Genetics and prevention: a policy in the making

Abstract

This article explores the processes through which the advances of genetic research are incorporated into public health care in Denmark. Drawing on ethnographic fieldwork in cancer genetic counselling, the implementation of new medical advances is investigated by following the establishment of a policy on informing relatives at risk of hereditary cancer. This case material provides the occasion to examine how policies are shaped in a governmental process through which different actors seek to establish a common goal for a specific health practice. The struggle to define such a goal implies a struggle to define where to draw the line between health and disease and what makes up a healthy person in the context of genetic knowledge. The authors argue that in the process of establishing a policy in the field of cancer genetics the imperative of prevention comes to provide the framework within which an ethics of rights and responsibilities is constituted and the target group of cancer genetic counselling defined. This ethics is not determined by or inherent in genetic technology itself, but constituted in a social process and therefore negotiated within pre-existing frameworks of understanding in professional practice.     

Cancer genetics and its "different faces of autonomy"

In this article we discuss the development of a practice of screening, preventive treatment, and presymptomatic testing for individuals at risk of Familial Adenomatous Polyposis (FAP), a specific hereditary predisposition for colon cancer. We describe this development as a process of co-evolution, showing how this practice has been gradually taking shape in a new network of actors, routines, rules, institutions and technologies. We further argue that, looking at the emergence and transformation of this practice, we can distinguish two different regimes: a regime of prevention and a regime of self-determination. In each of these regimes the autonomy of patients and individuals at risk is shaped in a different way, that is, through a different complex of ideals, procedures, institutions, technologies, and routines. In our view, the interference between these two regimes is an important characteristic of the emergent new genetics and is reflected in the growing debate about non-directivity in genetic counselling. However, as our argument implies, when facing the challenges of the new genetics we should not restrict the debate to the quality and ethics of counselling, but extend our view to the whole complex of elements and activities which shapes individual autonomy in the context of different regimes.     

Ethics and practice: two worlds? The example of genetic counselling

The aim of this paper is to work out the relationship between ethics and practice with reference to genetic counselling. First, the most important principles with respect to genetic counselling and to counsellor-client-interaction, are explained briefly. Then, we discuss what these principles might mean, when applied to the practice of counselling. To do so, we also look at some empirical data. Finally, we draw some conclusions.     

The emerging role of the physician in genetic counselling and testing for heritable breast,ovarian and colon cancer.

As a genetic testing for susceptibility to breast, ovarian and colon cancer becomes more readily available, physicians are faced with an increasing demand for information about inherited cancer risk. Because advances in treatment have not kept pace with advances in predictive testing, the provision of genetic counselling and testing marks a departure from the traditional role of the physician. A systematic framework is needed within which the physician''s emerging role in predictive testing for heritable cancer can be delineated. The development of such a framework will require collaboration among professionals in a range of scientific disciplines, as well as the suspension of traditional assumptions about the physicians role.     

Women's need for information before attending genetic counselling for familial breast or ovarian cancer: a questionnaire,interview, and observational study.

OBJECTIVES: To describe women''s information needs prior to genetic counselling for familial breast or ovarian cancer. DESIGN: Prospective study including semistructured telephone interviews before genetic counselling, observations of consultations, completion of postal questionnaires, and face-to face interviews within two months of counselling. SUBJECTS: 46 women attending genetic counselling for familial breast or ovarian cancer. MAIN OUTCOME MEASURES: Subjects'' understanding of process and content of genetic counselling before attending and attitudes about their preparation for the counselling session. RESULTS: Although all women interviewed before the clinic expected to discuss their risk of developing cancer and risk management options, there was evidence of a lack of knowledge about the process and content of genetic counselling, 17 (37%) women said they did not know what else would happen. Most women interviewed after counselling viewed it positively, but 26 (65%) felt they had been inadequately prepared and 11 (28%) felt that their lack of preparation meant that they could not be given an accurate estimation of their risk of cancer. CONCLUSIONS: Some women felt that they did not obtain optimum benefit from genetic counselling because they were inadequately prepared for it. We suggest that cancer family history clinics should provide women with written information about the process and content of genetic counselling before their clinic attendance.     

Genetic counselling and testing for susceptibility to breast,ovarian and colon cancer: where are we today?

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.     

Human genome research and the public interest: progress notes from an American science policy experiment.

This essay reviews the efforts of the U.S. Human Genome Project to anticipate and address the ethical, legal, and social implications of new advances in human genetics. Since 1990, approximately $10 million has been awarded by the National Institutes of Health and the Department of Energy, in support of 65 research, education, and public discussion projects. These projects address four major areas of need: (1) the need for both client-centered assessments of new genetic services and for improved knowledge of the psychosocial and ethnocultural factors that shape clients' clinical genetic experiences; (2) the need for clear professional policies regarding human-subject research, clinical practice standards, and public health goals in human genetics; (3) the need for social policy protection against unfair access to and use of personal genetic information; and (4) the need for improved public and professional understanding and discussion of these issues. The Human Genome Project's goal is to have defined, by 1995, policy options and programs capable of addressing these needs.     

Ethical issues in translational research

The translation of biomedical research knowledge to effective clinical treatment is essential to the public good and is a main focus of current health policy. However, recent health policy initiatives intended to foster the translation of basic science into clinical and public health advances must also consider the unique bioethical issues raised by the increased focus on translational research. Safety of study participants and balancing of risk due to treatment with the potential benefits of the research is tantamount. This article synthesizes theory from clinical ethics, operational design, and philosophy to provide a bioethical framework for the health policy of translational research.     

High theory/mass markets: Newsweek magazine and the circuits of medical culture

Medicine is driven by much more than science and reason (ethics); it is also driven by the circuits of culture within which it operates. This article examines how postmodern theory deconstructs standard ideals of science and reason and allows medical humanities scholars to better contextualize the world of medicine. As such, postmodern theory provides an invaluable tool for understanding the circuits of popular culture and medicine's place within these circuits. Using a recent issue of Newsweek magazine devoted to health and technology to illustrate the main points, this essay argues that contemporary popular influences on medicine are deeply problematic, and that through an appreciation of the dynamics of culture, medical humanities scholars can join the struggle over medical culture. This perspective allows medical humanities to make important contributions toward alternative circuits of medical representation, consumption, and identification.     

Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy

The goal of cancer pharmacogenomics is to obtain benefit from personalized approaches of cancer treatment and prevention. Recent advances in genomic research have shed light on the crucial role of genetic variants, mainly involving genes encoding drug-metabolizing enzymes, drug transporters and targets, in driving different treatment responses among individuals, in terms of therapeutic efficacy and safety. Although a considerable amount of new targeted agents have been designed based on a finely understanding of molecular alterations in cancer, a wide gap between pharmacogenomic knowledge and clinical application still persists. This review focuses on the relevance of mutational analyses in predicting individual response to antitumor therapy, in order to improve the translational impact of genetic information on clinical practice.     

Ethical implications of genetic analysis of individual susceptibility to diseases

Ethics can be regarded as a reflection or reconsideration of existing moral codes in the search of good and goes beyond moral conduct. This means that ethics is a never-ending process, which in science must develop with the development of science itself. Thus, the process of seeking better ethics is as integral within science as the development of new methods. Along these lines of thought it can be argued that (1) poor science cannot be ethically sound, (2) every scientist has a personal responsibility to develop ethics in his area of expertise, (3) the development of solid ethical background in science requires education in ethics as well as in methodology and scientific thinking and (4) research ethics cannot develop in solitude, but needs input from other scientists, other fields (including philosophy) and society. Several burning questions can be identified within genetic analysis for individual susceptibility. These ethical aspects can be viewed from three different perspectives: practice of research, patient/research subject personally and long-term implications in society. This paper tries more to awaken thoughts than give clear answers.     

A Not-So-Gentle Refutation of the Defence of Homeopathy

In a recent paper, Levy, Gadd, Kerridge, and Komesaroff attempt to defend the ethicality of homeopathy by attacking the utilitarian ethical framework as a basis for medical ethics and by introducing a distinction between evidence-based medicine and modern science. This paper demonstrates that their argumentation is not only insufficient to achieve that goal but also incorrect. Utilitarianism is not required to show that homeopathic practice is unethical; indeed, any normative basis of medical ethics will make it unethical, as a defence of homeopathic practice requires the rejection of modern natural sciences, which are an integral part of medical ethics systems. This paper also points out that evidence-based medicine lies at the very core of modern science. Particular arguments made by Levy et al. within the principlist medical ethics normative system are also shown to be wrong.     

Health care ethics and health law in the Dutch discussion on end-of-life decisions: a historical analysis of the dynamics and development of both disciplines

Over the past three or four decades, the concept of medical ethics has changed from a limited set of standards to a broad field of debate and research. We define medical ethics as an arena of moral issues in medicine, rather than a specific discipline. This paper examines how the disciplines of health care ethics and health care law have developed and operated within this arena. Our framework highlights the aspects of jurisdiction (Abbott) and the assignment of responsibilities (Gusfield). This theoretical framework prompted us to study definitions and changing responsibilities in order to describe the development and interaction of health care ethics and health law. We have opted for the context of the Dutch debate about end-of-life decisions as a relevant case study. We argue that the specific Dutch definition of euthanasia as 'intentionally taking the life of another person by a physician, upon that person's request' can be seen as the result of the complex jurisdictional process. This illustrates the more general conclusion that the Dutch debate on end-of-life decisions and the development of the two disciplines must be understood in terms of mutual interaction.     

The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information

Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An ‘ethic of care’ interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent.     

The genesis of public health ethics

As bioethics emerged in the 1960s and 1970s and began to have enormous impacts on the practice of medicine and research – fuelled, by broad socio‐political changes that gave rise to the struggle of women, African Americans, gay men and lesbians, and the antiauthoritarian impulse that characterised the New Left in democratic capitalist societies – little attention was given to the question of the ethics of public health. This was all the more striking since the core values and practices of public health, often entailing the subordination of the individual for the common good, seemed opposed to the ideological impulses of bioethics. Of what relevance is autonomy‐focused bioethics for public health, with its mix of justifications including those that are either implicitly or explicitly paternalistic or that seek to impose strictures on individuals and communities in the name of collective welfare? To examine the deep divide between the central commitments of bioethics and the values that animate the practice of public health, we focus on a series of controversies implicating the concepts of privacy, liberty, and paternalism. Recognising the role of moral values in decision‐making was a signal contribution of bioethics in its formative period. Over the past three decades a broad array of perspectives emerged under the rubric of bioethics but individualism remains central. As we commence the process of shaping an ethics of public health, it is clear that bioethics is the wrong place to start when thinking about the balances required in defence of the public's health.     

Genetic diversity and disease susceptibility.

The range of genetic diversity within human populations is enormous. Genetic susceptibility to common chronic disease is a significant part of this genetic diversity, which also includes a variety of rare clear-cut inherited diseases. Modern DNA-based genomic analysis can now routinely lead to the identification of genes involved in disease susceptibility, provides the basis for genetic counselling in affected families, and more widely for a genetically targeted approach to disease prevention. This naturally raises problems concerning the use of information on an individual''s decisions, but for employment, and health and life insurance.     

Application of biomarkers in cancer risk management: evaluation from stochastic clonal evolutionary and dynamic system optimization points of view

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic "biomarkers" have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time.     

Digitally supported public health interventions through the lens of structural injustice: The case of mobile apps responding to violence against women and girls

Mobile applications (apps) have gained significant popularity as a new intervention strategy responding to violence against women and girls. Despite their growing relevance, an assessment from the perspective of public health ethics is still lacking. Here, we base our discussion on the understanding of violence against women and girls as a multidimensional, global public health issue on structural, societal and individual levels and situate it within the theoretical framework of structural injustice, including epistemic injustice. Based on a systematic app review we previously conducted, we evaluate the content and functions of apps through the lens of structural injustice. We argue that technological solutions such as apps may be a useful tool in the fight against violence against women and girls but have to be situated within the broader frame of public health that considers the structural dimensions of such violence. Ultimately, the concerns raised by structural injustice are—alongside key concerns of safety, data privacy, importance of human supportive contact, and so forth—crucial dimensions in the ethical assessment of such apps. However, research on the role and relevance of apps as strategies to address the structural and epistemic dimensions of violence remains scarce. This article aims to provide a foundation for further discussion in this area and could be applicable to other areas in public health policy and practice.     

Research versus practice: The dilemmas of research ethics in the era of learning health‐care systems

In this article we attempt to answer the question of how the ethical and conceptual framework (ECF) for a learning health‐care system (LHS) affects some of the main controversies in research ethics by addressing five key problems of research ethics: (a) What is the difference between practice and research? (b) What is the relationship between research ethics and clinical ethics? (c) What is the ethical relevance of the principle of clinical equipoise? (d) Does participation in research require a higher standard of informed consent than the practice of medicine? and (e) What ethical principle should take precedence in medicine? These questions allow us to construct two opposite idealized positions on the distinction between research and practice: the integration model and the segregation model of research and practice. We then compare the ECF for an LHS with these two idealized positions. We argue that the ECF for a LHS does not, in fact, solve these problems, but that it is a third, separate position in the relationship between research ethics and clinical ethics. Moreover, we suggest that the ECF for a LHS raises new ethical problems that require additional ethical analysis and justification. Our article contributes to the discussion on the relationship between research ethics and clinical ethics, revealing that although a learning health‐care system may significantly change the landscape of health care, some ethical dilemmas still require resolving on both theoretical and policy‐making levels.     

Cystic fibrosis carrier testing in early pregnancy by general practitioners.

OBJECTIVE--To assess the feasibility of genetic counselling in general practice by using cystic fibrosis carrier screening at the booking appointment as an integral part of routine antenatal care and as a paradigm for the wider participation of general practitioners in medical genetics. DESIGN--Maternal testing (male partner tested only if woman screens positive) and couple testing for cystic fibrosis carrier status in the antenatal population attending one general practice and, later, in a further six (outreach) practices also. SETTING--Two partner urban training practice (pilot practice) in south Manchester, and six north west practices (two inner city, three urban, one rural dispensing). SUBJECTS--Total practice population of 50,000 (pilot practice plus six outreach practices) with an estimated 500-800 pregnancies per year. MAIN OUTCOME MEASURES--(a) Proportion of carriers of cystic fibrosis identified, counselled, and appropriately managed within the first trimester of pregnancy; (b) questionnaire and interview measures of patient satisfaction and stress. RESULTS--Eleven carriers of cystic fibrosis were detected including one carrier couple. This carrier couple, after extensive counselling, elected to have prenatal diagnosis by chorionic villus biopsy. The fetus was homozygous normal. CONCLUSIONS--General practitioners can successfully integrate genetic counselling and cystic fibrosis carrier screening into the first antenatal booking appointment. When a carrier couple is identified clinical geneticists can help with the discussion of reproductive options, and prenatal diagnosis by chorionic villus biopsy can be completed within the first trimester. The results suggest that general practitioners will have an increasingly important role in medical genetics, subject to continuing evaluation of patient acceptability and stress.