may really become more informed consumers and providers.
Please send comments to Email < Macer@sakura.cc.tsukuba.ac.jp >.