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PERSPECTIVES Links FURTHER INFORMATION Neisseria gonorrhoea | HIV-1 gp120 | foot-and-mouth disease virus | US Centers for Disease Control and Prevention | World Health Organization influenza surveillance programme | Influenza Sequence Database at Los Alamos National Laboratory | X-ray crystallography primer | Rosaceae | American Society for Microbiology — TIGR 2001 conference | Staphylococcus aureus genome | Intercell | The Institute for Genomic Research | Molecular Evolutionary Genetics Analysis | Phylogenetic Analysis by Maximum Likelihood | Robin Bush’s lab | Walter Fitch’s lab 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 392 Li, W.-H. & Graur, D. Fundamentals of Molecular Evolution (Sinauer Associates, Sunderland, Massachusetts, 1991). Yang, Z. H. & Bielawski, J. P. Statistical methods for detecting molecular adaptation. Trends Ecol. Evol. 15, 496–503 (2000). Smith, N. H., Maynard Smith, J. & Spratt, B. G. Sequence evolution of the porB gene of Neisseria gonorrhoeae and Neisseria meningitidis: evidence of positive Darwinian selection. Mol. Biol. Evol. 12, 363–370 (1995). Yamaguchi-Kabata, Y. & Gojobori, T. Reevaluation of amino acid variability of the human immunodeficiency virus type 1 gp120 envelope glycoprotein and prediction of new discontinuous epitopes. J. Virol. 74, 4335–4350 (2000). Bush, R. M., Fitch, W. M., Bender, C. A. & Cox, N. J. Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol. Biol. Evol. 16, 1457–1465 (1999). Hughes, A. L. & Nei, M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335, 167–170 (1988). Wang, G. L. et al. Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution. Plant Cell 10, 765–779 (1998). Meyers, B. C., Shen, K. A., Rohani, P., Gaut, B. S. & Michelmore, R. W. Receptor-like genes in the major resistance locus of lettuce are subject to divergent selection. Plant Cell 10, 1833–1846 (1998). Bishop, J. G., Dean, A. M. & Mitchell-Olds, T. Rapid evolution in plant chitinases: molecular targets of selection in plant–pathogen coevolution. Proc. Natl Acad. Sci. USA 97, 5322–5327 (2000). Lee, Y. H., Ota, T. & Vacquier, V. D. Positive selection is a general phenomenon in the evolution of abalone sperm lysin. Mol. Biol. Evol. 12, 231–238 (1995). Hellberg, M. E. & Vacquier, V. D. Rapid evolution of fertilization selectivity and lysin cDNA sequences in teguline gastropods. Mol. Biol. Evol. 16, 839–848 (1999). Yang, Z. H., Swanson, W. J. & Vacquier, V. D. Maximumlikelihood analysis of molecular adaptation in abalone sperm lysin reveals variable selective pressures among lineages and sites. Mol. Biol. Evol. 17, 1446–1455 (2000). Kresge, N., Vacquier, V. D. & Stout, C. D. Abalone lysin: the dissolving and evolving sperm protein. Bioessays 23, 95–103 (2001). Metz, E. C. & Palumbi, S. R. Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin. Mol. Biol. Evol. 13, 397–406 (1996). Vacquier, V. D., Swanson, W. J. & Lee, Y. H. Positive Darwinian selection on two homologous fertilization proteins: what is the selective pressure driving their divergence? J. Mol. Evol. 44, S15–S22 (1997). Biermann, C. H. The molecular evolution of sperm bindin in six species of sea urchins (Echinoida: Strongylocentrotidae). Mol. Biol. Evol. 15, 1761–1771 (1998). Palumbi, S. R. All males are not created equal: fertility differences depend on gamete recognition polymorphisms in sea urchins. Proc. Natl Acad. Sci. USA 96, 12632–12637 (1999). 18. Bush, R. M., Bender, C. A., Subbarao, K., Cox, N. J. & Fitch, W. M. Predicting the evolution of human influenza A. Science 286, 1921–1925 (1999). 19. Fitch, W. M., Leiter, J. M. E., Li, X. Q. & Palese, P. Positive Darwinian evolution in human influenza A viruses. Proc. Natl Acad. Sci. USA 88, 4270–4274 (1991). 20. Ina, Y. & Gojobori, T. Statistical analysis of nucleotide sequences of the hemagglutinin gene of human influenza A viruses. Proc. Natl Acad. Sci. USA 91, 8388–8392 (1994). 21. Fitch, W. M., Bush, R. M., Bender, C. A. & Cox, N. J. Long term trends in the evolution of H(3) HA1 human influenza type A. Proc. Natl Acad. Sci. USA 94, 7712–7718 (1997). 22. Suzuki, Y. & Gojobori, T. A method for detecting positive selection at single amino acid sites. Mol. Biol. Evol. 16, 1315–1328 (1999). 23. Yang, Z., Nielsen, R., Goldman, N. & Pedersen, A. M. Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155, 431–449 (2000). 24. Yang, Z. Maximum likelihood estimation on large phylogenies and analysis of adaptive evolution in human influenza virus A. J. Mol. Evol. 51, 423–432 (2000). 25. Strunnikova, N., Ray, S. C., Livingston, R. A., Rubalcaba, E. & Viscidi, R. P. Convergent evolution within the V3 loop domain of human immunodeficiency virus type 1 in association with disease progression. J. Virol. 69, 7548–7558 (1995). 26. Wichman, H. A., Badgett, M. R., Scott, L. A., Boulianne, C. M. & Bull, J. J. Different trajectories of parallel evolution during viral adaptation. Science 285, 422–424 (1999). 27. Wichman, H. A., Scott, L. A., Yarber, C. D. & Bull, J. J. Experimental evolution recapitulates natural evolution. Phil. Trans. R. Soc. Lond. B 355, 1677–1684 (2000). 28. Bush, R. M., Smith, C. B., Cox, N. J. & Fitch, W. M. Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution. Proc. Natl Acad. Sci. USA 97, 6974–6980 (2000). 29. Bush, R. M., Fitch, W. M., Smith, C. B. & Cox, N. J. in 30. 31. 32. 33. 34. 35. 36. 37. Options for the Control of Influenza IV (ed. Osterhaus, A. D. M. E.) (Elsevier, Amsterdam, in the press). Felsenstein, J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39, 783–791 (1985). Sullivan, N. et al. CD4-induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization. J. Virol. 72, 4694–4703 (1998). Martínez, M. A., Verdaguer, N., Mateu, M. G. & Domingo, E. Evolution subverting essentiality: dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged footand-mouth disease virus. Proc. Natl Acad. Sci. USA 94, 6798–6802 (1997). Martín, M. J., Núñez, J. I., Sobrino, F. & Dopazo, J. A procedure for detecting selection in highly variable viral genomes: evidence of positive selection in antigenic regions of capsid protein VP1 of foot-and-mouth disease virus. J. Virol. Methods 74, 215–221 (1998). Ishimizu, T. et al. Identification of regions in which positive selection may operate in S-RNase of Rosaceae: implication for S-allele-specific recognition sites in SRNase. FEBS Lett. 440, 337–342 (1998). Nei, M. & Gojobori, T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol. Biol. Evol. 3, 418–426 (1986). Nielsen, R. & Yang, Z. Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148, 929–936 (1998). Nei, M. & Kumar, S. Molecular Evolution and Phylogenetics (Oxford Univ. Press, Oxford and New York, 2000). Acknowledgements I thank N. Cox, C. Bender Smith and W. Fitch for their contributions to our collaborative work on influenza. I am supported by a grant from the US National Institutes of Health and by funds provided by the University of California for the conduct of discretionary research by Los Alamos National Laboratory, conducted under the auspices of the US Department of Energy. OPINION Protecting genetic privacy Patricia A. Roche and George J. Annas This article outlines the arguments for and against new rules to protect genetic privacy. We explain why genetic information is different to other sensitive medical information, why researchers and biotechnology companies have opposed new rules to protect genetic privacy (and favour anti-discrimination laws instead), and discuss what can be done to protect privacy in relation to genetic-sequence information and to DNA samples themselves. The simultaneous publication of two versions of the human genome could be an important impetus to take more seriously the legal, ethical and social policy issues at stake in human genome research1,2. There are many such issues, and the one that has caused the most public concern is that of genetic privacy. As DNA sequences become understood as information, and as this information becomes easi- | MAY 2001 | VOLUME 2 er to use in digitized form, public concerns about internet and e-commerce privacy (regarding the security with which an individual’s private details are protected) will merge with concerns about medical record privacy and genetic privacy. In this paper, we outline the key public policy issues at stake in the genetic privacy debate by reviewing generally medical privacy, by asking whether genetic information is like other medical information, and by outlining the current controversies over privacy in genetic research. We conclude with some public policy recommendations. Privacy Privacy is a complex concept that involves several different but overlapping personal interests. It encompasses informational privacy (having control over highly personal information about ourselves), relational privacy (determining with whom we have personal, intimate relationships), privacy in decision- www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd PERSPECTIVES making (freedom from the surveillance and influence of others when making personal decisions), and the right to exclude others from our personal things and places. In the United States, no single law protects all of these interests, and privacy law refers to the aggregate of privacy protections found in constitutions, statutes, regulations and common law3–9. Together, these laws reflect the value that US citizens place on individual privacy, sometimes referred to as “the right to be left alone” and the right to be free from outside intrusion, not as an end in itself, but as a means of enhancing individual freedom in various aspects of our lives. The centrality of individual freedom in Western societies is evident in the United States in state laws that establish a patient’s right to make informed choices about treatment, that place an obligation on physicians to maintain patient confidentiality and that regulate the maintenance of medical records. Privacy laws in the United States are fragmented because of the many sources of law, which includes the federal government and all 50 states. Legislative enactments are also often the result of negotiated agreements among segments of a diverse and often polarized society, rather than of a real consensus. This is perhaps most readily seen in the rules that govern highly sensitive and personal data in the United States. Unlike the approach of the European Data Protection Directive, which establishes similar rights and duties relative to different kinds of personal data (health and finance)10, the United States has different rights and duties for personal information depending on the kind of information involved. Even for medical records, there are different rules that apply to the different types of information that they contain. For example, the United States has laws that govern generally medical record information 11, as well as separate laws that govern specific types of medical information, such as HIV status12, substance-abuse treatment information13 and mental health information14. New federal regulations apply the same privacy rules to all medical information except psychotherapy records9. Such exceptionalism has been criticized, and the primary argument against specific laws that are designed to protect genetic information is that such ‘genetic exceptionalism’ would perpetuate the misconception that genetic information is uniquely private and sensitive15. Genetic privacy Is DNA-sequence information uniquely private or just like other sensitive information in an individual’s medical record? If it is not “DNA has also been culturally endowed with a power and significance exceeding that of other medical information … genetic information can radically change the way people view themselves … as well as the way that others view them.” unique, existing medical record confidentiality laws should be sufficient to protect geneticsequence information, and no new laws would be needed. Those who support genetic exceptionalism (as we do) emphasize the distinguishing features of DNA-sequence information. The DNA molecule itself is a source of medical information and, like a personal medical record, it can be stored and accessed without the need to return to the person from whom the DNA was collected for permission. But DNA-sequence information contains information beyond an individual’s medical history and current health status. DNA also contains information about an individual’s future health risks, and in this sense is analogous to a coded ‘future diary’16. As the code is broken, DNA reveals information about an individual’s probable risks of suffering from specific conditions in the future. Our current obsession with genetic-sequence information means that it is likely to be taken more seriously than other information in a medical record that could also predict future risks, like high blood pressure or cholesterol levels. Information about the presence of proteins that specific genes might encode is also different from DNA-sequence information because the presence of certain proteins might change with time, and their levels, like cholesterol readings, can only be determined by retesting the patient personally. So, proteomics will not require new privacy rules, but rather the enforcement of existing privacy rules for medical records. DNA-sequence information might also contain information about behavioural traits that are unrelated to health status, although scepticism is called for in this area17. Our use of the ‘future diary’ metaphor has been criticized as potentially perpetuating a mistaken view of genes as deterministic15. We understand this criticism, and also reject the idea that genes alone determine our future. Nevertheless, we continue to believe the NATURE REVIEWS | GENETICS future diary metaphor best conveys the private nature of genetic information itself. Our future medical status is not determined solely by genetics, any more than our past diaries are the only source for accurate information about our past (or even necessarily reflect it). DNA information, like a diary, however, is a uniquely private part of ourselves. An individual’s DNA can also reveal information about risks and traits that are shared with genetic relatives, and has been used to prove paternity and other relationships18. An individual’s DNA has the paradoxical quality of being unique to that individual yet shared with others. Even if one believes that the DNA-sequence information extracted from an individual’s DNA is no more sensitive than other medical information, this says nothing about the need to protect the DNA molecule itself. In this regard, we think it is useful to view the DNA molecule as a medical record in its own right. Having a DNA sample from an individual is like having medical information about the individual stored on a computer disk, except in this case the information is stored as blood or as other tissue samples. Like the computer disk, the DNA sequence can be ‘read’ by the application of technology. So, regardless of the rules developed to control the use of genetic information when it is recorded in traditional paper and electronic medical records, separate rules are also needed to regulate the collection, analysis, storage and release of DNA samples themselves. This is because once a physician or researcher has a DNA sample, there is no practical need for further contact with the individual from whom the DNA was obtained, and DNA tests could be done on the stored sample (and thus on the individual) in their absence. Some of these tests might as yet be undeveloped but all will produce new genetic information about the individual. DNA has also been culturally endowed with a power and significance exceeding that of other medical information19. Much of this significance is undoubtedly misplaced, but can be justified in so far as genetic information can radically change the way people view themselves and family members, as well as the way that others view them. The history of genetic testing, particularly in relation to rare monogenic diseases, such as Huntington disease, provides us with examples of this impact. Studies of individuals who have undergone testing in clinical settings show the changes in self-perception caused by positive, as well as negative, test results20,21. Individuals with a decreased risk of having a genetic disease have reported difficulty in setting expectations for their personal and VOLUME 2 | MAY 2001 | 3 9 3 © 2001 Macmillan Magazines Ltd PERSPECTIVES Box 1 | Enterprises that raise challenging issues • deCODE Genetics plans to computerize the patient records of the national health service of Iceland, and collect DNA samples from members of the population for genetic linkage analysis and association studies on common diseases. Results will be cross-referenced with information from publicly available genealogical information. Subscriptions to these databases are sold to researchers and information is entered into them on the basis of presumed consent. • The UK Population Biomedical Collection, a joint initiative of the Medical Research Council and the Wellcome Trust, plans to focus on understanding the interactions between genes, environment and lifestyles in cancer and cardiovascular conditions. Their goal is to collect samples of up to 500,000 people and link these samples to an ongoing collection of the individuals’ medical data. Investigators may be granted access to the results of genotyping, but not to the DNA samples. • Ardais Corporation, a start-up biotechnology company that intends to enter into agreements with several major hospitals in the United States under which surgical patients will be asked for tissue that is left over from operations. These samples will be linked to records that detail the patient’s medical history and family information. Tissue libraries and data will be licensed to researchers. • Autogen Ltd, an Australian biotechnology firm that has secured exclusive rights to collect tissue samples and health data from the population of Tonga. The firm hopes to identify new diseaserelated genes and to aid the development of new drugs to prevent or treat common diseases, such as diabetes. It has pledged to abide by stringent ethical standards, to collect samples and data from individuals who voluntarily participate and to make the health database available to the Tongan people. professional lives in a more open-ended future. Adjustments seem to have been particularly difficult for those who have already made reproductive decisions based on the presumption that they were at high risk for developing a disease20. Consequently, it is good policy to provide genetic counselling before and after testing. And in the interests of protecting the privacy of children and adolescents, some institutions have also adopted a policy of refusing parental requests to test children for late-onset diseases when no medical intervention is available to prevent or alleviate the genetic condition22. Perhaps the principal reason why neither DNA-sequence information nor DNA samples themselves have been afforded special privacy protection is the strongly held view of many genetic researchers and biotechnology companies that privacy protections would interfere with their work. One court in the United States has addressed whether constitutional rights to privacy are implicated by genetic testing. In Norman-Bloodsaw v. Lawrence Berkeley Laboratory, employees of a research facility owned and operated by state and federal agencies alleged that non-consensual genetic testing by their employers violated their rights to privacy. Holding that the right to privacy protects against the collection of information by illicit means, as well as unauthorized disclosures to third parties, the court stated “One can think of few subject areas more personal and more likely to implicate privacy interests than that of one’s health or genetic make-up”23. 394 DNA research and privacy Now that the human genome has been sequenced, attention is shifting to research on genetic variation that is designed to locate genes and gene sequences with disease-producing or disease-prevention properties24. Some researchers have already taken steps to form partnerships and create large DNA banks that will furnish the material for this research25,26.Others want to take advantage of the large number of stored tissue samples that already exist27. In the United States, for example, the DNA of about 20 million people is collected and stored each year in tissue collections ranging from fewer than 200 to more than 92 million samples28.Collections include Guthrie cards, on which blood from newborns has been collected for phenylketonuria screening since the 1960s, paraffin blocks used by pathologists to store specimens, blood-bank samples, forensic specimens and the US military’s bank of samples for use in identifying bodily remains28. Several factors have contributed to the proliferation of DNA banking: the relative ease with which DNA can be collected, its coincidental presence in bodily specimens collected for other reasons and its immutability. Regardless of the original purposes for storing specimens, however, as the ability to extract information from DNA increases and the focus of research shifts to genetic factors that contribute to human diseases and behaviours, repositories that contain the DNA of sizeable populations can be ‘gold mines’ of genetic information. So, it is not surprising | MAY 2001 | VOLUME 2 that there is considerable interest on the part of biomedical researchers, companies that market genomic data and the pharmaceutical industry, to stake claims on these informational resources29 and to exploit them for their own purposes. Commercial enterprises, as well as academic researchers, have equally strong interests in making it relatively easy to access DNA samples that can be linked to medical records for research purposes. Representatives of these constituencies have been vocal in arguing that requirements for informed consent and the right to withdraw data from ongoing research projects (two aspects of genetic privacy) would greatly hamper their research efforts30. When US federal rules apply to such research — as is the case with federally funded projects and any projects related to obtaining approval from the US Food and Drug Administration to market drugs or devices — the local Institutional Review Board (IRB) must approve the research protocol. These boards should not waive basic federal research requirements on informed consent (nor exempt researchers from them) except when the IRB determines that the research will be conducted in such a way that the subjects cannot be personally identified31. If existing research rules were consistently and diligently applied perhaps we could confidently state that the privacy of research subjects is adequately protected32. Today, however, such confidence would be misplaced32. These privacy and consent issues are not limited to the United States (BOX 1). The most internationally discussed DNA-based project has been deCODE Genetics in Iceland, a commercial project that has been opposed by the Iceland Medical Association, among others, for ‘ethical shortcuts’, such as ‘opt-out’ provisions that presume an individual’s consent (see below)33–35. The deCODE project, which has been endorsed by two acts of the Iceland parliament, involves the creation of two new databases: the first containing the medical records of all Iceland citizens, and the second containing DNA samples from them (a third database, of genealogical records, already exists). deCODE intends to use these three databases in various combinations to identify genetic variations that could be of pharmaceutical interest. The chief ethical issues raised by this project are: first, the question of informed consent for inclusion of personal medical information in the database, which is at present included under the concept of presumed consent — this requires individuals to actively opt out of the research if they do not want their information in the database; second, informed www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd PERSPECTIVES Box 2 | Assessing genetic privacy Laws or policies that purport to protect genetic privacy, at a minimum, should do the following: • Recognize individual genetic rights, particularly: • the right to determine if and when their identifiable DNA samples are collected, stored or analysed; • the right to determine who has access to their identifiable DNA samples; • the right of access to their own genetic information; • the right to determine who has access to their genetic information; • the right to all information necessary for informed decision-making about the collection, storage and analysis of their DNA samples and the disclosure of their private genetic information. • Limit parental rights to authorize the collection, storage, or analysis of a child’s identifiable DNA sample so as to preserve the child’s future autonomy and genetic privacy. • Prohibit unauthorized uses of individually identifiable DNA samples, except for some uses in solving crimes, determining paternity or identifying bodily remains. • Prohibit disclosures of genetic information without the individual’s explicit authorization. • Strictly enforce laws and institutional policies. • Provide accessible remedies for individuals whose rights are violated. • Institute sufficient penalties to deter and punish violations. consent for the inclusion of DNA in the DNA databank in an identifiable manner (whether encrypted or not, and no matter which entity holds the encryption key); and third, whether the right to withdraw from the research (including the right to withdraw both the DNA sample itself from the databank and all information generated about it) can be effectively exercised. Other issues include the security of the databases and community benefit from the research project itself35. Iceland is providing a type of ethical laboratory that will help identify the key issues involved in population-based genetic research, and might help to highlight why international privacy rules are desirable. Although Icelanders themselves do not seem overly concerned with the adequacy of deCODE’s plans to protect their personal privacy, other countries have not been as disposed to giving away the autonomy and privacy of their citizens so readily. Both Estonia and the United Kingdom, for example, have announced that their population-based DNA collections and research projects will contain strong consent and privacy-protection provisions36,37. The privacy problems inherent in large population-based projects could be avoided altogether by stripping DNA samples of their identifiers in a way that makes it impossible to link personal medical information with DNA samples (at least by using standard identifying methods). Of course, most researchers want to retain identifiers to do follow-up work or confirm diagnoses38. Such identification retention, however, puts individuals at risk of breach of confidentiality and invasion of privacy, and these risks are why both informed consent and strong privacy-protection protocols are ethically necessary for genetic research38. These considerations also apply to criminal DNA databases as even convicted felons have privacy rights. Risks of disclosure of personal genetic information are so high that some prominent genetic researchers, including Francis Collins and Craig Venter, have suggested concentrating not on privacy rules, but rather on anti-discrimination legislation that is designed to protect individuals when their genetic information is disclosed, and when insurance companies, employers or others want to use that information against them39. We agree that anti-discrimination legislation is desirable, but it does not substitute for privacy rules that can prevent the genetic information from being generated in the first place without the individual’s informed authorization. This point is well illustrated by a law recently enacted in Massachusetts — a state with a population more than 20 times larger than the population of Iceland40 — that has been mistakenly characterized in the US press as ‘a sweeping set of genetic privacy protections’41. Under this new law, written informed consent is a prerequisite to predictive (but not diagnostic) genetic testing and to disclosing the results of such tests by entities and practitioners that provide health care. The law also limits the uses that insurers and employers can make of genetic information. However, it places no limitations on how researchers and biotechnology companies that engage in projects requiring the use of identifiable samples and identifiable genetic information conduct NATURE REVIEWS | GENETICS their activities. Apparently, those who drafted the statute believed that they need not be concerned about protecting research subjects because research with human subjects is regulated by the federal government, failing to recognize that many activities of genomic companies do not fall under the jurisdiction of the federal regulations. Policy recommendations We have argued in the past that a principal step to achieving genetic privacy would be the passage of a comprehensive federal genetic privacy law42,43. The primary purpose of such a law is to give individuals control over their identifiable DNA samples and the geneticsequence information extracted from them. The model we suggest provides that individuals have a property interest in their own DNA — and that this property interest gives them control over it. Control could also, however, be obtained by requiring explicit authorization for the collection and use of DNA, including its research and commercial use. We believe that in the absence of authorization no one should know more about an individual’s genetic make-up than that individual chooses to know themselves, and that an individual should also know who else knows (or will know) their private genetic information (see BOX 2). Current US state laws at best offer some economic protections and a patchwork of genetic privacy protections. But existing state laws have significant gaps and inconsistently regulate those who engage in DNA banking and genetic research. Nevertheless, existing privacy laws provide models and a foundation that can be built on to protect genetic privacy and empower individuals in this genomic era. But until comprehensive federal legislation is passed in the United States, US citizens will have to rely on those who create and maintain DNA banks to design, implement and enforce self-imposed rules to protect individuals. One proposal to deal with privacy issues and individual control over genetic information is to have DNA samples and medical records collected by a ‘third-party broker’ of genetic information who would then, with the informed consent of the individual, make this information available to researchers in a coded form. A for-profit company, First Genetic Trust, has been formed in the United States to try out this model44. Individuals are solicited through the internet to participate in the Trust and all communication with those who participate, including consent to new studies, will take place over the internet. The purpose of the Trust is to assure individuals that no one would be able to use their DNA, or their personal VOLUME 2 | MAY 2001 | 3 9 5 © 2001 Macmillan Magazines Ltd PERSPECTIVES medical information associated with it, without the individual’s authorization. Some might criticize this approach as going too far in protecting participants, noting that consent is not generally necessary for IRB-approved research that does not involve identifiable data. Regardless of the fact that First Genetic Trust itself will not be engaged in research, as long as data held by the Trust can be linked to individuals, we think authorization should be required and that proposals such as this one are a step in the right direction. Whether arrangements such as these will lead to significant public participation in genetic research remains to be seen. Despite the availability of tests for genes that predispose individuals to several diseases, including Huntington disease and some forms of breast and colon cancers, the number of people who choose to undergo clinical genetic testing has fallen far below the expectations of the companies that sell tests and of the physicians who believe their patients would benefit from them45. Why is the public, which is on the one hand fascinated with each advance in mapping the genome, the identification of particular genes and the possible association of a gene with particular human characteristics, simultaneously reticent to undergo genetic testing? Explanations that individuals give for avoiding genetic tests include fear of discrimination, concern over the impact on family members, lack of effective treatments and preference for uncertainty about the future46,47. Privacy protections have little, if any, impact on attitudes towards the future. Nevertheless, by regulating the creation, maintenance and disclosure of information, they can reduce privacy risks and provide some reassurance to those who might not otherwise participate in genetic research or clinical testing. Once individual interests in privacy and in being treated fairly on the basis of genetic information have been addressed, only property issues remain. Individuals can be thought of as having a property right in their DNA, including, among other things, the right to restrict others from ‘trespassing’ on their property without permission42. One US state, Oregon, incorporated an individual’s right of ownership of DNA into its laws in 1995 (REF. 48). Objections that this law would inhibit research in that state echoed objections that researchers and industry have made elsewhere to explicit and strict privacy rules49,50. Acknowledging property interests in DNA need not impede research any more than respect for individual privacy would. Conversely, individuals are free to grant property rights in their DNA to researchers, 396 and are much more likely to do so if their privacy can be guaranteed (as it can be if identifiers are not retained). DNA can rightly be seen as containing uniquely personal, powerful and sensitive information about individuals and their families. Some individuals want to know as much of this information about themselves as possible, and might be willing to share this information with their families and others. Others would rather remain ignorant about their own genetic make-up, and thus their risks for future illnesses, or at least to keep others ignorant of such information. We believe that individual choices are best served by policies that place primary control over an individual’s DNA and genetic information in the hands of individuals. We also believe privacy protections will prove as necessary for the future of genetic research and clinical applications as they will be for the future of e-commerce. We believe that the sooner that reasonable genetic privacy protections are in place, the better it will be for all of us. Patricia A. Roche and George J. Annas are at the Health Law Department, Boston University School of Public Health, 715 Albany Street, Boston, Massachusetts 02118, USA. 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