The Cambridge textbook of bioethics

154 H. L. Greenwood and A. S. Daar

It has been estimated that stem cell-based therapies, one aspect of regenerative medicine, could potentially benefit over a hundred million patients in the USA alone for conditions such as diabetes mellitus, autoimmune diseases, cardiovascular disease, cancer, and neurodegenerative diseases (Commission on Life Sciences, 2002). Though still in the early stages of development, regenerative medicine has produced several therapies currently available on the market. These include the tissueengineered skin substitute Apligraf (Petit-Zeman, 2001) and the adult stem-cell-containing bone regenerating therapy Osteocel (http://www.osiristx. com/products_osteocel.php).

Given the new therapies that regenerative medicine is likely to produce, the high level of media and public attention the field is receiving, and the experimental nature of many of the regenerative medicine therapies currently available, how should clinicians respond to patients’ inquiries and what ethical issues does this field raise?

Why is regenerative medicine important?

Ethics

Regenerative medicine raises a number of ethical issues, some of which, such as the moral status of the embryo, are relevant at the broad societal and policy levels. This section focuses specifically on ethical issues that are likely to be encountered in everyday clinical practice: informed consent, decisionmaking capacity, therapy versus enhancement, and transplantation ethics. Each of these four issues will be discussed in turn.

Firstly, regenerative medicine presents new challenges to the process of informed consent. This is partly the case because many regenerative medicine therapies are currently available only through clinical trials, and clinicians will, therefore, face the question of whether or not their patients should enroll in such trials. In these cases, extra weight is placed on the importance of proper informed consent because the potential risks associated with

such experimental therapies are largely unknown (McKneally and Daar, 2003; Kimmelman, 2005). Certain regenerative medicine therapies, such as gene therapy, are associated with a higher degree of uncertainty than traditional therapeutics because they are not backed by a long history of pharmacological data that can provide a degree of predictability (Kimmelman, 2005). It is also the case that patients, particularly severely ill patients, can inaccurately perceive the purpose of a trial as one designed to provide direct therapeutic benefit rather than to produce generalizable knowledge (Lo et al., 2005). Clinicians, therefore, must be particularly alert to their obligation to fully disclose and explain potential risks, benefits, and areas of uncertainty in order to allow their patients to give true and full informed consent to treatment.

Regenerative medicine also presents challenges to the informed consent process because of its innovative nature. As an innovative technology, regenerative medicine raises questions regarding a patient’s ability to consent fully to treatment given that the therapies are often complex and unfamiliar (Lo et al., 2005). Simplifying complex material so that patients can appropriately comprehend potential therapies can be challenging. Clinicians, however, have an ethical obligation to provide clear and reliable information to patients and to verify that the patient has fully understood this discussion (Lo et al., 2005). The duty to inform patients accurately and thoroughly is of particular relevance in the face of media attention and hype, which may lead to unrealistic expectations of potential therapeutic outcomes.

Secondly, regenerative medicine can raise issues related to a patient’s capacity to consent to treatment. This relates primarily to therapies targeted at the brain, and it takes on particular importance with respect to regenerative medicine because of the newness of the technology, the complexity of the organ being targeted, and because many of the patients receiving such therapies will be suffering from neurodegenerative diseases that could compromise their decision-making capacity (Glannon, 2006).

Thirdly, clinicians could face issues regarding the appropriate application of regenerative medicine therapies given their potential dual use; that is, given their ability to be used as a therapeutic tool but additionally as a method of enhancing normal function (Daar, 2005). Precisely what constitutes ‘‘impaired’’ versus ‘‘normal’’ function, and thus what constitutes therapy or enhancement, remains undefined and will most likely be addressed on a case-by-case basis. Carrying out an intervention purely for enhancement purposes does not necessarily mean that it is unethical (Miller and Brody, 2005). Enhancements can, however, raise concerns that concepts of normalcy may be shifted, that the autonomy of children will not be respected, and that a person’s sense of self may be affected, particularly when considering neurological enhancements (Wolpe, 2002; Sandel, 2004). One emerging neuroregenerative treatment, for instance, involves injecting self-assembling synthetic peptides into the brain, which form nanofiber scaffolds in vivo to stimulate brain tissue and nerve regrowth. This technique has been successfully used to restore sight in hamsters with severed optical nerves (Ellis-Behnke et al., 2006).

Finally, given that the application of many regenerative medicine therapies will involve the transplantation of cells, tissues, organs, or bioartificial constructs into the body, ethical issues similar to those faced by the field of traditional transplantation are raised. These issues include the ethics of procuring donor materials and compensating donors, respect for different cultural perspectives on organ transplantation, as well as protecting patient safety, particularly with respect to non-human animalderived materials (Rizvi, 1999; Abouna, 2003). Unlike traditional transplantation, where organ procurement and transplantation occur within a relatively short time frame, it may be the case that cells donated for regenerative medicine therapies are preserved and used many months or even years after the time of donation. This raises the question of whether donors should be re-contacted to update their family history in the interests of protecting the safety of the recipient. Such re-contact would,

however, need to be weighed against the donor’s right to privacy and confidentiality (Lo et al., 2005).

Law

The law relevant to regenerative medicine is primarily focused on the regulation of stem cell research. This legislation will affect the extent to which physicians will encounter regenerative medicine therapies in practice, and the kinds of therapy that are at their disposal. There is currently no international consensus on the regulation of stem cell research (Isasi et al., 2004). As such, legislation varies broadly worldwide, from permissive, to flexible, to restrictive policies (MBBNet, 2007).

Countries with permissive policies on stem cell research include China, India, and the UK (Human Fertilisation and Embryology (Research Purposes) Regulations, 2001; Greenwood et al., 2006). In these countries, stem cells may be derived from a wide variety of sources, including the derivation of human stem cells from embryos created specifically for research purposes through somatic cell nuclear transfer. Somatic cell nuclear transfer, also called therapeutic cloning, is a process in which the nucleus of an oocyte is removed and replaced with the nucleus of a somatic cell, and the oocyte is stimulated to divide. Once cell division has reached the blastocyst stage, approximately four to five days later, stem cells can be harvested from the inner cell mass of the embryo (Lanza et al., 1999).

Countries with flexible legislation limit the methods of acceptable stem cell procurement. In countries such as Canada (Assisted Human Reproduction Act, 2004) and Brazil (Biosafety Law of 2005 [Nelson, 2005]), human embryonic stem cells may be derived from unused embryos created for the purposes of in vitro fertilization given that proper consent procedures are followed. Embryos may not, however, be created specifically for research purposes using somatic cell nuclear transfer.

Countries with restrictive stem cell legislation vary widely. The USA, for instance, restricts federal funding for embryonic stem cell research to stem cell lines already in existence at the time of the

156H. L. Greenwood and A. S. Daar

Presidential announcement on stem cell research in 2001. The ban on creating new embryonic stem cell lines, however, does not apply to research funded by private or state funding. A motion to loosen federal funding restrictions on human embryonic stem cell research, the Stem Cell Research Enhancement Act of 2005, passed both the House of Representatives and the Senate but was vetoed by President George W. Bush in July 2006 (Congress of the United States of America, 2006). In Italy, by comparison, all embryonic stem cell research is banned under legislation that regulates assisted human reproduction. A June 2005 referendum to amend this legislation failed because voter turnout was below the 50% required for quorum (UK Department of Health, 2005).

Policy

Distinct from legislation enacted to define what is and what is not legal with respect to regenerative medicine, several government agencies are creating policies to guide the development and use of regenerative medicine therapies. From a policy perspective, regenerative medicine presents new challenges in regulating emerging products to ensure quality control and patient safety (Daar, 2005). The case of tissue engineered products illustrates these challenges particularly well.

Traditionally, the regulatory route of a product depends on its principal purpose or mode of action. The primary mode of action of drugs is via chemical means, while medical devices act primarily through physical means (Jefferys, 2003). Tissue-engineered products, however, often integrate these two functions. A physical scaffold serves as the framework on which cells are seeded. Growth factors stimulate the growth of the cells on the scaffold, and the scaffold itself may release soluble molecules to encourage regeneration in vivo (Koh and Atala, 2004; Sohier et al., 2006). Many countries are still striving to create policy that can accurately and effectively regulate the development and application of tissue-engineered products (Jefferys, 2003). The European Union Commission to Regulate

Tissue Engineering Technologies released draft regulations for public comment in May 2005 (European Commission, 2005). In the USA, the Food and Drug Administration (2004) has created the Office of Combination Products to coordinate the regulation of tissue engineered products. Additionally, the current Good Tissue Practices Final Rule, released in the USA in May 2005 (US Food and Drug Administration, 2005), strives to regulate celland tissue-based products by focusing primarily on safety and the potential for communicable disease transmission rather than on product identity standards (Preti, 2005).

Empirical studies

Empirical studies on the ethics of regenerative medicine largely focus on public opinions regarding the appropriateness of embryonic stem cell research and their understanding of stem cell issues (Perry, 2000). These studies may provide some guidance for clinicians regarding the beliefs they are likely to encounter when discussing regenerative medicine therapies with their patients and the level of comprehension they can expect their patients to have.

A recent study of nine countries in the European Union, for example, showed that the majority of those surveyed supported using spare embryos from in vitro fertilization for stem cell research but not embryos derived via somatic cell nuclear transfer (Solter et al., 2003). Results released in a study involving 2212 Americans showed that twothirds of respondents either approved or strongly approved of embryonic stem cell research (Hudson et al., 2005).

Public understanding of stem cell research has also been evaluated through empirical work. A study found that 60% of Americans surveyed felt that they had a ‘‘good understanding’’ of stem cellrelated issues (Nisbet, 2004). A follow-up study, however, asked Americans to identify specific kinds of stem cells that came to mind when discussing stem cell issues. More than half of the respondents replied that they did not know, and only 17% identified

embryonic stem cells (Nisbet, 2004). The Genetics and Public Policy Center in Washington DC tested public understanding of stem cell and cloning issues among Americans and revealed incomplete or incorrect knowledge among Americans regarding stem cells and cloning; 45% of the 4834 Americans surveyed believed that is was currently possible to clone a human baby (Burton, 2005).

How should I approach regenerative medicine in practice?

Regenerative medicine will present issues for a range of clinicians, including family physicians, transplant surgeons, neurologists, and other healthcare practitioners providing care to patients seeking and undergoing regenerative medicine therapies.

Clinicians faced with the question of whether they should recommend patients for clinical trials of regenerative medicine therapies should take extra care to ensure that informed consent is a top priority. Clinicians should disclose all areas of potential risk, including any cases in which unforeseen risks have occurred (Kimmelman, 2005). Any areas of uncertainty with respect to emerging therapies should be openly acknowledged. Time for in-depth discussion with patients should be allotted and should include the specific purpose of the clinical trial in order to avoid any therapeutic misconception on the part of the patient (McKneally and Daar, 2003; Kimmelman, 2005). Clinicians should also inform the patient of any standard treatments available (McKneally and Daar, 2003). Throughout this process, clinicians should be sensitive to the fact that patients seeking experimental therapy may be particularly vulnerable because of severe illness or because they have exhausted all other treatment options.

The high level of media attention around regenerative medicine may result in clinicians facing frequent requests for information from patients about specific regenerative medicine therapies. Clinicians should attempt to provide a reliable source of information independent of what their patients may have heard through the media. The complexity of

emerging treatments along with potential preconceived ideas based on media hype will require that they take extra time to engage in in-depth discussions with their patients regarding potential therapeutic options. They should attempt to explain treatment options clearly and simply, asking frequent questions of the patient to ensure full comprehension of the risks and benefits of treatment. Asking patients what they have heard regarding a particular therapy and what their expectations are will help clinicians to ascertain their level of understanding, their source of knowledge, and any assumptions and beliefs regarding regenerative medicine that they may hold.

Patients under consideration for neuroregenerative therapies should be carefully monitored to assess their capacity to consent for treatment. In cases of uncertainty, a formal decision-making capacity assessment should be undertaken. It may be the case that a substitute decision maker will be required to consent to treatment for the patient. A more detailed discussion of these issues is contained in Ch. 3.

The cases

The clinician should obtain a full explanation from the patient in the first case of what he has heard about the therapy in order to assess his preconceived assumptions and expectations regarding new blood vessel growth. She should clearly explain the nature of clinical trials, emphasizing that participation does not necessarily entail placement in the treatment group and that many trials are not testing for direct therapeutic benefit to the patient. The clinician should clearly explain the details of the trials, openly acknowledging any information of which she is unclear. Given that the treatment is experimental, the clinician should take extra time to explain in detail the risks and benefits, emphasizing that they are currently unknown and that there have been cases where gene therapy has resulted in unforeseen consequences. Throughout this discussion, the clinician should take steps to

158H. L. Greenwood and A. S. Daar

verify that the patient has fully understood the information and that he is properly informed of standard treatments available. As a final step, the clinician should refer the patient to the coordinators of the clinical trial to receive additional information and clarification.

The clinical problems of spina bifida are well known to clinicians and the potential regenerative medicine application is easy to comprehend. Literature that has already been published on the outcomes of a few patients can help to inform the clinician’s discussion with his patient. In seven patients with spina bifida aged 4 to 19 years who received tissue-engineered autologous bladders, clinical outcomes were excellent and renal function was preserved. No adverse side effects such as metabolic consequences, urinary calculi, or abnormal mucus production were noted. Upon biopsy, the engineered bladders showed adequate structural architecture and phenotype (Atala et al., 2006). Given that the results for this therapy are early and few, clinicians will have an ethical obligation to keep abreast of the current literature in order to monitor the relative risks and benefits of the procedure and to communicate these to their patients. By the time of publication of this book, there are likely to be additional studies on which clinicians can base their advice. The importance of this breakthrough and the media attention surrounding it could lead to many more patients who wish receive such therapy.

REFERENCES

Abouna, G. M. (2003). Ethical issues in organ and tissue transplantation. Exp Clin Transplant 1: 125–38.

Assisted Human Reproduction Act 2004. Ottawa: Department of Justice.

Atala, A., Bauer, S. B., Soker, S., Yoo, J. J., and Retik, A. B. (2006). Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367: 1241–6.

Attorney General of California (2004). Stem Cell Research. Funding. Bonds. State of California. Sacramento, CA: Secretary of State of California.

Burton, K. W. (2005). Cloning in America: the Genetics and Public Policy Center surveys the nation. Genewatch 18: 13–18.

Commission on Life Sciences (2002). Stem Cells and the Future of Regenerative Medicine. Washington, DC: National Academy Press.

Congress of the United States of America (2006). Stem Cell Research and Enhancement Act of 2005. Washington, DC: Library of Congress.

Cortesini, R. (2005). Stem cells, tissue engineering and organogenesis in transplantation. Transplant Immunol 15: 81–9.

Daar, A. S. (2005). Regenerative medicine: a taxonomy for addressing ethical, legal and social issues. In Ethical, Legal and Social Issues in Organ Transplantation, ed. T. Gutmann, A. S. Daar, R. A. Sells, and W. Land. Munich: PABST, pp. 368–77.

Ellis-Behnke, R. G., Liang, Y. X., You, S. W., et al. (2006). Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc Natl Acad Sci USA 103: 5054–9.

European Commission (2005). Consultation Paper: Human Tissue Engineering and Beyond: Proposal for a Community Regulatory Framework on Advanced Therapies. Brussels: European Commission, Enterprise and Industry Directorate-General.

Glannon, W. (2006). Neuroethics. Bioethics 20: 37–52. Greenwood, H. L., Thorsteinsdo´ttir, H., Perry, G., et al.

(2006). Regenerative medicine: new opportunities for developing countries. Int J Biotechnol 8: 60–77.

Haseltine, W. A. (2001). The emergence of regenerative medicine: a new field and a new society. J Regen Med 2: 17.

Haseltine, W. A. (2003). Regenerative medicine 2003: an overview. J Regen Med 4: 15–18.

Hudson, K. L., Scott, J., and Faden, R. (2005). Values in Conflict: Public Attitudes on Embryonic Stem Cell Research. Washington, DC: Genetics and Public Policy Center.

Human Fertilisation and Embryology (Research Purposes) Regulations (2001). London: The Stationery Office for the Office of Public Sector Information.

Isasi, R. M., Knoppers, B. M., Singer, P. A., and Daar, A. S. (2004). Legal and ethical approaches to stem cell and cloning research: a comparative analysis of policies in Latin America, Asia, and Africa. J Law Med Ethics 32: 626–40.

Jefferys, D. B. (2003). An overview of recent developments in the European regulation of medicine/medical device combination products. Drug Inform J 37: 39–43.

Kimmelman, J. (2005). Recent developments in gene transfer: risks and ethics. BMJ 330: 79–82.

Koh, C. J. and Atala, A. (2004). Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine. J Am Soc Nephrol 15: 1113–25.

Kuntzman, G. (2004). Stem cell gal’s miracle steps. New York Post, 29 November.

Lanza, R. P., Cibelli, J. B., and West, M. D. (1999). Prospects for the use of nuclear transfer in human transplantation. Nat Biotechnol 17: 1171–4.

Lo, B., Zettler, P., Cedars, M. I., et al. (2005). A new era in the ethics of human embryonic stem cell research. Stem Cells 23: 1454–9.

MBBNet (2007). http://mbbnet.umn.edu/scmap.html. McKneally, M. F. and Daar, A. S. (2003). Introducing new

technologies: protecting subjects of surgical innovation and research. World J Surg 27: 930–5.

Miller, F. G. and Brody, H. (2005). Enhancement technologies and professional integrity. Am J Bioethics 5: 15–17.

Mironov, V., Visconti, R. P., and Markwald, R. R. (2004). What is regenerative medicine? Emergence of applied stem cell and developmental biology. Expert Opin Biol Ther 4: 773–81.

Nelson, L. (2005). Biosafety law brings stem-cell research to Brazil. Nature 434: 128.

Nisbet, M. C. (2004). Public opinion about stem cell research and human cloning. Pub Opin Q 68: 131–54.

Perry, D. (2000). Patients’ voices: the powerful sound in the stem cell debate. Science 287: 1423.

Petit-Zeman, S. (2001). Regenerative medicine. Nat Biotechnol 19: 201–6.

Press, A. (2006). Stem cell proposal splits Missouri GOP.

New York Times, 12 March.

Preti, R. A. (2005). Bringing safe and effective cell therapies to the bedside. Nat Biotechnol 23: 801–4.

Rizvi, S. A. H. (1999). Ethical issues in transplantation.

Transplant Proc 31: 3269–70.

Sandel, M. J. (2004). The case against perfection: what’s- wrong with designer children, bionic athletes, and genetic engineering. Atlantic Month 292: 50–4, 56–60, 62.

Sohier, J., Vlugt, T. J., Cabrol, N., et al. (2006). Dual release of proteins from porous polymeric scaffolds. J Contr Release 111: 95–106.

Solter, D., Beyleveld, D., Friele, M. B., et al. (2003). Embryo Research in Pluralistic Europe. Berlin: Springer.

UK Department of Health (2005). UK Stem Cell Initiative. London: Government Printing Office (http://www. advisorybodies.doh.gov.uk/uksci/global/italy.htm).

US Food and Drug Administration (2004). Overview of the Office of Combination Products. Rockville, MD: US Food and Drug Administration (http://www.fda.gov/oc/ combination/overview.html).

US Food and Drug Administration (2005). Good Tissue Practices Final Rule. Rockville, MD: US Food and Drug Administration.

US Presidential Address (2001). Stem Cell Research. Washington, DC: Government Printing Office (http:// www.whitehouse.gov/news/releases/2001/08/20010809- 2.html).

Wagner, J. (2006). Stem cell bill could face filibuster.

Washington Post, 8 March, B06.

Wolpe, P. R. (2002). Treatment, enhancement, and the ethics of neurotherapeutics. Brain Cogn 50: 387–95.

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.

What is genetic testing and screening?

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 governmentdetermined 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).

Why is genetic testing and screening important?

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).

Ethics

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

Genetic testing and screening 161

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,

162R. Chadwick

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 (Ha¨yry 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 longterm 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.

Law

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.

Policy

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:

Genetic testing and screening 163

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).

Empirical studies

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