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10th Forum of National Ethics Councils (NEC Forum) Lisbon 11 - 12 October 2007 DNA DATABASES: VALUES, INTERESTS, BENEFITS, RISKS1 Jorge Soares

On their seminal paper issued in Nature, James Watson and Francis Crick concluded, rather modestly, by saying that “DNA’ structure has novel features which are of considerable interest” (1). It was probably beyond their wildest imagination the discover impact. With the publication of the sequence and analysis of the human genome, almost 50 years later, scientists offered further evidence of how relevant this achievement was. We gained fresh insights into the miracle of life and we uncovered new mysteries that would occupy biomedical researchers for years to come. Genetic tests are currently available for the diagnosis of single-gene disorders or chromosome abnormalities, responsible for considerably rare diseases; however, there still exists a wrong public perception that, for most common diseases, only a single gene is involved (2). Unfortunately, the vast majority of common diseases that affect millions of people all over the world (e.g. hypertension) are genetically complex, their investigation involving DNA samples of large numbers of individuals, which justifies the need of tissue banks available for research. As an example, diabetes is a complex entity in which fifteen or more genes may be arranged in different combinations to originate the disease. Recent studies of identical twins also demonstrated and even reinforce that our genes are not all the determining factors of our human experience. Therefore, not only many genes are implicated in most of human so-called common diseases, but we know they also suffer even greater influence of environmental factors. A growing number of genetic tests are being designed for population-based applications, in two approaches: assessing the risk of developing a disease or condition in the future (e.g., predictive testing for breast cancer or cardiovascular disease), and attempting to identify genetic variations of the individual response to medicines (pharmacogenomics).

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Presented on the occasion of the 10º Forum of National Ethics Councils (NEC Forum), Lisbon, Portugal, 11 - 12 October 2007.

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As a consequence, there occurred a rapid expansion of what has been now called the social science of genomics, a new scientific domain for which human tissues collections for investigation are needed. Even before the announcement that the Human Genome Project was completed, the post genomic era was already taking shape. In Iceland, Britain, Estonia and other countries, plans were being put in place for the creation of human databases, considered to be the logical next step of the Human Genome Project. Aiming at obtaining scientific knowledge of multifactorial diseases and their treatments as well as individual reactions to pharmaceutical drugs, the creation of DNA databases is surrounded by controversy and debate with worldwide media attention and significant financial instruments, involving public and private institutions at national and international levels. The major reason for the controversy stands on the unique fact that genetic databases combine genetic information with personal data from the so-called common healthy people, looking, in that way, inside one of the most intimate part of ourselves. Then, relevant social interests, legal issues and ethical values have been implicated and potentially conflicting. Their complexity, involving privacy, confidentiality, informed consent, commercialization, ownership, governance of research, is magnified since people come to participate in genetic databases in a double condition: as donors of tissue samples and personal information; and as part of the public consultations in the construction and governance of projects. Which are, in brief, the benefits and the promises of the DNA databases, bringing together several streams of data about individuals: on molecular genetics, on health and illness clinical data, on lifestyles and environment and, in some cases, genealogical pedigrees? Scientists claim that the distinct functions of our known genes can therefore be elucidated as well as their relative prevalence in populations, and, socially more relevant, how they may predispose to or protect from illnesses, allowing adequate medical interventions. For the purpose of large-scale genetic research it came up the concept of population collection, a term coined around 2000. The main strategy that supports genetic databases is the search for correlations. The precision, with which genetic makeup can now be known, at reasonable cost and high speed, and its correlation with other complex information, using computer systems, is truly revolutionary (3). The databases can enrol distinct characteristics. They may be run as governmental, private or hybrid initiative, as well as national, regional and international. Some of them are related to the 2

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study of a specific diseases aiming at collecting as much information as possible of affected patients, frequently as part of a cooperative transnational study, whose ethical considerations are mostly related to individual acceptance of tissue donation. Different weight of the ethical values are associated to the whole population-based DNA banks (4). One of the most well known and controversial is the Icelandic health sector database, managed by the firm deCODE Genetics, into which general practitioners routinely deposit patients’ data (5). Similar national or regional initiatives, organized in different ways, but usually financed in part by sale of data access and intellectual property rights, are being explored in Estonia, China, Singapore, and Tonga. Specific projects addressed to certain diseases are also underway. The Danish National Birth Cohort Study of 100 000 pregnancies is mapping the DNA of mothers and their babies to probe the causes of congenital disorders and other problems. The Acute Coronary Event DNA Library Project is correlating subjects’ gene sequences with epidemiological data to understand genetic factors in premature coronary artery disease. The Avon Longitudinal Study of Parents and Children is studying the interplay between genes and environment in childhood infection, allergies, asthma, and development in 14 000 children born in 1991-2. The significance of the word “benefit” will become increasingly important in the context of population-based genetic research. The knowledge gained from research should potentially have practical benefit and researchers should act in good faith, with the interests of the profession and of the public at heart. However, is our obligation to carefully scrutinize touching societal values and potential involved benefits: do they mean financial and health gains? Being widely recognized the benefits of creating bases of genetic information to increase public health interventions, which are the fears and the potential risks involving the projects that are in the road worldwide? From long time, voices claim that DNA’s power is perhaps too considerable, and this feeling originates legitimate fears (2). A hot debate on the subject came up in media, stimulated by celebrated scientists’ voices with solid philosophical arguments on both sides. For some, the very notion that science alone holds all the secrets of our existence has even become a religion. Richard Dawkins wrote, “we are built by DNA whose purpose is to make copies of the same DNA”. Is science all we have to explain life evolution? In many other views, science gives us no reason to deny that there are some aspects of human identity falling outside the sphere of nature and hence 3

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outside the domain of science itself. This is Francis Collins and others’ view (2), when questioned: “if disease susceptibility is not deterministic, the crusade against genomic revolution is a confounding bite to the public perception of good research. In moral balance of interests, it should emerge the imperative to share our genetic information. The identification of individual predisposition to future illnesses will allow specific medical surveillance programs. But more importantly perhaps, disease susceptibility genes would shine a bright light on the molecular pathway by which they come about. The proper understanding of such pathways offers the humanity the best opportunity ever to develop specific target therapies that might successfully work”. The status and meaning of human tissue has increasingly focused our ethical, legal and sociological debates. We recognized, as a moral imperative, to share our genetic information, duties owed to: the community, to certain institutions acting in the public interest, to one’s own family, the strength of the imperative growing as we move closer to the family unit. The way to enrol ordinary healthy people with little direct interest in genetic research is a debatable subject. Two major pathways have been advocated: commodity and altruistic gift (6). In this latter perspective, gift-giving is conceived as altruistic in nature, therefore expressing a sense of solidarity, as it is assumed to benefit the greater social good. The donation of blood serves as a comparative example of this gift-giving, being accepted it represents a social indicator of the human values prevailing in society. Distinct languages of gift have been explored to foster the provision of tissues by individuals to biomedical research. Some institutions bring participants into social relationships with researchers, attempting to demonstrate that improving human health conditions is a social purpose. Whatever the strategy, since no major genetic database is likely to deliver its potential unless the public recognizes it as a common good, we must seek the public agreement on the ethical and policy issues as the way for obtaining tissue samples in research for collective benefit. Three main topics are in discussion concerning the model of conception and availability of database information: the potential invasion of privacy; the commercial exploitation of the information generated by research; the difficulty in obtaining fully informed consent from participants.

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Concerns about the relative risks of the interventions reflect a basic principle of ethics in research: “risks to the subjects must be reasonable in relation to anticipated benefits, if any, to subjects, and in relation to the importance of the knowledge that may be reasonably expected to result.”(7). One of the instruments used in order to go far in protecting the privacy interests of persons is the anonymisation of data and samples to whom they relate. The use of anonymised procedures can give response to the gathering and use of data, since the risk of harm through misuse of information is greatly reduced (7).We have to be aware that when anonymisation of data occurs, the quality of the unique relationship that individuals have with their samples or personal information is reduced, and this permits other interests to weigh move heavily in the balance (7). There is a need of developing mechanisms to avoid commercial exploitation of the collected data. The benefit of DNA databases is to provide a repository of information that can be used as a research tool, primarily to investigate the interactions between genes, environment and life style, features that are thought to be responsible for common diseases. This information can be kept for many years and used for secondary research purposes, by different researchers simultaneously. In the particular case of Iceland and Estonia access by third parties (e.g. pharmaceutical companies ) is allowed, being based on a fee, on the intention that the population collection will be self-financing (4). Objections on the utilization of genetic data in population collections rely upon the informed consent, the internationally agreed standard for biomedical research, frequently missing for the purpose. Informed consent is at the heart of ethical practice in medical research. Public participation in genetic databases can be considered both an ethical and a wider social issue. Rather than extending the notion of consent to increasingly wider groups of peoples, Sue Weldom suggests that there is a need to think in terms of different kinds of participative relationship between science and society. Individuals participate in medical research within a social context and this representation is a wider concept of engagement and another level of participation based on what has been called a “scientific citizenship” (6). An important issue deals with the use of genetic data obtained from children with their parents’ permission. There is a growing body of literature about the rights of children to influence and shape their own life worlds (10,11). Do children perceive notions of risk with regard to different types of information and how this might influence the validity of the proxy consent 5

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process? The very notion of parental rights to make decisions within a proxy consent framework is made problematic by the transitory nature of childhood when discussing the long term use of biological samples (11). Relevant conclusions were obtained from the AVON study, a longitudinal study operating in UK. The views of parents and children differ in what is personal information. Whilst individual children grow into adults, as representatives of that group, their views are important for the “rights” of future children in that particular development phase. Williamson considers that children’s views of what sensitive information is, might change over time, partially on account of development changes and cultural expectancies (9). The storing of genetic and other information and the linking of databases containing such information will, in the near future, create some of the most pressing ethical questions in medicine, requiring a balancing of ethical obligations to operate in the public interests and to respect confidentiality, on one hand, and the informed consent of individual patients and healthy persons, on the other. The ethical implications of genetic information and how it is used need to be addressed at a broader social or political level, not individuals, families and practitioners. There is a touching mission for the national Offices of Public Health: how to integrate advances in human genetics into public health research policy and programs and to defend individual rights and human dignity. In summary: the information about human differences pouring forth the science of human genetics provides us with a multitude of opportunities to treat people differently according to aspects of their genetic makeup. Deciding which uses of this information are just and which are unjust will require us to re-examine the ethical significance of a wide variety of human differences for social purposes of health policies (Thomas Murray, 1992). We all agree that all men are created equal, commitment to equality being embodied in our political tradition having roots immersed in an old cultural background. We know that people differ in their appearance, their talents and their character, among other things and those differences matter enormously. Interestingly, human genetics in contrast is a science of inequality, committed to the study of human particularities and differences (2). How to assimilate these evidences of human differences without undermining our commitment to political, legal and moral equality is a major challenge for the ethical councils.

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Genetic databases create new dimensions and new niches to examine the ethics of different traditions of research and to undertake a comparative analysis in different societies of the world and its implications on global health.

References 1.

Watson JD & Crick FH, Nature, 171:737, 1953.

2.

Collins FS, Weiss L, Hudson K, in Ethical Issues in Modern Medicine, McGraw Hill pp 553, 2003

3.

Thompson A & Chadwick R, Clinical Genetics, in Genetic Information: Acquisition, Access and Control, NY Kluwer, 1999

4.

Chadwick R & Berg K, Nature Reviews, 2: 318, 2001

5.

http://www.deCode.com (2003)

6.

Weldom S, Public consent or scientific citizenship, in Genetic Databases, Routledge, London, pp 161, 2004

7.

http://www.who.int/genomics/elsi/elsiatwho/en/index.html#gd

8.

Tutton R, Person, property and gift, in Genetic Databases, Routledge, London, pp 19, 2004

9.

http://www.bristol.ac.uk/Depts/Ethics/CEM/epeg_interim_reprt.htm (2001)

10. Neale B, Childhood, 9:455, 2002 11. Alderson P, Utopia or dystopia, in Children and Young People Enviroment, Dunedin: Children issues centre, pp 87, 2002 12. Murray TH, Hastings Law Center Report, 4: 30, 29, 1987

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