Ethical Issues of Human Genetic Databases

A Challenge to Classical Health Research Ethics?

Bernice Elger

• Publisher: Routledge
• Year: 2016
• ISBN:
  9781317141457
• Edition: 1
• Topic: Law
• Subtopic: Jurisprudence
• Index: Law

Following the boom in population databases in recent years there has been sustained and intense international debate about political processes and legal and ethical issues surrounding the protection and use of genetic data. As a result, several national and international organizations and committees have published widely differing guidelines and statements concerning genetic databases and biobanks. Ethical Issues of Human Genetic Databases compares the new area of biobanking with the tradition of ethically accepted classical research and highlights the distinctive features of existing databases and guidelines. The volume identifies areas of consensus and controversy while investigating the challenges posed to classical health research ethics by the existence of genetic databases, analyzing the reasons for such varying guidelines. The book will be essential to academics, biobankers, policy-makers and researchers in the field of medical ethics.

Chapter 1
Introduction

General Background

In 2003, the human genome project was completed. The human genome was entirely sequenced (Little et al. 2003). A consortium of universities and pharmaceutical companies has been analysing genetic variations related to susceptibility to diseases (Greenhalgh 2005; Knudsen 2005). The challenge has not changed since 2003: it is to match genotypes against phenotype and survival in the real world (Radford 2003). Indeed, many common diseases are believed to result from a combination of defects in multiple genes and lifestyle, biographical or other environmental factors (Sensen 2005; Mikail 2008, 71–9). Environmental factors comprise lifestyle-related issues such as exercise, diet and smoking, reproductive and demographic aspects, as well as exposure to infectious agents, pollution or other environmental hazards. The technical possibilities of automated data analysis of DNA samples and their bioinformatic processing have developed dramatically over the last few years and are constantly being improved (Allore 2007). They provide important new possibilities for this type of medical research. The combination of health and genetic data on large populations promises to deliver new insights about interactions between genes and environmental factors (Burton et al. 2009). In addition, the new discipline of pharmacogenetics explores the genetic idiosyncrasies of drug metabolism in individual patients that explain why some develop severe side effects to useful medications and others do not (Ashcroft and Hedgecoe 2006). Advanced knowledge in these areas becomes a prerequisite for a preventive and curative ‘personalized’ medicine providing maximum efficacy with minimal side effects (Gurwitz, Lunshof and Altman 2006; Lunshof, Pirmohamed and Gurwitz 2006).

Scientists and the pharmaceutical industry place great hopes in prospective population-based genetic studies (Breithaupt 2001; Brand and Probst-Hensch 2007). These hopes explain the population databases ‘boom’ observed during the past years (Kaiser 2002a, 1158–61).1 Various databases have been established or are planned, some on a national basis in Iceland, Estonia, Spain (Bosch 2004; Nys and Fobelets 2008), Croatia (Rudan et al. 2009), Taiwan (Fan, Lin and Lee 2008) and the UK (Barbour 2003; Elliott and Peakman 2008), others so far only including a county or region in Sweden (Austin, Harding and McElroy 2003a), the United States and Canada (Kaiser 2002a and 2002b). An example of a Swiss genetic database that has been approved by the cantonal ethics commissions of Zurich, Bern, Lucerne and Basel in 2002 and 2003 is the Swiss Pediatric Oncology Group (SPOG) Tumor Bank (Grotzer et al. 2003, 180–84).

In its summary of the most pressing issues raised by advances in genetic research, the 2002 Report of the World Health Organization’s (WHO) Advisory Committee on Health Research (ACHR) on Genomics and World Health states: ‘The planned development of large-scale genetic […] databases offers a series of hazards and ethical issues which have not been encountered before’ (The Advisory Committee on Health Research [ACHR] 2002, 26).

Iceland’s Act on a Health Sector Database (no. 139/1998) marks the beginning of a sustained and intense international debate about genetic databases. The political processes preceding these databases, as well as their particular legal and ethical arrangements, have stirred considerable controversies.2 In particular, it is the protection of genetic data collected in databases which has emerged as a highly complex ethical issue that has still not been addressed in an internationally satisfying way (Arnason, Nordal and Arnason 2004; Monsour 2007).

Ethical issues become even more acute when genetic data are combined with information on individuals’ health, lifestyle or genealogy, as is the case in major biobanks, for example, in the UK Biobank and the Icelandic Health Sector Database. The first combines genetic data with medical records and lifestyle information, and the second contains genetic data combined with medical records and genealogical information.

Ethical issues are sharpened in the international context (Benatar 2007; Capron et al. 2009), in particular when researchers and the populations being studied come from different cultural and socioeconomic backgrounds, such as in the Human Genome Diversity Project:

The HGD Project is an international effort to collect, preserve, analyze, and make available genetic and ethnographic information from people all around the world. The Project expects that its work will lead to advances in understanding the biological development and the history of our species and, ultimately, in understanding and treating many diseases with genetic components. The Project will collect DNA samples and ethnographic information from communities throughout the world, thus correcting the current bias in research in human genetics toward people of European descent. The Project expects that the samples will be preserved in repositories where they will be available to all qualified researchers. The samples will be analyzed, and the results of these analyses will be widely available through computerized databases. The Project is currently in its early stages and is still largely being planned (NARC 1997).

The boom of population databases (Kaiser 2002a) has been followed by a boom of different guidelines. Several national and international organizations and committees have recently published guidelines and statements concerning genetic databases and population biobanks. These guidelines differ considerably in their recommendations as regards some ethical problems.3

The following are the most important issues of controversy in the ethical debate and need further attention:

• Consent

Is the ‘opt-out’ model (which presumes consent to enter an individual’s data into a database unless the individual has explicitly refused) a morally acceptable solution?

Is individual consent a meaningful or sufficient concept when research will provide information on a family, group or population (including those who may have refused their consent, but are ‘indirect’ subjects of research)?

Can individuals give a ‘blanket consent’ concerning the future use of their samples, or do they have to be recontacted and asked for their consent each time a new research project is planned or the nature of an ongoing research project is changed?

• Confidentiality and access to the genetic databank

To what extent should databases be made secure enough to guarantee participants’ privacy, for example, should the government/the police or other third parties have access?4

Does society/the researcher/the company have a responsibility to avoid discriminatory effects (with regard to health insurance, employment, and so on) and to what extent?

Should access to repositories/databases be universal for all researchers or should some researchers have privileged access?

Should databases and resulting research findings be commercially exploited?

• Feedback to study participants

Should participants be informed about the results of the genetic tests performed on their data, and under what conditions should such feedback take place (for example, availability of genetic counselling)?

Should test results be transmitted to a participant if they indicate risks for diseases of which the participant was not aware?

• Benefit sharing

Should benefits be shared and what is to be considered a fair way of sharing?

More and more countries in Europe and North America, as well as in other continents (Sleeboom-Faulkner 2009), are addressing the problems presented by genetic databases: some countries have passed laws specifically regulating biobanks, as is the case, for example, in Iceland (Act on a Health Sector Database 1998) or Estonia (Eesti geenivaramu 2004c),5 and the list of countries considering and passing laws that contain sections explicitly addressing biobanks is steadily growing (Lindgren 2003; Elger 2006; Seoane and Da Rocha 2008); in others, like France (CCNE 2003),6 Germany (Nationaler Ethikrat 2004),7 Canada (CEST 2003),8 the UK (HGC 2002) and the US (National Bioethics Advisory Commission [NBAC] 1999), major national bioethics advisory committees have issued reports and position statements. However, the Steering Committee for Bioethics’ (CDBI) statement is still true today: ‘[L]egislative action in the field of research with human biological materials is still in its infancy both on a national and on an international level’ (CDBI 2002b).9

On the international level a few relevant documents already exist, while others are currently in preparation. The Declaration of Helsinki, until its revision in 2008, was relevant only in a general sense, laying out the ethical basis for research using human subjects. In 2008, under the influence of the boom of new guidelines, Helsinki added a new paragraph (para. 25) on ‘medical research using identifiable human material or data’ (WMA 2008).

In its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS 2002), which addresses general topics of research ethics, the Council for International Organizations of Medical Sciences provides some guidance on issues of confidentiality in genetic research (for example, guideline 18: Safeguarding confidentiality), but does not give a full account of the ethically problematic aspects of genetic databases.

The Council of Europe has issued an instrument on the use of human biological materials in biomedical research. This instrument contains general guidelines and more specific recommendations. It points out the necessity of practice guidelines, but the current document does not provide any.

Directive 95/46/EC of the European Parliament and the Council provides guidance on the protection of individuals with regard to the processing of personal data and on the free movement of such data, but it is not targeted towards genetic databases (European Parliament and the Council 1995). Its scope is limited to Europe.

Following a 2000 symposium, jointly sponsored with WHO in response to the debate on the Icelandic database, the World Medical Association (WMA) adopted in 2002 a Declaration on Ethical Considerations regarding Health Databases (WMA 2002). This document focuses on general principles of health databases and does not contain specific guidance for biobanks.

The UNESCO International Bioethics Committee has published an International Declaration on Human Genetic Data in 2003 (UNESCO 16 October 2003). The document provides a general normative framework in line with the human rights approach of UNESCO (Abbing 2004; Adalsteinsson 2004; Ten Have 2007), but does not elaborate on ethical problems arising at the technical and practical level.

The Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services of the WHO Human Genetics programme contains only a short chapter on genetic databases (WHO 1998). The WHO Handbook for Good Clinical Research Practice (WHO 2005) provides ethical background rather than targeted information on genetic databases and refers to future guidance: ‘Due consideration should be given to obtaining consent for the collection and/or use of biological specimens, including future purposes. Guidance is developing in this area’ (WHO 2005, 64). The WHO Handbook refers in this context to future guidance from CIOMS and the Council of Europe.

In comparison to the multitude of existing recommendations and guidelines, thorough ethical discussion in the literature is rather scarce, although the number of publications on selected issues concerning biobanks is growing steadily. As justification for their recommendations, many guidelines list a number of principles, including the ‘classical’ prima facie principles of autonomy, beneficence and justice (National Bioethics Advisory Commission [NBAC] 1999; UNESCO 16 October 2003), some very general principles that are used in different meanings, such as ‘human dignity’, and therefore judged useless by many ethicists,10 and new principles believed to be particular to the era of genetics, such as ‘genetic solidarity and altruism’ (HGC 2002, 37).

In the guidelines, the reasons for the different balancing of principles and its underlying values are in general not explicitly discussed. Several endeavours to present an ethically argued position on some of the issues have formulated the ethical issues in terms of morally legitimate interests (Buchanan 1999; Hansson 2001; Elger and Mauron 2003). The underlying reasoning is that principles and values reflect (and rights serve to protect) morally legitimate interests which need to be balanced in a way acceptable to the individuals and groups concerned. Defending a proper balance of the chief legitimate interests seems to be more promising than balancing principles, because, first, it can be shown that not all interests involved are of equal weight11 and, second, it becomes clear that it is not possible to satisfy and maximize all interests.

In conclusion, ethical problems concerning genetic databases have not so far been sufficiently discussed or resolved. Although the published recommendations mentioned above provide some guidance, no regulatory framework has been developed to date that (a) discusses in detail the controversial issues and the underlying ethical positions and argumentation, (b) is specific enough to provide practical guidance, and (c) is internationally accepted. There is a large national and international interest in resolving ethical problems related to biobanks.

In spite of the ethical controversy, new genetic databases continue to be established on a national and international level (Mitchell and Waldby 2009). They have different ethical frameworks and continue to capture political and ethical attention. The efforts of those who establish biobanks are important because promising research projects involve more and more cross-border flows of data and samples. The efficiency of the research, as well as the extent of potential risks to those who contribute their DNA to this type of biobank (Baumann 2001; Wichmann and Gieger 2007), will greatly depend on the development and implementation, first, of a global ethical framework and, second, of concrete practice guidelines that adapt the global framework to the needs of local research and health care institutions.

The Scope and Definitions

Many researchers, entrepreneurs who start to establish a biobank, as well as patients and active members of the community, continue to be perplexed by the highly controversial debate surrounding the ethical and legal issues concerning biobanks (Cavusoglu et al. 2008; Stege and Hummel 2008; Gibbons 2009). Given the rapid advances of biobanks and related biotechnology (Ennis et al. 2009), their promises and their risks, it is timely to present in more detail the controversial ethical issues related to research involving genetic databases. After more than 50 years of classical research ethics that are widely accepted in all part...

Table of contents

• Cover Page
• Title Page
• Copyright Page
• Contents
• List of Tables
• About the Author
• Foreword
• Acknowledgements
• 1 Introduction
• 2 Selected Existing Genetic Databases: Distinctive Features, Ethical Problems and the Public Debate
• 3 The Ethical Debate: Principles, Values and Interests – The Ethical Foundations of Guidelines
• 4 Selected Issues of Consensus and of Controversy
• 5 Ethical Issues of Human Genetic Databases and the Future
• References
• Index