Mr. and Mrs. A have recently had a baby son. They are both carriers of cystic fibrosis, although neither has the condition. Although they knew the risks of producing a child with cystic fibrosis, they decided to proceed with a pregnancy and now wish to know not only if their son has cystic fibrosis but also if he is a carrier.
Mrs. B attends her general practitioner wanting to be referred for a test for predisposition to breast cancer. Her mother had breast cancer and died at the age of 41. She is convinced that because of this family history she also may die prematurely, and she wishes to know the facts in planning her future life.
Although genetic testing and screening have a number of issues in common, they are different in their scope. Genetic “testing” applies to the determination of some genetic factor in an individual, whereas screening aims to ascertain the prevalence of such a factor in a population or population group where there is no evidence in advance that any particular individual has it (Danish Council of Ethics, 1993; Nuffield Council on Bioethics, 1993, 2006; Chadwick, 1998). Genetic testing is normally an issue when either an individual requests it, for example because of knowledge of a family history, or is referred by a medical practitioner. Screening programs, although they will involve actual testing of individuals, are typically part of a public health program, for example in response to a government-determined need to address a given health issue. Screening may take place at different stages of life – neonatal, childhood or adult – and may raise different associated questions. Context is also important: reproductive testing and screening, for example, are linked with particular sensitivities, especially in light of the history of genetics and its use and abuse in the form of eugenics. It is important to note, however, that genetic testing and screening may also form part of medical research protocols, for example to establish links between genetic factors and predisposition to disease or adverse responses to drugs.
The term “genetic test” is not entirely transparent. It has been defined as “a test to detect the presence or absence of, or change in, a particular gene or chromosome” (Nuffield Council on Bioethics, 2006), but it may or may not involve analysis of DNA. In some cases, examination of other substances such as the proteins produced in the body can indirectly provide genetic information. The term “genetic information,” however, also has a wider scope than that in the above definition of genetic test: it may include “data from the pedigree, the name of a genetic disorder, the genetic status of a family member (e.g., carrier/affected) or the result of a clinical or laboratory test” (Royal College of Physicians, 2006).
In the aftermath of the completion of the Human Genome Project, genetic testing and screening have, at least potentially, acquired much more power and taken on a new degree of complexity, increasing the likelihood of obtaining more useful genetic information in the testing and screening not only for presence of single gene disorders, but also for susceptibility to common disease, for behavioral traits (Nuffield Council on Bioethics, 2002), for propensity to suffer adverse drug responses (Nuffield Council on Bioethics, 2003; Roses, 2004), and to respond well or badly to foodstuffs (Chadwick, 2004; Food Ethics Council, 2005).
As more is discovered about the relationship between genetic factors and common disease, genetics will become more important to specialties apart from clinical genetics itself. Healthcare professionals in a wide variety of areas of medicine, although not conducting research themselves, may find themselves dealing with genetic information and its associated ethical issues, and they may have patients enrolled in research projects that have a genetic element or are participating in bio-banks (collections of biological samples, such as blood samples, for the purpose of establishing associations between genetic factors and health status such as susceptibility to disease, and/or to study variation in a population).
The ethical issues arising in relation to genetic testing and screening largely depend on the view that there is something special about genetic information which makes it different from other kinds of medical information. The features that make it special are that it has implications for family members other than the individual in question and that it is predictive and not specific to time. Although other kinds of medical information may share one or more of these features to some degree, and so it might be claimed that genetic information is not one of a kind, nevertheless these features are important in addressing the ethical issues and they are relevant to both testing and screening.
The fact that genetic information is shared with family members gives rise to issues about confidentiality and sharing of information (Human Genetics Commission, 2003). An individual may wish his/her test results to be confidential, whereas the health professional may consider it important that a relative has access to the information if it is relevant to the relative’s future health. There is, therefore, an issue for the health professional as to whether to disclose or not, if the patient is unwilling to share the information.
The predictive nature of genetic information indicates that there is an important distinction between types of testing; whereas some diagnose an existing condition, others may be predictive of future health status. Testing an individual for whether he or she has a particular disorder can be helpful either for identifying a course of action or simply for offering relief where anxiety has been caused by not knowing. Where predictive testing is concerned, however, whether for predisposition to a late-onset disorder or for susceptibility to common disease, the issues are more complicated. Uncertainty over the accuracy of the test results and how they are to be interpreted is an issue, as people may make life-changing decisions on the basis of test results, perhaps becoming fatalistic although it is not certain that they will actually develop a condition (e.g., heart disease) or how severe it will be. Where children are concerned, testing them for a late-onset disorder, especially one for which there is currently no treatment available (e.g., Huntington’s disease), may cause them positive harm such as stigmatization (Clarke, 1998). There has also been concern that predictive information might be used by third parties such as insurance companies or employers to the detriment of individuals: for example raising premiums or denying insurance or employment to people on the basis of a higher risk of developing a particular disorder (Nuffield Council on Bioethics, 1993; European Group on Ethics in Science and New Technologies, 2003; UK Government and Association of British Insurers, 2005).
The third feature of genetic information mentioned, that it is not specific to time, facilitates its long-term storage for future analysis, as new associations and testing techniques are discovered. This has led to the setting up of bio-banks in different countries as research tools to enable associations to be made between genetic factors and health status, providing information about variation within the population (Häyry et al., 2007). These initiatives are not typically justified on the basis of benefit to the individual donor of a sample but on the basis of public good or public health, as is the case in screening programs. Practice varies, however, on the extent to which an individual participant may expect to receive information revealed about their own genetic constitution.
Because of the disadvantages that might accrue to people on the basis of genetic test results, some have argued for the individual’s “right not to know” information about their genetic constitution, and consent to have a sample taken for testing is thus a central ethical issue (Chadwick et al., 1997). Questions arise both as to who may consent (e.g., in the case of childhood testing) and as to what information is provided and how (e.g., is some form of genetic counseling necessary?) (Nuffield Council on Bioethics, 1993). Where long-term storage is an issue, there are further questions about narrow or broad consent to future uses of the sample: whether recontacting of the donor is necessary at different stages.
The range of possible applications of genetic information is vast, and there will be national differences in the ways in which different countries regulate in this area (Cutter et al., 2004). For example, whereas in some countries (e.g., Iceland) national bio-banks are rooted in legislation, in others they are not (e.g., UK). As regards clinical practice, preexisting common law and/or legislation concerning consent and the use and disclosure of medical information will apply unless there has been specific legislation concerning genetic information and its applications. There are also some international instruments that have to be taken into consideration.
The Universal Declaration on the Human Genome and Human Rights (UNESCO, 1997), although it has no legal force, lays down certain principles such as the right of everyone to respect for their dignity and rights regardless of their genetic characteristics, and it provides that genetic data must be held in conditions of confidence. The Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine (Council of Europe, 1997) also enunciates some general principles. It provides, for example, that tests which are predictive of genetic disease or which serve to identify a person as a carrier of a gene responsible for disease or to detect a genetic predisposition or susceptibility to a disease may be performed only for health purposes or for scientific research linked to health purposes and should be subject to appropriate counseling.
In some jurisdictions preexisting law relating to consent has been deemed to be insufficient. For example in the UK, under the Human Tissue Act 2004, a new offence of non-consensual analysis of DNA has been established. Although the intention is not to prevent use of DNA for medical or research purposes, it addresses concerns over the possibility of its malicious use. The Act does not apply to all material from the human body (it excludes, for example, gametes and embryos outside the body and dried blood spots), but it provides a legal framework for the removal and use of tissue, including the requirements of consent such as who can give “qualifying consent” for analysis of DNA in cellular tissue. Consent is not required for use of cellular material in the diagnosis and treatment of the donor, and this has led to concern that this could facilitate future use of screening without consent, although the Nuffield Council on Bioethics (2006) noted that the requirements of consent for use of personal data as laid down in the Data Protection Act 1998 apply. This Act regulates the obtaining, holding, use, or disclosure of personal information.
In both the UK and the USA, there is specific legislation concerning disabilities and discrimination, the Disability Discrimination Act 1995 and the Americans with Disabilities Act 1990, respectively, which may be relevant in the context of genetics. The question arises and debate continues as to how disability is defined, specifically as to whether it could or should include persons with a presymptomatic genetic disorder.
In a field where scientific knowledge tends to advance very rapidly, legislation is not always the governance mode of choice, and a variety of policy-making bodies and advisory committees have emerged. At international level, for example, the Human Genome Organisation (HUGO) Ethics Committee has issued a number of statements dealing with issues in genetics, starting with the Statement on the Principled Conduct of Genetic Research in 1996 (Human Genome Organisation, 1996). The statements are largely concerned with research, although they have wider relevance in so far as they touch on issues such as the collection of DNA samples (Human Genome Organisation, 1998). This is a field, however, in which ethical frameworks develop and change as well as the science, and in its recent statements the HUGO Ethics Committee has tended to emphasize considerations such as solidarity and equity, in addition to the long-standing concerns of individual consent and confidentiality (Knoppers and Chadwick, 2005). The move away from the centrality of the individual, however, has also made its mark on practice, with the suggestion of models such as the “joint account” to represent the family’s shared ownership of genetic information (Parker and Lucassen, 2004).
In the light of the complexity of the issues, some committees or commissions have produced major and influential reports on topics such as genetic screening. For example, the Nuffield Council on Bioethics, which issued its report Genetic Screening: Ethical Issues in 1993, has produced a supplement on developments since then (Nuffield Council on Bioethics, 2006). The supplement noted the danger of overexaggerating the promises of genetics and takes the view that some of the purported benefits are still some way off, including screening for polygenic diseases and realizing the benefits of pharmacogenomics, which studies links between genetic factors and drug response to facilitate genetically informed drug prescribing and to reduce the number of adverse drug responses. Also in the UK, the National Screening Committee (2003) has developed criteria for the introduction of genetic screening programs, which include considerations related to the nature of the condition screened for and what can be done in the light of a positive result. General guidelines have also been issued relating to consent, where the prevailing principles reflect the need for consent both to obtain a DNA sample and to disclose the information contained therein (Royal College of Physicians, 2006).
In genetics, different kinds of empirical study are at issue, such as different association studies to establish links between genetic factors and disease and other characteristics of individuals. Association studies may be disease specific or concerned with human variation with a population, as in the UK bio-bank.
In the ethical context, however, empirical studies within the social sciences have taken on special importance because of concerns about public perception of genetics. Worries that opposition to genetically modified food might be mirrored by unwillingness to accept genetically informed medicine such as pharmacogenomics has led to the perceived need to undertake a wide range of initiatives in public engagement. While this might be viewed from an instrumental point of view, as designed to achieve public acceptance, it is now widely recognized that a one-way process of “informing” is inadequate, and listening to people’s concerns is equally if not more important so that public policy can be appropriately shaped by awareness of these. Work on attitudes towards pharmacogenomics in the north west of England, for instance, has shown appreciation of its potential benefits, including faster access to a suitable drug, in place of trial and error, and more personalized side effect profiles, while there is concern among health professionals about the possible withholding of a drug on the basis of pharmacogenomic information (Fargher et al, 2006).
In the context of clinical genetics, the above issues have received a high degree of discussion and debate over the last 10 years in particular. It is arguably outside this context where guidance is needed. While there is an abundance of detailed guidance on approaching the issues, there are some common themes that need to be borne in mind.
Firstly, best practice on consent suggests that obtaining consent to donate a sample should be documented, along with information as to what current and future uses the consent covers (Royal College of Physicians, 2006). Secondly, with regard to confidentiality of the information, while there is a view that in some exceptional cases a healthcare professional should have discretion to disclose to family members where there may be risk of a serious condition and treatment is possible (e.g., in the case of colon cancer; Genetic Interest Group, 1998), such cases would be very rare, the balance of harms test is not an easy one to assess. The importance of confidentiality has been reiterated in recent discussions (see Nuffield Council on Bioethics, 2006; Royal College of Physicians, 2006).
Thirdly, there is a set of issues arising from the uncertainty of much of the information, the perception of risk information, and the hype surrounding genetic information (as well as the exaggeration of possible disadvantages). These considerations lead to the need in practice to have effective communication aiming to generate realistic expectations.
In the first case, there is an issue as to who has authority to consent to the genetic testing of a child, and whether that testing is in the child’s interests. There is an important distinction to be made between diagnostic and predictive testing here. It is widely accepted that children should only be tested where it is in their interests and some treatment can be offered, and that they should not be tested for a late-onset disorder. It is far from clear that it is in the interests of the child that it be disclosed to the parents whether or not he/she is a carrier. While this will be important to the child on reaching adulthood, in making his or her reproductive decisions, there is no obvious scope for immediate appropriate action and so the testing should not be carried out. In cases of testing of children, an additional complication may be that the test result will show that the male partner of the couple is not in fact the genetic parent, and then there will be issues of confidentiality of the mother versus the father’s right to know, although this is not an issue in this case.
In the second case, Mrs. B may be a good candidate for testing for the BRCA1 and BRCA2 mutations, which confer a higher risk of breast cancer. More information about the family history needs to be obtained. It may be that she is being overfatalistic in thinking that her life path will have the same outcome as that of her mother. Interpretation of information is important. It needs to be made clear to her that a negative result does not mean that she will be free from risk of breast cancer, as the majority of breast cancers are not caused by BRCA1 and BRCA2. What the options are in the light of a positive result also need to be discussed, in terms of types of therapy or preventive action available, including preventive mastectomy. The potential implications for other family members in the light of a positive result need to be considered, for example the interest her sister might have in this information. Mrs. B should be encouraged to discuss the situation with her sibling.
The author gratefully acknowledges the support of the Economic and Social Research Council; the work described was part of the programme of its Research Centre for Economic and Social Aspects of Genomics.