Autonomy

It is the patient who should be empowered and in charge when it comes to decisions that have to be made. The degree to which this is possible is a function of the quality of information given. Sometimes patients are still seeking some form of guidance to give them confidence in the decision they reach, and it will require the judgment of the clinician/counselor as to how much guidance is appropriate in a given situation. The patient should feel comfortable to proceed no further, and opt out freely at any stage of the process; this applies particularly in the context of predictive genetic testing.

Informed Choice

The patient is entitled to full information about all options available in a given situation, including the option of not participating. Potential consequences of each decision option should be discussed. No duress should be applied and the clinician/counselor should not have a vested interest in the patient pursuing any particular course of action.

Informed Consent

A patient is entitled to an honest and full explanation before any procedure or test is undertaken. Information should include details of the risks, limitations, implications, and possible outcomes of each procedure. In the current climate, with respect to full information and the doctor-patient contract, some form of signed consent is increasingly being obtained for every action that exposes the patient—access to medical records, clinical photography, genetic testing, and storage of DNA. In fact, there is no legal requirement to obtain signed consent for taking a blood test from which DNA is extracted and stored. The issue was addressed by the UK Human Tissue Act 2004. According to the act, DNA does not constitute ‘human tissue’ in the same way as biopsy samples or cellular material, for which formal consent is required, whether the tissue is from the living or the dead. The act does require that consent is formally obtained where cellular material is used to obtain genetic information for another person. In a clinical setting, this must be clearly discussed and documented.

In clinical genetics, many patients who are candidates for clinical examination and genetic testing are children or individuals with learning difficulties who may lack capacity to grant informed consent. Furthermore, the result of any examination or test may have only a small chance of directly benefiting the patient but is potentially very important for family members. Here the law is important. In England and Wales, the Mental Capacity Act of 2005 came into effect in 2007 and applies to adults aged 16 and older. It replaced case law for health (and social) care and there is a legal duty to use the legislation and apply the ‘Test for Capacity’ (Box 24.4) for any relevant decision for people who lack capacity. Decisions must take into account the ‘best interests’ of the patient, but can also embrace the wider interests that relate to the family. In England and Wales, the law allows for an appropriate person appointed by the Court of Protection to act on their behalf, whereas in Scotland it is legally permitted for certain designated adults, including family members, to give consent (or refuse) on behalf of a person lacking capacity.

Confidentiality

A patient has a right to complete confidentiality, and there are clearly many issues relating to genetic disease that a patient, or a couple, would wish to keep totally private. Stigmatization and guilt may still accompany the concept of hereditary illness. Traditionally, confidentiality should be breached only under extreme circumstances; for example, when it is deemed that an individual’s behavior could convey a high risk of harm to self or to others. In trying to help some patients in the genetics clinic, however, it may be desirable to have a sample of DNA from a key family member, necessitating at least some disclosure of detail. There is also the difficult area of sharing information and results between different regional genetic services. This is a complex and much debated area in the context of genetic and hereditary disease but the principle of patient consent for release and/or sharing of information should be the norm.

Universality

Much of traditional medical ethical thinking has upheld the autonomy of the individual as paramount. Growing appreciation of the ethical challenges posed by genetics has led to calls for a new pragmatism in bioethics, built on the concept that the human genome is fundamentally common to all humankind, and can—and indeed should—be considered a shared resource because we have a shared identity at this level. What we learn from one individual’s genome, from a family’s genome, or a population’s genome, carries potential benefits far beyond the immediate relevance and impact for that individual or family. From this it is a direct and natural step to consider how best the genetic information is exchanged, for the medical benefits may be far reaching. This ethical attitude therefore leads on to a realization of mutual respect, reciprocity, and world citizenry in the context of human genetics. It prompts the individual to consider his or her responsibility toward others, as well as to society, both in the present and in the future.

Meanwhile, however, very real ethical problems have to be faced and dealt with in some way, and it is to a few of these that we now turn.

Prenatal Diagnosis

Many methods are now widely available for diagnosing structural abnormalities and genetic disorders during the first and second trimesters (see Chapter 21). The past 35 to 40 years have seen the first real availability of choice in the context of pregnancy in human history. Not surprisingly, the issue of prenatal diagnosis and subsequent offer of termination of pregnancy raises many difficult issues for individuals and families, and raises serious questions about the way in which society views and cares for both children and adults with disability. In the United Kingdom, termination of pregnancy is permitted up to and beyond 24 weeks’ gestation if the fetus has a lethal condition such as anencephaly, or if there is a serious risk of major physical or mental handicap. For good reason, terms such as ‘serious’ are not defined in the relevant legislation, but this can inevitably lead to controversy over interpretation.

The difficulties surrounding prenatal diagnosis can be illustrated by considering some of the general principles that have already been discussed. At the top of the list comes informed consent. In the United Kingdom, approximately 70% of all pregnancies are monitored for the presence of a neural tube defect by measurement of α-fetoprotein in maternal serum at approximately 16 weeks’ gestation (p. 328). In theory, all women undergoing this test should have a full understanding of its potential implications. This also applies to every woman who is offered a detailed ultrasonographic scan to assess fetal anatomy at around 18 to 20 weeks’ gestation (p. 326). For fully informed consent to be obtained in these situations, it is essential that pregnant women should have access to detailed counseling by unhurried staff members who are knowledgeable, experienced, and sympathetic. In practice this may not always be so; indeed, there is evidence that the quality of information provided varies widely.

The most difficult problems in prenatal diagnosis are those involving autonomy and individual choice. This relates particularly to disease severity and who should make the decision that termination is justified. This can be illustrated by considering the following situations. In the first situation, parents whose first child, a boy, has autism are expecting another baby. They have read that autism is more common in boys than girls, so they request sexing of the fetus with a view to terminating a male fetus but continuing if the sex is female. Overall, however, the risk of having another child with autism is only about 5%. Such a request presents the clinician and counselor with a challenge. There is general agreement that sex selection for purely social reasons is not justified as grounds for termination of pregnancy, nor indeed for embryo selection by preimplantation genetic diagnosis (PGD), although in the United States, it is permissible to perform sex selection by PGD for ‘family balancing’. In the United Kingdom, the general public, through a public consultation process overseen by the Human Fertilization and Embryology Authority (HFEA), has overwhelmingly expressed the view that sex selection for social reasons and family balancing is not acceptable: children should be considered as gifts, not consumer commodities. But what about this situation, when the risk of a second child having autism is low and it cannot be guaranteed that a daughter would not be affected?

Next, consider the unusual but not unprecedented dilemma that arises when parents with an inherited condition indicate that they wish to continue with a pregnancy only if tests show that their unborn baby is also affected. Examples of conditions that could generate a request of this nature include achondroplasia and congenital sensorineural hearing loss. If the family’s autonomy and right to choose is to be respected, then their request should be granted. Many readers of this chapter will be uncomfortable with the suggestion that an unaffected pregnancy should be terminated. This particular scenario illustrates the difficulty of interpretation and defining what is normal.

The issue of autonomy and individual choice can also arise when a fetus is found to have a relatively mild abnormality, such as a non-syndromal cleft lip and palate, for which surgical correction usually achieves an excellent outcome. For some parents, particularly those who themselves have had an unhappy childhood because of being stigmatized for a similar problem, the prospect of having a similarly affected child can be unacceptable. Understandably, medical and nursing staff may feel very uneasy about complying with a request for termination of pregnancy in such situations.

It is inevitable that a subject as emotive as termination of pregnancy will generate controversy, and the ethical dilemmas that arise are not easily resolved. Proponents of choice argue that selective termination should be available, particularly if the alternative involves a lifetime of pain and suffering. More often than not, prenatal diagnostic techniques provide reassurance, and the fact that tests are available provides many couples with the necessary confidence to embark on a pregnancy. Without the option of prenatal tests, these couples might decide against trying to have further children. When viewed in the context of abortion in general, termination on the grounds of fetal abnormality constitutes less than 2% of the total of approximately 200,000 abortions carried out each year in the United Kingdom.

Those who hold opposing views argue on religious, moral or ethical grounds that selective termination is little less than legalized infanticide. Key to the ethical issue here are views on the status and rights of the embryo and fetus. For those who believe that the fertilized egg constitutes full human status, PGD and embryo research are unacceptable. Indeed, logically, for people who hold this belief all in-vitro fertilization (IVF) programs are unacceptable by virtue of generating thousands of spare human embryos to be kept in freezers, most never used. There is also concern that prenatal diagnostic screening programs could lead to a devaluing of the ‘disabled’ and ‘abnormal’ in society (notwithstanding that these terms are difficult to define and all too often used pejoratively), with a possible shift of resources away from their care to the funding of programs aimed at ‘preventing’ their birth. The debate about the ethics of prenatal diagnosis is a fierce one that will become even more difficult when genes are identified for common multifactorial disorders such as depression and schizophrenia. Mutations or polymorphisms in such genes are likely to confer a risk that the fetus will develop the condition as an adult, not that the individual will definitely be affected. The arrival of microarray-CGH technology, and in the future rapid automated genome sequencing, is raising the specter of wide-ranging, affordable antenatal genetic screening, well before we know how to identify all copy number polymorphisms and variants of unknown significance.

The results of public consultation exercises conducted by the Advisory Committee on Genetic Testing (subsumed into the Human Genetics Commission which was abolished in 2010) and the HFEA are reasonably reassuring. The views expressed support the applications of genetics in prenatal testing for serious disorders but concern over wider applications of the techniques. Similarly, research published by the British Social Attitudes survey, in the context of genetics research and gene manipulation for the detection of disease, suggested that the public supports these activities in general but expressed deep reservations for application of the technologies for genetic enhancement. Genetic enhancement, through manipulation of embryos or gametes, strikes at the very heart of what it means to have one’s own identity through natural laws of chance. This, it seems, is a powerful undercurrent in the understanding of who we are as individuals and as a species.

Predictive Testing In Childhood

Understandably, parents sometimes wish to know whether or not a child has inherited the gene for an adult-onset autosomal dominant disorder that runs in the family. It could be argued that this knowledge will help the parents guide their child toward the most appropriate educational and career opportunities and that to refuse their request is a denial of their rights as parents. Similarly, parents may request testing to clarify the status of young healthy children at risk of being carriers of a recessive disorder such as cystic fibrosis. Sometimes this information will have become available as a result of prenatal diagnostic testing.

The problem with agreeing to such a request is that it infringes the child’s own future autonomy. Increasingly, it is felt that testing should be delayed until the child reaches an age at which he or she can make his or her own informed decision. There is also concern about the possible deleterious effects on a child of growing up with the certain knowledge of developing a serious adult-onset hereditary disorder or being a carrier of a recessive disorder, particularly if the tests have proved negative in the child’s other siblings. Such a situation could raise a very real possibility of stigmatization. However, although there is consensus among geneticists that children should not be tested for carrier status, the evidence that such testing causes emotional or psychological harm is weak.

The situation is very different if predictive testing could directly benefit the child by identifying the need for a medical or surgical intervention in childhood. This applies to conditions such as familial hypercholesterolemia (p. 175), for which early dietary management can be introduced, and also to some of the familial cancer-predisposing syndromes (p. 225) for which early screening, and sometimes prophylactic surgery, is indicated. Generally, it is thought that in these situations genetic testing is acceptable at around the time when other screening tests or preventive measures would be initiated.

One of the arguments for not testing children for adult-onset disorders is that parents might view their child differently, perhaps prejudicially, in some way. This type of argument has been voiced in relation to the PGD cases that have selected embryos not only for their negative affection status for Fanconi anemia but also in order to be a potential stem-cell donor for their affected child—so-called ‘savior siblings’. Those objecting to this use of technology cite a utilitarian, or instrumental, attitude toward the child created in this way. Furthermore, the child so created has no choice about whether to be a tissue-matched donor for the sick sibling. Will the child eventually feel ‘used’ by the parents, and how might he or she feel if the treatment fails and the sick sibling dies? At present these questions are imponderables because most children created for this purpose are too young to tell how they feel—the first successful case was in the United States in 2000. The numbers of such children will be very small for the foreseeable future.

Implications for the Immediate Family (Inadvertent Testing or Testing by ‘Proxy’)

A positive test result in an individual can have major implications for close antecedent relatives who themselves may not wish to be informed of their disease status. For example, consider Huntington disease (HD), for which direct mutation analysis is available. A young man age 20 years requests predictive testing before starting his family; his fears are based on a confirmed diagnosis in his 65-year-old paternal grandfather. Predictive testing would be relatively straightforward were it not for the fact that his father, who is obviously at a prior risk of 1 in 2, specifically does not wish to know whether he will develop the disease.

Thus the young man has raised the difficult question of how to comply with his request without inadvertently carrying out a predictive test on his father. A negative result in the young man leaves the situation unchanged for his father. However, a positive result in the son might be difficult to conceal from an observant father; and the son will know that his father will develop the disease if he has not done so already.

There is no easy solution to this particular problem. In the guidelines drawn up in 1994 for predictive testing in HD it was concluded that ‘every effort should be made by the counselors and the persons concerned to come to a satisfactory solution’, with the rider that ‘if no consensus can be reached the right of the adult child to know should have priority over the right of the parent not to know’.

Implications for the Extended Family

It is widely agreed that the identification of a condition that could have implications for other family members should lead to the offer of tests for the extended family. This applies particularly to balanced translocations and serious X-linked recessive disorders. In the case of translocations, this is sometimes referred to as translocation chasing. For an autosomal recessive disorder such as cystic fibrosis, the term ‘cascade screening’ is applied (p. 304).

The main ethical problem that arises here is that of confidentiality. A carrier of a translocation or serious X-linked recessive disorder is usually urged to alert close family relatives to the possibility that they could also be carriers and therefore at risk of having affected children. Alternatively, permission can be sought for members of the genetics team to make these approaches. Occasionally a patient, for whatever reason, will refuse to allow this information to be disseminated.

Faced with this situation, what should the clinical geneticist do? In practice most clinical geneticists would try to convince their patient of the importance of offering information and tests to relatives, possibly by providing an explanation of the consequences and ill-feeling that could arise in the future if a relative was to have an affected child whose birth could have been avoided. In most cases, skilled and sensitive counseling will lead to a satisfactory solution. Ultimately, however, many clinical geneticists would opt to respect their patient’s confidentiality rather than break the trust that forms a cornerstone of the traditional doctor-patient relationship. Not all would agree, and where the application of this standard could result in damage or morbidity to other family members, the clinician might seek to persuade the individual to disclose the medical/genetic information. This view is backed up by the statements of authoritative working parties, such as the Nuffield Council on Bioethics. Sometimes it is possible to draw the issue to the attention of the general practitioner of the family member at risk—he or she might be well placed to open the issue up in a sensitive way.

Informed Consent in Genetic Research

All individuals who agree to undergo genetic testing in a service context are obviously entitled to a full and clear explanation of what the test involves and how the results could have implications for both themselves and other family members. Vigorous efforts are usually made to ensure that these basic principles are adhered to, particularly when predictive testing for serious late-onset genetic disorders is being undertaken.

The issues relating to informed consent when participating in genetic research are just as complex. Many people are perfectly willing to hold out their arm for a blood test which might ‘help others’, particularly if they have personal experience of a serious disorder in their own family. However, few will have given any serious thought to the possible ramifications of their simple act of altruism. For example, it is unlikely that they will ever have considered whether their sample will be tested anonymously, who will be informed of the result, or whether other tests will be carried out on stored DNA in the future as new techniques are developed. These concerns, among others (Box 24.5), have prompted the US National Institutes of Health Office of Protection from Research Risks to draw up proposals on the steps that should be taken to try to ensure that all aspects of informed consent are addressed when samples are collected for genetic research. Just as signed consent for genetic testing and storage of DNA has become routine in the service setting (although not a legal requirement under the UK Human Tissue Act 2004), similar procedures should be adhered to in a research setting.

Genetics and Insurance

The availability of predictive tests for disorders of adult onset that convey a risk for chronic ill health, and possibly reduced life expectancy, has led to concern about the extent to which the results of these tests should be revealed to outside agencies, especially insurance companies providing life cover, private health care, and critical illness and disability income. For insurance arranged through an employer, in theory adverse genetic tests might compromise career prospects.

The life insurance industry is competitive and profit driven. Private insurance is based on ‘mutuality’, whereby risks are pooled for individuals in similar circumstances. In contrast, public health services are based on the principle of ‘solidarity’, whereby health provision for everyone is funded from general taxation. It is understandable that the life insurance industry is concerned that individuals who receive a positive predictive test result will take out large policies without revealing their true risk status. This is sometimes referred to as ‘antiselection’ or ‘adverse selection’. On the other hand, the genetics community is concerned that individuals who test positive will become victims of discrimination, and perhaps uninsurable. This concern extends to those with a family history of a late-onset disorder, who might be refused insurance unless they undergo predictive testing.

The possibility that DNA testing will create an uninsurable ‘genetic underclass’ led to the introduction of legislation in parts of the United States aimed at limiting the use of genetic information by health insurers. In 1996 this culminated in President Clinton signing The Health Insurance Portability and Accountability Act, which expressly prevented employer-based health plans from refusing coverage on genetic grounds when a person changes employment. In the United Kingdom, this whole arena was considered in 1995 by the House of Commons Science and Technology Committee, which recommended that a Human Genetics Advisory Commission be established to overview developments in human genetics. In 1997 this Advisory Commission (subsumed into the Human Genetics Commission which was abolished in 2010) recommended that applicants for life insurance should not have to disclose the results of any genetic test to a prospective insurer and that a moratorium on disclosure of results should last for at least 2 years until genetic testing had been carefully evaluated.

Inevitably, the Association of British Insurers (ABI) had a view. In the 1999 revision of its Code of Practice, the ABI reiterated its view that applicants should not be asked to undergo genetic testing and that existing genetic test results need not be disclosed in applications for mortgage-related life assurance up to a total of £100,000. In 2005 the UK government negotiated an agreement with the ABI to extend restriction on the use of predictive genetic tests by insurers to November 2011. The document, entitled ‘Concordat and Moratorium on Genetics and Insurance’ (Box 24.6), stated that no one will be required to disclose the result of a predictive genetic test unless first approved by the government’s Genetics and Insurance Committee (GAIC). The GAIC approved only one application—for HD for amounts greater than £500,000—and the body was abolished in 2009.

These issues are likely to come under renewed scrutiny in the future. Where various combinations of polymorphisms convey susceptibility to common disorders of adult life, large swathes of the population could find themselves at the mercy of a profit-driven, commercially-focused insurance industry. The medical genetics community therefore has an advocacy role to ensure that the genetically disadvantaged, through no fault of their own, do not face discrimination when seeking health care or long-term life insurance. These are powerful arguments favoring retention of the principles of the UK National Health Service.

Forensic Science and DNA Databases

The existence of the police-controlled National DNA Database in the UK has been hotly debated as an issue of personal privacy. The use of DNA fingerprinting in criminal investigations, to the tune of approximately 10,000 cases per annum, is now so sophisticated that there is a natural desire on the part of law enforcers to be able to identify the DNA fingerprint for anyone in the general population. Furthermore, techniques have been developed, called DNA boost, to generate profiles of individuals from samples where the DNA of two or more persons is mixed. The UK’s National DNA Database, which once contained material solely from sentenced offenders, has expanded rapidly and is now the largest of any country, containing information on more than 5 million people (0.8% of the population), including an estimated 1 million with no criminal conviction; this compares with 0.5% of the population in the United States. For certain types of crime, whole sections of a community are invited to come forward to give a sample of DNA so that they can be eliminated from enquiries. However, with significant numbers of DNA samples from children on the database, including that of at least one infant, the police came under political pressure in 2009 to scrap ‘innocent’ profiles after a declaration by the European Court of Human Rights that to hold the profiles of innocents indefinitely was a breach of privacy.

The National DNA Database is huge, but so too are the collections for big population studies, such as ALSPAC (Avon Longitudinal Study of Parents and Children) or the UK Biobank project. As research, these samples will have been rigorously consented, but it is essential for safeguards to be built into the use that is made of DNA collections such as these, and access to them. Debate will certainly continue on the use and misuse of personal genetic data.

Gene Patenting and the Human Genome Project

The controversy surrounding the patenting of naturally occurring human DNA sequences, whether complete genes or expressed sequence tags, neatly encapsulates the conflict between harsh commercial realism and altruistic academic idealism. As illustrations of the levels of investment, it is noteworthy that the rights to one gene associated with obesity were sold in 1995 for $70 million, whereas in 1997 DeCODE, the Icelandic genomics company at the center of the controversy regarding national assent, sold the potential rights to 12 genes, possibly associated with common complex diseases, to Hoffman-La Roche for $200 million. On the one hand, biotechnology companies that have invested heavily in molecular research can reasonably argue that they and their shareholders are entitled to benefit from the fruits of their labors. Biotechnology research is indeed expensive, and the realistic view is that commercial companies must at least cover their costs (otherwise they cease to exist) but preferably make a fair return on investments. The idealistic view argues that the human genome represents humankind’s ‘common heritage’ and that information gained through the Human Genome Project, or other molecular research, should be freely available for all to benefit, thus maintaining the ethical principle of equity of access. Proponents of the latter cite alleged exploitation of patients and communities who have donated their blood samples for research, little realizing that their generosity could be exploited for financial gain. This is amply illustrated by the furor surrounding the proposed use (or abuse) of a centralized medical database of the entire Icelandic population to help identify ‘polygenes’ for potential commercial gain. There have been some high-profile court cases over the issue in the United States.

The legal issues are complex and, not surprisingly, the international community has struggled to identify satisfactory solutions. With the exception of the United States, most national regulatory bodies prohibit payment for the procurement of human genetic material, but their views on patenting are much less well defined. In recent years many important human genes have been patented, and companies such as Myriad Genetics in the United States sought to impose their exclusive licence for genetic testing for BRCA1 and BRCA2 (p. 224). In fact, in 2004 the European Patent Office revoked the patent, denying Myriad a license fee from every BRCA test undertaken in Europe, and thereby setting a precedent for other contentious cases. Gene patents may concern single-gene disorders, such as the BRCA genes, but increasingly commercial companies are offering a range of ‘direct to consumer’ tests, consisting of the analysis of a range of polymorphisms, with the promise of predicting the future risk of ill health from common disorders. These companies are often less than candid about the precise tests offered, and their validation, all of which runs counter to the spirit of scientific enquiry and evidence-based medicine.

Gene Therapy

One of the most exciting aspects of recent progress in molecular biology is the prospect of successful gene therapy (p. 350), although it is obviously disappointing that this potential has not yet been realized. It is understandable that both the general public and the health care professions should be concerned about the possible side effects and abuse of gene therapy. Frequent reference has been made to the ‘slippery slope’ argument, whereby to take the first step leads incrementally and inevitably to uncontrolled experimentation. To address these anxieties, advisory or regulatory committees have been established in several countries to assess the practical and ethical aspects of gene therapy research programs.

Concern centers around two fundamental issues. The first relates to the practical aspects of ensuring informed consent on the part of patients who wish to participate in gene therapy research. Adult patients and parents of children affected by otherwise incurable conditions may be desperate to participate in gene therapy research. Consequently they may disregard the possible hazards of what is essentially a new, untried, and unproven therapeutic approach. In the United Kingdom, the Committee on the Ethics of Gene Therapy recommended that, until shown to be safe, all gene therapy programs should be subjected to careful scrutiny by research ethics committees. In addition, a national supervisory body, the Gene Therapy Advisory Committee (GTAC), was established to review all proposals to conduct gene therapy in humans and to monitor ongoing trials, thus safeguarding patients’ rights and confidentiality.

Second, gene therapy generates concern about potential eugenic applications. The GTAC recommended that genetic modification involving the germline should be prohibited, and limited to somatic cells, to prevent the possibility of newly modified genes being transmitted to future generations. Somatic cell gene therapy should be used only to try to treat serious diseases, and not to alter human characteristics, such as intelligence or athletic prowess for example.

Population Screening

Population screening programs offering carrier detection for common autosomal recessive disorders, have been in operation for many years (p. 318), and in many cases well received (e.g., thalassemia and Tay-Sachs disease). This was not so with respect to neonatal screening for α₁ antitrypsin deficiency in Scandinavia, which was abandoned because it proved stressful. Such is the progress in comparative genome analysis that it will be technically possible to compare the genome of the unborn baby with that of its parents; de novo differences may represent mutations that would lead to serious disease and it has been proposed that the technique is offered to couples undergoing PGD. Chorionic villus tissue could also be analyzed in this way, and even free fetal DNA from maternal blood eventually. The ethical problem relates to the range of diseases that might be tested this way, and the choices couples might face.

With respect to screening programs that detect carrier status for disease, the issues are slightly different. Early efforts to introduce sickle-cell carrier detection in North America were largely unsuccessful because of misinformation, discrimination, and stigmatization. Also, pilot studies assessing the responses to cystic fibrosis (CF) carrier screening in white populations yielded conflicting results (p. 321). These experiences illustrate the importance of informed consent and the difficulties of ensuring both autonomy and informed choice. For example, CF screening in the United Kingdom has been implemented as part of neonatal screening. Although aimed at identifying babies with CF, the screening detects a proportion who are simply carriers, but obviously newborn infants cannot make an informed choice. Consequently, some pilot studies have focused on adults and their responses to the offer of carrier testing, either from their general practitioner or at the antenatal clinic. This has raised the vexed question of whether an offer from a respected family doctor could be interpreted as an implicit recommendation to participate, and such an approach yields a higher acceptance rate than a casual written invitation to attend for screening at a future date. This begs the question as to whether, depending on the approach, individuals feel pressured to undergo a test that they do not necessarily want.

It is, therefore, important that even the most well-intended offer of carrier detection should be worded carefully to ensure that participation is entirely voluntary. Full counseling in the event of a positive result is also essential to minimize the risk of any feeling of stigmatization or genetic inferiority.

In population screening, confidentiality is also important. Many will not wish their carrier status to be known by classmates or colleagues at work. The issue of confidentiality will be particularly difficult for individuals found by genetic testing to be susceptible to a medical problem through environmental industrial hazards, which could lead to employment discrimination (p. 367). These anxieties led in 1995 to the Equal Employment Opportunity Commission in the United States issuing a guideline that allows for anyone denied employment because of disease susceptibility to claim protection under the Americans with Disabilities Act.

Cloning and Stem Cell Research

Dolly the sheep, born in July 1996 at Roslin, near Edinburgh, was the first mammal to be cloned from an adult cell, and when her existence was announced about 6 months later, the world suddenly became intensely interested in cloning. Dolly was ‘conceived’ by fusing individual mammary gland cells with unfertilized eggs from which the nucleus had been removed; 277 attempts failed before a successful pregnancy ensued. It was immediately assumed that the technology would sooner or later lead to a cloned human being and there have been some unsubstantiated bogus claims to this effect. In fact, there has been widespread rejection of any move toward human reproductive cloning, with strong statements emanating from politicians, religious leaders, and scientists. Experiments with animals have continued to have a very poor success rate, and for this reason alone no rational person is advocating ‘experiments’ in humans. In some cloned animals, the features have suggested possible defects in genomic imprinting. Dolly died prematurely from lung disease in February 2003 and she had a number of characteristics suggesting she was not biologically normal.

Lessons have been learned from Dolly in relation to cell nuclear replacement technology and this has, potentially, opened the door to understanding more about cell differentiation. The focus has therefore shifted to therapeutic cloning using stem cells, and to the prospects this holds with respect to human disease. If stem cells were subjected to nuclear transfer from a patient in need, they might be stimulated to grow into any tissue type, perhaps in unlimited quantities and genetically identical to the patient, thus avoiding rejection. To date there have been a number of successes and the potential possibilities are legion for degenerative disease and repair of damage from trauma and burns.

The main ethical difficulty arises in relation to the source of stem cells. No one voices serious ethical difficulties in relation to stem cells harvested from the fully formed person, whether taken from the umbilical cord or the mature adult, and there have been significant advances using these sources. But a strong school of scientific opinion maintains that there is no substitute for studying embryonic stem cells to understand how cells differentiate from primitive into more complex types. In 2005 the UK Parliament moved swiftly to approve an extension to research on early human embryos for this purpose. Research on human embryos up to 14 days of age was already permitted under the Human Fertilization and Embryology Act 1990. The United Kingdom therefore became one of the most attractive places to work in stem-cell research because, although regulated, it is legal. Publicly funded research of this kind was not permitted in the United States until a change of political direction in 2009. Progress has been painfully slow for those engaged in this work, and the focus shifted to the creation of animal-human (‘human-admixed’) hybrids and chimeras because of the poor supply and quality of human oocytes (usually ‘leftovers’ from infertility treatment) for use in nuclear cell transfer. In the United Kingdom, Newcastle was granted a license to collect fresh eggs for stem-cell research from egg donors in return for a reduction in the cost of IVF treatment, a decision greeted with alarm in some quarters. This group was also the first, in 2005, to create a human blastocyst after nuclear transfer.

Those who object to the use of embryonic stem cells believe it is not only treating the human embryo with disrespect and tampering with the sanctity of life, but also could lead eventually to reproductive cloning. In fact, the Human Fertilization and Embryology Act of 1990 permits the creation of human embryos for research, but very few have been created since the HFEA began granting licenses. This Act of Parliament has been reviewed and updated to accommodate new developments, and came into effect in 2009. The main provisions are listed in Box 24.7 and will continue to generate contentious ethical debate.