governing population genomics: law, bioethics, and

Netter have made both the cellular telephone and the Internet more secure. Laws have been passed to prevent unauthorized interception of telephone calls and email.'Zo The UHID should be approached in the same spirit. It, too, is a new technology.The systemenvisioned here is characterized by its multi-tiered nature. The first level of recommended identification is biometric in nature. The biometric identifier is linked to an alphanumeric identifier maintained in a centralized database. In turn, that number, or a variant of it, is linked to two separate databases, one that contains only a patient's medical information, and another that contains only the patient's personally identifiable information. In this way, the UHID allows for a central database of anonymous patient information to be created. In addition to this use of technology to protect personally identifiable information from unauthorized access, the law also should be structured to protect against consequences of any breach of privacy. For instance, apatient shouldnot suffer insurance or employment penalties due to unauthorized disclosures of information. The Privacy Rule of 2001 should be amended to better protect Americans' personal medical information. Consent requirements should be augmentedso that a patient can provide medical information without fear that it will be shared with unauthorized private parties. The government should be required to obtain a search warrant before acquiring medical records without patient consent, with the possible exception of true national emergency situations. With these protections, a voluntary UHID has the capacity to greatly improve patient care and the efficiency of the overall system. Patients can weigh any remaining privacy concerns against the benefits they stand to gain from opting-in to this new system.

GOVERNING POPULATION GENOMICS: LAW, BIOETHICS, AND BIOPOLITICS IN THREE CASE STUDIES David E. Winickoff' ABSTRACT: Existing scholarship on population genomics has only superficially addressed issues of power and political process. Accordingly, questions of politics and governance pervade the analysis ofthree population genomics case studies that follow: the Human Genome Diversity Project, Iceland's Health Sector Database, and "Clinical Genomics" as defined by the Beth Israel-Ardais collaboration. An examination of these case studies reveals that the common law, U.S. regulatory law, and international law have not developed the political sophistication to make the traditional promises of biomedical ethics-respect for autonomy, justice, and beneficence--come to fruition. Further, comparisonsofthese projects illuminate three areas ripe for reframing-informed consent, expert ethical oversight, and commercial benefits. Four avenues of reform are suggested. CITATION: David E. Winickoff, GoverningPopulation Genomics: Law, Bioethics, and Biopolitics in Three Case Studies, 43 Jurimetrics J. 187-228 (2003). Increasingly, knowledge about the genome is becoming an element in the relation between individuals and institutions, generally adding to the power of institutions over individuals. -Richard Lewontin, Alexander Agassiz Research Professor of Zoology, Harvard university1

120. E.g , Electronic Communications Privacy Act, 18 U.S.C. $$ 2701-1 1 (2000).

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'David E. Winickoff is a Post-Doctoral Fellow at the Kennedy School of Government, Harvard University, in the Program on Science, Technology, and Society. The author thanks Heather Butterfield, Joseph William Singer, Sheila Jasanoff, Susan and Richard Winickoff, and Peter Hutt for their assistance. 1. RICHARD LEWONTIN, IT AIN'T NECESSARILY SO: THEDREAM01:THE HUMANGENOME AND OTHERILLUSIONS 166 (2d ed. 2001).

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Protecting the rights and values of volunteers in biomedical research has been a major concern since abuses of research subjects in the United States came to light in the 1960s and 1970s.' These unethical research practices demonstrated a need to develop clearer and more systemic protections of human research subjects. As a result, bioethicists articulated respect for persons, justice, and beneficence as the "basic ethical principles,"3 with informed consent and the Institutional Review Board (IRB) as the mechanisms for implementing them.4 This protection regime was aimed both at preventing potentially unwanted physical impacts of biomedical research, and at restoring the trust that is crucial for medical advance.' Since the 1970s two major developments have introduced complications into this system of protection. First, decisions by the Supreme Court and Congress in the 1980s significantly increased the potential for commercial development of As a result of this change, commercial interest has biomedical di~coveries.~ become a major force driving biomedical research at universities, govenunent agencies, and hospitals.' As a result, academic medical centers and other health

2. For a history of federal regulation in this area, see, for example, RUTHR. FADEN& TOM L.

BEAUCHAMP, A HISTORYAND THEORY OF INFORMED CONSENT 15 1-232 (1986); NAT'LBIOETHICS ,&DVISORY COMM'N, ETHICAL AND POLICY ISSUES M RESEARCHINVOLVING HUMAN PARTICIPANTS (2001) [hereinafter NBAC]. supra note 2, at 2 15-17. For an overview of these principles, see, for 3. FADEN& BEAUCHAMP, & JAMESF. CHILDRESS, PIUNCIPLESOF BIOMEDICAL ETHICS(5th ed. example, TOML. BEAUCHAMP 2001). supra note 2, at 200-32. 4. See FADEN& BEAUCHAMP, 5. JESSICABERGETAL., INFORMEDCONSENT: LEGALTHEORY A N D C L ~ N ~ C A L P R A C T ~2C4E 9 4 1 (2d ed. 2001). 6. Over the last 20 years, courts expanded the scope of intellectual property rights. See, e.g., Diamond v. Chakrabarty, 447 U.S. 303 (1980) (holding that modified life forms could be patented, paving the way for amajor expansion ofbioengineeringpatents); Moore v. Regents ofthe University of California, 793 P.2d 479, 493-97 (Cal. 1990) (denying a research participant property rights in his own donated cells despite recognizing the right ofresearchers to patent a line ofcells derived from the plaintiffs tissue). See also JAMESBOYLE,SHAMANS, SOFTWARE,AND SPLEENS: LAWAND THE CONSTRUCTION OF THE INFORMATION SOCIETY (1 996); Sheila Jasanoff, Ordering Life: Law and the Normalization of Biotechnology, 62 POLITEIA34 (2001). Courts and policymakers in the United States have constructed a patent system that fosters the convergence of academic genetics research, capital investment, and the biotechnology industry. See, e.g.. Rebecca S. Eisenberg, Public Research and Private Development: Patents and Technology Transfer in Government-Sponsored Research, 82 VA.L. REV. 1663 (1996) (demonstrating how congressional policy towards intellectual property rights in government-sponsored research has fostered the biotechnology industry and realigned institutional relationships). For example, in 1980 Congress passed two laws that enhanced the patent system: the Stevenson-Wydlcr Technology Innovation Act, IS U.S.C. 55 3701-3717 (2000) (making technology transfer an integral part of the research and development responsibilities of federal laboratories and employees), and the Bayh-Dole Act, 35 U.S.C. $8 200-21 I, 301-307 (2000) (encouraging small businesses and nonprofits to patent government-funded discoveries). supra note 1, at 179-83; Joseph B. Martin & Dennis L. Kasper, In 7. See, e.g., LEWONTIN, Whose Best Interest? Breaching the Academic-Induslrial Wall,343 NEWENG.J. MED. 1646 (2000); Siddhartha Mukherjee, Why Public Science Can 'IReally Be Public, NEWREPUBLIC, May 8,2000, at 14.

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care institutions have become more entrepreneurial, thus intensifying potential individual and institutional conflicts of interest.' Second, new genetic technologies have greatly enhanced the informational power of human tissue, transforming it into a commodity and an object of p r i ~ a c y .By ~ facilitating the identification and mass replication of precise segments of DNA in a short amount of time, Polymerase Chain Reaction (PCR) and other technologies have enhanced the potential of molecular biology to extract genetic information from blood, semen, hair, skin, and other tissue.'' DNA from such samples can be examined for particular genetic mutations, greatly aiding the discovery of the genetic bases of human diseases." But this same DNA could also create a genetic profile that could be used to discriminate.12 These technologies are prompting industry to seek large collections of human tissue samples for the purposes of applying "bioinformatics" to genomics research.13 "Bioinformatics" describes a biological information processing system--comprising computers, databases, on-line networking, and specialized software-that has given birth to a new research paradigm in which genotypic and phenotypic information is "mined" to identify genes, to model protein structure, and to discover drug targets.I4The bioinformatics approach requires the computer analysis of huge amounts of "bioinfonnation," that is, phenotypic information drawn from medical records and genotypic information drawn from tissue samples. Consequently, large collections of human biological samples and medical records have become a marketable commodity.

8. Robert P. Kelch, Maintaining the Public Trust in Clinical Research, 346 NEW ENG.J. MED. 285,285 (2002). 9. Human tissue as material has also become big business in America. Regeneration Technologies Inc., RTI, generated $73 million in revenues in 1999 by processing a third ofthe human tissue donated in the United States, turning body parts into products for surgery and other medical procedures. The company acquires tissue by purchasing nonprofit tissuebanks. See Ronald Campbell COUNTY REG.,May 7, 2000, at Al. et al., Anatomy of an IPO: Making Charity Pay, ORANGE 10. See, e.g., Catherine Waldby, Code Unknown: Htstories ofthe Gene, 31 Soc. STUD.SCI. 779, 785 (2001) ("Genetics today is without doubt a bioinformatic practice, characterized by a distinctive set of analytic technologies-DNA chips, PCR, searchable databases-that mediate and translate between in vivo and in silico forms of information . . . ."); NAT'LBlOETHlCS ADVISORY COMM'N, RESEARCH ~ N V O L V ~ N GHUMANBIOLOGICAL MATERIALS: ETHICAL ISSUES AND POLICY GUIDANCE 1 (1 999) [hereinafter BIOLOGICAL MATERIALS]. 11. Jeffrey R. Gulcher & Khri Stefhnsson, The Icelandic Healthcare Database and Informed Consent, 342 NEW ENG.J. MED. 1827, 1827 (2000). 12. See, e.g.,George J . Annas, Privacy Rules for DNA Databanks: Protecting Coded "Future Diaries. " 270 JAMA 2346,2346-50 (1993). 13. Genomics is the study of genomes-the totality of organisms' genetic codes-and includes genome mapping, gene sequencing, and the investigation of gene function. See Alan E. Guttmacher & Francis S. Collins, Genomic Medicine-A Primer, 347 NEWENG.J. MED. IS 12, 15 12 (2002). INFORMA14. See Dick Holdsworth, The Ethics of 2lst Century Bioinformatics, in GENETIC T~ON:ACQU~S~ON,ACCESS,ANDCONTROL 85 (Alison K. Thompson & Ruth F. Chadwick eds., 1999) [hereinafter GENETICINFORMATION].

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Many new issues emerge from the realignments of traditional markets and bodily domains brought about by the commodification of biological informati~n.'~ At the same time, public trust in biomedical research has decreased.I6 Due to bioinformation's increasing economic and social power and its intimate connection with the bodies and identities of donors, bioethicists are calling for clearer standards in the collection and use of biological samples, modifications in the regulatory regime, and greater protection for genetic privacy.17 This article attempts to fill a gap in existing scholarship on population genomics. Bioethics policy debates have only superficially addressed issues of power and political process. Perhaps too readily, bioethicists allow the standard perception of bioethics as an expert realm to obscure its political dimensions.ls The failure to address issues such as bargaining power, political representation, and resource allocation only contributes to fears that the development of biotechnology is determined by technocratic values to the exclusion of political and ethical discourse.19 These questions of power and governance are central to the analysis of three population genomics case studies that follow: the Human Genome Diversity Project, Iceland's Health Sector Database, and "Clinical Genomics" as defined by the Beth Israel-Ardais collaboration. An examination of these case studies reveals that the common law, U.S. regulatory law, and international law have not developed the political sophistication to allow the traditional promises of biomedical ethics-respect for autonomy, justice, and beneficence-to be

15. HILARYROSE, THECOMMODIFICATION OF BIOINFORMATION: THEICELANDIC HEALTH SECTORDATABASE (The Wellcome Trust, 2001). available at MANNVERND web site, the Association of Icelanders for Ethics in Science and Medicine, at http://www.mannvernd.is/greinar/ hilaryrosel-3975.pdf; Gisli Palsson & Paul Rabinow, The Icelandrc Genome Debate, 19 TRENDS IN BIOTECHNOLOGY 166 (2001). 16. Kelch, supra note 8, at 285. 17. See, e.g., Ellen Wright Clayton et al., Informed Consentfor Genetic Research on Stored Tissue Samples, 274 JAMA 1786 (1995);STORED TISSUESAMPLES: ETHICAL, LEGAL, AND PUBLIC POLICY IMPLICATIONS (Robert F. Weir ed., 1998) [hereinafter STORED TISSUESAMPLES]; Henry T. Greely, Breaking the Stalemate: A Prospective Regulatory Frameworkfor Unforeseen Research Uses of Human Tissue Samples and Health Information, 34 WAKEFORESTL. REV. 737 (1999); BIOLOGICALMATERIALS, supra note 10. 18. Scholars in the field of Science and Technology Studies (STS) have demonstrated how technical discourses tend to promote the authority of experts and hide value-laden and politically contested dimensions of policymaking. See, e.g,,ULRICHBECK, RISK SOCIETY: TOWARDS A NEW MODERNITY (M. Ritter trans., 1992);LANGDON WINNER,THEWHALEANDTHEREACTOR:ASEARCH FOR LIMITSIN AN AGEOFHIGHTECHNOLOGY 138-54 (1986);Sheila Jasanoff,Science, Politics, and the Renegotiation of Expertise at EPA, 7 OSIRIS 195 (1992).The increasing formalizationof ethics protocols in biomedical research, and the technical knowledge implicated by the research, also tends to devoliticize decisionmakinn. 19. Bruce Bimber, Three Faces of TechnologicalDeterminism,in DOESTECHNOLOGY DRIVE HISTORY: THEDILEMMA OF TECHNOLOGICALDETERMINISM 79 [Meritt Roe Smith & Leo Marx eds., 1994) (noting that technology may tend to be considered autonomous and deterministic when the norms by which it is advanced are removed from political and ethical discussion); see J ~ R G E N HABERMAS, TOWARD A RATIONAL SOCIETY 5 8 4 0 , 81-127 (Jeremy J. Shapiro trans., 1970).

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realized. Further, comparisons of the three projects illuminate three areas ripe for reframing-informed consent, expert ethical oversight, and commercial benefits. Part I outlines how traditional principles of bioethics are being challenged by existing bioethical rules and practices in the population genomics context. Parts 11,111, and IV use each case study to illustrate how issues with informed consent, Institutional Review Boards, and commercial benefits have emerged in practice, and how reforms addressing these areas are needed. Part V outlines ways in which the current genomics system could be brought more into line with the foundational principles of bioethics, and finally, I propose four avenues of reform for better bioinformatic governance.

I. BACKGROUND

A. The Common Rule and Informed Consent The Nuremberg CodeZ0first articulated research standards as international norms and the World Medical Association affirmed them in the Declaration of Helsinki." In the United States, these norms are implemented in the federal regulations known as the "Common Rule."'' The Common Rule applies to research conducted or supported by federal departments or agencies, or performed by an institution that has given the federal government "assurances7' that all of its human subjects research will comply with the rule." The rule requires that all such human subject research proposals be reviewed and approved by an ethics committee, the Institutional Review Board (IRB), and the rule specifies procedural and substantive criteria for the review.24 Institutional Review Boards (IRBs) are composed of "at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the [researching] i n s t i t u t i ~ n . "Thousands ~~ of IRBs have been formed over the last 25 years, mostly in large academic centers receiving federal finds for research, community hospitals, managed care organizations, and government agenciesz6 Some IRBs have also emerged as independent entities working outside of research institution^.'^ These bodies have 20. See GEORGEJ. ANNAS & MICHAELA. GRODIN, THENAZIDOCTORSAND THENUREMBERG CODE(1992). The text of the Code is available at http:l/206.102.88.1O/ohsrsite/guidelines/ nuremberg.html (last visited Jan. 25,2003) [hereinafterNUREMBERGCODE]. 21. THEWORLDMEDICALASSOC~AT~ON DECLARATION OF HELSINKI: ETHICAL I'RINCIPLES FOR MEDICALRESEARCH INVOLVING HUMANSUBJECTS (1964) (as revised by the World Medical Assembly in Tokyo, 1975, in Venice, 1983, in Hong Kong, 1989, in South Africa, 1996, and in Edinburgh, 2000), available at http:llwww.wma.netleIpolicy/l7cnote.pdf. 22.45 C.F.R. 5 46 (2002); BEAUCHAMP & CHILDRESS, supra note 3. 23.45 C.F.R. 5 46.101; Greely, supra note 17, at 738-39. 24.See45 C.F.R. 55 46.109-,117. 25. Id. ji 46.107. 26. JUNEGlBBS BROWN, INSPECTOR GENERAL, DHHS, INSTITUTIONAL REVIEW BOARDS:THE EMERGENCEOF INDEPENDENTBOARDS, OEI-01-97-00192, at i (1998), available at http:// oig.hhs.govloeilreportsloei-01-97-00192.pdf(last visited Jan. 25, 2003). 27. Id. W I N T E R 2003


broad authority over approval of research protocols on human s~bjects.'~ Before IRBs grant approval to a particular research protocol, the following requirements, inter alia, must be satisfied: (1) risks to subjects are minimized; (2) risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result; (3) selection of subjects is equitable; (4) informed consent will be sought from each subject;29(5) when appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects; and (6) when appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.jO Informed consent in human research is generally defined as the research subject's affirmative agreement to participate after being informed ofthe risks and benefits of the research." However, IRBs have the discretion to waive the informed consent requirement as long as (a) the research poses only minimal risk to the subjects, (b) the subjects' rights and welfare will not be affected by the waiver, (c) the research is impracticable without the waiver, and (d) when appropriate, the researchers provide subjects with additional information about the research after their participation.32

B. Calls for Reform Prompted by well-publicized cases involving the deaths of human research participants," the Department of Health and Human Service (DHHS) and the National Bioethics Advisory Commission (NBAC) recognized the need to make broad reforms to the current systemof ~versight.'~ In a series of recent reports, Expanded DHHS has determined that "the effectiveness of IRBs is in je~pardy."'~ workloads, resource constraints, and extensive federal mandates have contributed

to an atmosphere in which IRBs "review too much, too quickly, [and] with too ~ ~ found minimal ongoing IREi review of research, underlittle e ~ p e r t i s e . "DHHS trained board members, and independence threatened by conflicts of interest." In 1998, DHHS recommended recasting existing requirements to make IRBs more flexible and accountable, strengthening the monitoring of research, establishing education standards of IRB members, and requiring more i n d e p e n d e n ~ e .A~ ~ follow-up report in 2000 found that few of their recommendations had been implemented.39 A recent report by the Institute of Medicine examines the possibility of implementing an IRB accreditation system to monitor overall effectiveness of the IRB system.40 Citing widely recognized deficiencies in the oversight system, NBAC recently concluded that there ought to be an independent federal office to oversee and regulate all human subjects research, including privately funded research. NBAC's recommendation has three themes: first, that there should be fewer federal regulations and more guidance; second, that protections should focus on the most vulnerable participants and should tailor the level of protection to the It emphasized amount ofrisk; and third, that more research should be reg~lated.~' that informed consent should be a process, not a form.42 Generally two genetics-specific concerns have prompted calls for reform. First, using previously obtained biological samples for new research purposes without the renewed consent of the donors has increasingly come under fire. Traditional informed consent forms are designed to elicit consent for a specific research project, and some commentators argue that no person can give informed consent to unknown future research uses ofgenetic information. In a controversial article one group of bioethicists questioned the traditional practice of using clinical tissue samples for research without IREi review and without renewed consent of the donors.43This recommendation would have severely curtailed the A majority of the NBAC use of existing tissue samples for genetic re~earch."~ members recommended that signed consent to unforeseen research uses of

28. 45 C.F.R. $ 46.109(a). 29. The extent of informed consent required is discussed in id. $ 46.116. 30. Id. $5 46.107-,124; NBAC, supra note 2, at 69-70. 3 1.45 C.F.R. $46.116.Article One of the Nuremberg Code states, in part: The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to glve consent; should be so situated as to be able to exercise hee power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision

NUREMBERGCODE, supra note 20. 32.45 C.F.R. $46.1 16(d). 33. See, e.g.,Rick Weiss & Deborah Nelson, FDA Halts Experiments on Genes at Universily: Probe of Teen's Death Uncovers Deficiencres, WASH. POST,Jan. 22,2000,at A l . In the best known of these cases, an eighteen-year-oldsubject Jesse Gelsinger died as a result of his participation in a gene therapy study at the University of Pennsylvania. Id. 34. NBAC, supra note 2, at i. 35. JUNEGIBBSBROWN, INSPECTOR GENERAL,DHHS, INSTITUTIONAL REVIEWBOARDS: A TIMEFOR REFORMii (1998), available at http://oig.hhs.gov/oei/reports/oei-01-97-00193.pdf (last visited Jan 25, 2003).

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36. Id. 37. Id. For a discussion of individual conflicts of interest, see Kelch, supra note 8, at 286-87. 38. BROWN, supra note 35, at iii-iv. 39. JUNE Glees BROWN, INSPECTOR GENERAL, DHHS, PROTECTINGHUMANRESEARCH SUBJECTS: STATUSOF RECOMMENDATIONS 1-3 (2000), available at http://www.oig.hhs.gov/oei/ reportsloei-01-97-00197.pdf (last visited Jan. 25, 2003). 40. INST. OF MED., PRESERVINGPUBLICTRUST: ACCREDITATION AND HUMANRESEARCH PARTICIPANTPROTECTIONPROGRAMS (2001). available at h n p ~ I ~ ~ ~ . n a p . e d ~ o o k s / 0 3 0 9 0 7 3 2 8 6 / htmll (last visited Jan 26, 2003). 41. NBAC, supra note 2, at xi. 42. See id. at xvii (Recommendation 5.1);ANNAS& GRODIN, supra note 20; George J. Annas, Reforming Informed Consent to Genetic Research, 286 JAMA 2326 (2001). 43. Clayton et al., supra note 17, at 1790. 44. See, e.g., STORED TISSUESAMPLES, supra note 17; Greely, supra note 17.

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biological samples-"open consentv-may be an acceptable alternative to requiring informed consent for each specific use of the sample.45 Second, some bioethicists have advocated strong protections for the privacy of genetic information because of its unique and powerful status as some sort of "future diary."46 Many others, however, reject genetic exceptionalism, arguing that there is nothing to distinguish genetic information from other health information-such as data derived from medical records.47 Whether or not the "genetic exceptionalists" are correct in urging special rules for genetic information, it is clear that a risk to privacy exists. The disclosure of genetic information could harm individuals in terms of employment and health insurance opportunities,48 reputation, familial problems, and psychological stress.49 It also q a y "wrong" a person to leave private information open to the mere perusal of others.50 These concerns for privacy were the principal reasons for establishing NBAC." NBAC's response, however, has conflated informed consent with privacy by construing the Common Rule language in ways that help remove informed consent requirements for research on tissue samples, so long as the

45. See B ~ ~ L O G ~ C A L M A T E R I note A L SL,O~, at ~ 64-65 ~ ~ ~ (Recommendation 9). Commissioners Capron and Shapiro rejected the view that patients and donors should be allowed under any circumstances to consent to "any kind offuture study." Id. at 65 (note). Greely, supra note 17, at 764, stakes out a middle position. He would allow signed "permission" for unforeseen research with provisions stipulating the conditions of recontact, an absolute right of withdrawal at any time, time limits, limitations on availability of information to third parties, group permission requirements on top of individual permission, disclosure of commercial interests, confidentiality stipulations, and community benefits. Id. at 752-58. Still other bioethicists reject "open consent" unless all DNA samples are stripped of all identifiers. See, e . g , Annas, supra note 12. A n n a suggests that individuals might not give permission if they knew that the data were being used to study possible genetic correlations to conditions such as alcoholism or homosexuality. Id. at 2 3 4 7 4 8 . See, e.g., Annas, supra note 42. 46. Annas, supra note 12, at 2349. 47. See, e.g.,Philip R. Reilly, Laws to Regulate the Use ofGenetic Information, in GENETIC SECRETS: PROTECTMGPRIVACY ANDCONF~DENT~ALITY MTHEGENET~CERA 369 (Mark A. Rothstein SECRETS];Ssren Holm, There Is Nothing Special About Genetic ed., 1997) [hereinafter GENETIC supra note 14, at 97. Many opponents of "genetic Information, in GENETICINFORMATION, exceptionalism" advocate developing stronger privacy protections for all health information, genetic or otherwise. E.g.,Lawrence 0 . Gostin & James G. Hodge, Jr., Genetic Privacy andthe Low: An End to Genetics Exceptionalism, 40 JURIMETRICS J. 21,23 (1999); Henry T. Greely, The Revolution in Human Genetics: Implications for Human Societies, 52 S.C. L. REV. 377,388 (2001). 48. E.g., Curtis R. Naser, High Speed Genetic Testing Technology and the Computerization supra note 14, at 105; Ken R. Smith et al., Genetic of the Medical Record, in GENETICINFORMATION, Testing and Adverse Selection in the Market for Life Insurance, in i d , at 57. TANCREDI, DANGEROUS DIAGNOSTICS: THE 49. See, e.g , DOROTHYNELKIN& LAURENCE SOCIAL POWEROFBIOLOGICALINFORMATION (1 989); GENETIC S E C R E T S ,note S U47, ~ ~at~255-355. 50. Naser, supra note 48, at 113; A.M. Capron, Protection of Research Subjects: Do Special EPIDEMIOLOGY 81S, 83s (1991). Rules Apply in Epidemiology?, 44 J. CLMICAL supra note 10 (Letter of Transmittal to the President). 5 1. BIOLOG~CALMATERIALS,

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samples are coded to protect the identity and privacy of the individuals from whom they had been taken." Beyond this, the federal government has done little to protect most medical information, allowing the states and the keepers of that information to determine the level of privacy afforded to medical records." The Department of Health and Human Services ("DHHS") has recently issued new regulations to protect the Because the regulations focus on research privacy of medical inf~rmation.'~ studies that involve ''treatment,"s5 the regulations effectively exclude from protection the majority of genetics research, which typically has no medical treatment c~mponent.'~

C. Reframing the Analysis Population genetics challenges existing ethical structures. Existing proposals for reform, however, seem unconcerned that the problems raised by population genomics are not only scientific and ethical, but also political. They therefore require reframing in order to address neglected issues of power and political process. The powers to evaluate scientific potentials, weigh risks, formulate group identity, and allocate property rights all involve political dimensions. Bioethicists have the authority to govern this hybrid realm, but are they competent and Examination of the legitimate administrators of this new sphere of biopoliti~s?~' Human Genome Diversity Project, Iceland's Health Sector Database, and the Beth

52. Id. at 66-70; Greely,supranote 17, at 747 ("TheNBAC generally views these requirements loosely, notably by recommending that IRBs 'operate on the presumption' that research on coded samples is of minimal risk as long as confidentiality is protected . . . ."). 53. On state protections, see Charity Scott, Is Too Much Privacy Bad for Your Health? An Introduction to the Low, Ethics, and HIPAA Rule on Medical Privacy, 17 GA.ST. U. L. REV. 48 1 (2000). Minnesota goes further than most states to protect medical records that might be used in research. Its law requires that patients be notified and give written authorization for the use of their records in research, and this consent may be revoked at any time. Id. at 497-98. 54.45 C.F.R. $5 160-164 (2002). 55. The Privacy Rule specifies rules for the use and disclosure of protected health information created only "for research that includes treatment." Id. 5 164.508(t). 56. See Mark Barnes & Sara Krauss, The Effect of HIPAA on Human Subjects Research, 10 BNA's HEALTHL. REP. 1026, 1028-29 (2001) (recommending that "the best practice, nevertheless, would be for IRBs, institutions and researchers to require HIPAA authorizations for all human subjects research, regardless of whether that research includes medical treatment"). But see George J . A n n a , Medical Privacy andMedical Research-Judging the New Federal Regulations, 346 NEW ENG.J. MED. 216,2 18 (2002) (claiming that the HIPAA rules do cover all research uses of medical records). Changes to the research rules have been recently proposed. See 67 Fed. Reg. 14,776, 14,793-98 (Mar. 27,2002) (to be codified at 45 C.F.R. pts. 160, 164). 57. I use this term differently than, for example, Foucault, who used it to describe the exertion ofregulatory controls by the state on the bodies of its citizens. However, my definition of biopolitics in the area of genomics and bioinformation draws upon Foucault's account of "bio-power," and the historical process through which biological knowledge has become a tacit and strongpolitical force. See MICHELFOUCAULT, THEHISTORYOFSEXUALITY, VOLUMEI: AN INTRODUCTION1 3 5 4 5 (Robert Hurley trans., 1988).

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Winickoff

Israel-Ardais Collaboration illuminates three areas requiring attention: informed consent protocols, expert ethical review procedures, and allocations of comrnercia1 benefits. Governing structures in these areas require greater political sophistication as human genetics moves from individuals to groups.

11. POPULATION GENOMICS: THE HUMAN GENOME DIVERSITY PROJECT In the summer of 1991, population geneticists and evolutionary biologists from the United States called for a "worldwide survey of human genetic diver~ity."'~ The project's organizers predicted that such a study would produce "enormous leaps in our grasp of human origins, evolution, prehistory, and potential" and help establish "who we are as a species and how we came to be."'9 But indigenous groups opposed this "vampire project," and its funding has stalled indefinitely.@' This section summarizes these developments. By 1984, a group of geneticists had developed the idea of collecting blood, hair, and human tissue samples from "populations that have been geographically isolated or have a distinct culture and language."6' At the Project's first meeting in 1992, organizers agreed that samples "from between 400 and 500 populations" should be collected to create "'imrnortalized' cell lines for future analysis."62 By the winter of 1993, indigenous groups and NGOs became overtly critical , of the project. The Ottawa-based Rural Advancement Foundation International (RAFI), an advocacy group on biotechnology and intellectual property issues? argued that the project would exploit indigenous groups by patenting cell lines derived from their materials: it would divert money from basic health services in rural areas, and would permit the development of biological weapons with ~ ~ RAFI alerted the World Council of specific targeted c ~ m m u n i t i e s .After Indigenous Peoples and published its comrnuniquC, a heated debate emerged on an internet message board, "Native-L."6' Many saw "human diversity research" as an "inherently racist" activity that would lead to new and harmful "gene-based 'definitions' of race."66

58. L. L. Cavalli-Sforza et al., Call for a Worldwide Survey of Human Genetic Diversily: A Vanishing Opportunily for the Human Genome Project, 1 1 GENOMlCS 490,491 (1991). 59. Id. 60. See Margaret Lock, Genelic Diversity and the Politics ofDi/ference, 75 CHI.-KENTL. REV. 83,92 (1999); Jenny Reardon, The Human Genome Diversily Projecf: A Case Study in Coproduction, 31 SOC.STUD.SCI.357, 358 (2001). 720, 720 (1994). 61. Patricia Kahn, Genetic Diversily Project Tries Again, 266 SCIENCE 62. Lock, supra note 60, at 91. 63. Id. at 92-93; Reardon, supra note 60, at 369. 64. Reardon, supra note 60, at 369. 65. Native Net is discussed in Reardon, supra note 60, at 369-70, and Lock, supra note 60, at 90. As of March 2002, the archive of these exchanges could be accessed at http://nativenet. uthsCsa.edu/archive/nl/hgdp.html[hereinafter Native Net]. 66. Kahn, supra note 61, at 721.

43 JURIMETRICS

A. Innovations in Informed Consent In response, the North American Regional Committee of the Diversity Project developed a "Proposed Model Ethical Protocol For Collecting DNA Samples" and the concept of "group consent."67 Group consent, they argued, appropriately incorporated the guiding ethical values of the project: "informed consent," "respect for the participating population's culture," and "adherence to international standards of human rights."68 The Model Protocol described the rationale for requiring group consent as follows: Many of the populations that might participate in the HGDP are politically or economically marginal in their countries. They have faced discrimination, oppression, and even genocide. Under such circumstances, it cannot be ethically appropriate to sample some members of a group when the group itself has not agreed to participate in the HGDP. Such methods would themselves be another form of attack on the autonomy of the population.69 Members of the HGDP ethics committee expressed hope that group consent as outlined in the Protocol would replace the protection of individuals as the dominant paradigm in the management of genetics research with the protection of both individuals and groups.70 The "group consent" proposals generated an even deeper set of criticisms. If "groups" were going to give their consent for these studies, the researchers would first have to create the groups, and indigenous rights organizations worried that "expert" definitions of indigenous groups would construct their identity in ways that actually threatened the group's security and a ~ t o n o m y . ~In' general, they complained, "the group from whom consent must be sought is defined by the researchers ' sampling riter ria."^' The ability to determine the definition of one's own group and what . constitutes membership in that group is at the heart of autonomy. Drawing upon his work on democratic power-sharing in South Africa, Arend Lijphart has stated that the "policy of artificially forcing people into racial and ethnic categories," especially when it is "unclear what the true dividing lines are . . . entails not only

67. Symposium,Proposed Model Ethical Protocolfor Collecring DNA Samples, 33 Ilous. L. REV. 1431, 1433, 1443-47 (1997) [hereinafter Model Protocol]. 68. Id. at 1436. 69. Id. at 1443. 70. In this way, the Protocol could become a model not just for the HGDP, but also for other population genetics projects, such as the study of families with certain diseases. Seeking to construct

a more flexible "group consent" mechanism, others have proposed additional guidelines and taxonomies of different types of groups to aid the process of group consent, calling the process "community review."See, e.g.,Morris W. Foster et al., The Role of CommunipReview in Evaluating the Risks of Human Genetic Variation Research, 64 AM. J . HUM. GENETICS 1719.1722-23 (1999); Eric T. Juengst, Commentaty: What "Communily Review" Can and Cannot Do, 28 J.L. MED.& ETHICS52, 54 (2000); Richard R. Sharp & Morris W. Foster, Involving Study Populations in the Review ofGenetic Research, 28 J.L. MED.ÐICS41,42 (2000). 71. Reardon, supra note 60, at 374-77. 72. Id at 375.

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potential discrimination against groups but, as a rule, also the assignment of individuals to specific groups [when] individuals may well object to such labeling."73 "Self-determination" is more properly the process by which groups "are allowed, and even encouraged, to emerge spontaneously-and hence to define t h e m ~ e l v e s . " ~Although ~ it marked an important step towards the recognition of group autonomy and culture, the Model Ethical Protocol failed to recognize how it pre-defined biopolitical groups in ways that inherently limited self-determination and autonomy.

B. Legitimacy of Ethical Review In addition to the issues of self-determination and autonomy that the group consent proposals created, new problems involving the political legitimacy of the oversight of the research emerged. Critics worried that beyond having the power to define "group" populations, researchers also retained the power both to recognize who the "culturally appropriate authorities" ought to be and to decide ultimately whether both individual and group consent had been given.75 The Protocol offers "some general advice" as to how researchers and IRBs should locate these "culturally appropriate governing a ~ t h o r i t i e s . "The ~ ~ Protocol states that "group leaders" should be vested with the authority to grant group consent, or where those leaders don't exist, consent should be granted by "consensus ofthe , entire com~nunity."~~ If no clear authorities exist, "the researcher may be able to present information and seek approval kom active members of the comm~nity."'~ This system seemed politically unacceptable and also unworkable in many cases. Who would be the relevant authority for groups like Ashkenazi Jews, IrishAmericans, "Blacks," or people who speak Cree?79 Decisions as to whether individual consent was properly given in each instance and whether the group consent process had been met would inevitably contain ethical and political judgments. The realms of the scientific and the social, ethical, and political "are inextricably interconnected and come into being t~gether."'~ Out of these debates about group consent and expert ethical oversight, however, important principles for a more politically acceptable form of governance evolved. Cultural membership and participation is important to modem freedom-seeking citizens, and the HGDP suggests that individuals and groups would be better served by a more democratic model that embodies the principles of accountability, responsibility, and representation in ethical review.

73. Arend Lijphart, Ethnic Minoritres in Power-Sharing Systems, in THERIGHTS OFMINORITY

CULTURES 275,284 (Will Kymlicka ed., 1995). 74. Id at 280. 75. Native Net, supra note 65. 76. Model Protocol, supra note 67, at 1444. 77. Id. 78. Id. The protocol gives a "parish priest" as an example of an "active member." Id. 79. Reardon, supra note 60, at 375-78; Juengst, supra note 70, at 54. 80. Reardon, supra note 60, at 38 1.

4 3 JURIMETRICS

Accountability. The bodies that make decisions ought to be accountable for what they do. Ethical overseers have a "responsibility to communicate, upon request, a narrative of the actions undertaken in the context of the circumstances that obtained at the time."" Responsibility. Accountability makes possible the ascriptions of blame or credit inherent in responsibility. Mistakes or misjudgments ought to have political and legal consequences for ethical overseers. Representation. Representation is important for legitimacy generally, and it is an important procedural protection of donors' substantive interests. The governance of biological information, and all human subjects research generally, ought to include the subjects. The less politically organized a group of potential research subjects is, the more it may be incumbent upon researchers to facilitate group autonomy and democracy. The principle may have to make compromises in terms of proxy mechanisms. An overtly political model, rather than an elite or expert model of bioethical oversight, is appropriate. Regulations instruct IRBs to approve a research proposal only if the IRB judges that the risks are reasonable in relation to potential benefit^,'^ but "[tlhe current regulations do not further elaborate how risks and potential benefits are to be assessed, and little additional guidance is available to IRBs."" Neither the Common Rule nor NBAC's attempts to guide IRBs deal with complicated questions of evaluating just who benefits and by how much, and whether the particular allocations of benefil inherent in a protocol comport with justice and beneficence principles. Instead, current rules and proposals treat risks and benefits as quantitative and one-dimensional entities. Characterization of risk-benefit analysis as a fundamentally "rational," expert process instead of a "political" one involving normative assumptions insulates judgments from social criticism and political p r o c e ~ s . 'As ~ IRBs allocate the commercial benefits of research to researchers or corporations, their status as "independent" expert bodies becomes suspect. To improve the IRBs, some commentators proposed adding more members developing guidelines for conflicts of intere~t,'~ from the volunteer c~rnmunity,'~

8 1. Holdsworth, supra note 14, at 86; see Dick Holdsworth, Accountability: The Obligation to 42 (Ruth F. Chadwick ed., 1994). Lay Onese[fOpen lo Criticism, in ETHICSANDTHE PROFESSIONS 82. NBAC, supra note 2, at 74-75. 83. Id at 71. 84. See, e.g.,Rachelle Hollander, Expert Claims andSocial Decisions: Science, Politics, and Re~ponsibility,in ACCEPTABLEEVIDENCE:SCIENCE AND VALUESIN RISK MANAGEMENT 160 (Deborah G. Mayo & Rachelle D. Hollander eds., 1991); SHEILA JASANOFF, THEFIFTHBRANCH: SCIENCE h V I S E R S AS POLICYMAKERS (1990); SHEILA JASANOFF, RISK MANAGEMENTAND POLITICALCULTURE (1986); W~NNER, supra note 18. 85. 45 C.F.R. 8 46.107(d) (2002) already provides that "[elach IRB shall include at least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution." The NBAC recommends that 25% of IRB members be people "who represent the perspectives of participants, . . . who are unaffiliated with the institution, and . . . whose primary concerns are in nonscientific areas." NBAC, supra note 2, at xvi

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and educating and accrediting IRBs.'~ However, political legitimacy requires a deeper set of changes.

C. Allocations of Commercial Benefits Western researchers and major drug companies, in search of unusual DNA sequences in isolated human populations, have begun collecting blood samples in remote areas of the world in an effort to produce medications from unknown gene allele^.^' Certain well-publicized cases of what critics called "biopiracy" forced the HGDP's ethics committee to deal with the issue of intellectual property rights. In the early 1990s, for example, the U.S. Department of Commerce submitted a patent application on the cell line of a woman from the Guaymi, an The woman who was illiterate and unschooled, indigenous group in Panan~a.'~ was said to have given "informed oral consent" to the research, even though neither the tribe nor the woman knew anything about the development of the cell line or the patent application.* RAFI and the Guaymi demanded the withdrawal of the application, and the Department of Commerce acq~iesced.~' In another case, biomedical researchers patented the T-lymphotrophic virus found in blood of the Hagahai people in Papua New Guinea, believing that it could be developed into a diagnostic tool or vaccine for certain types of leukemia.92 The researchers had allegedly negotiated a profit-sharing agreement with the Hagahai, a tribe that had had no contact with outsiders until 1984, when some tribe members sought help for an illness that afflicted the g r o ~ p ?RAFI ~ called the incident an example of "biopiracy" and human "bioprospecting," even as The Economist considered these charges "blather."94 The patent turned out to hold little commercial value, and NIH relinquished its rights to the patentgs In response to these incidents. the Model Ethical Protocol specified that the research must "not only [do] no harm to the participating communities, but, where possible, bring them benefits."96The Protocol announced that the HGDP "will not

(Rewmmendation3.10). Although, asingle person could fulfill all ofthesecategories, someone from all categories must be present at the IRB meetings. Id 86. NBAC, supra note 2, at xv (Recommendations 3.7 and 3.8). 87. Id. at xiv (Recommendations 3.3 and 3.4); see also INST.OF MED.,supra note 40, at 16 (Accreditation ought to be "widely accepted as a mark of excellence. It should also serve as an educational tool to raise the median overall performance [of IRBs]."). 88. See, e.g., John Pomfret & Deborah Nelson, An Isolated Region's Genetic Mother Lode, WASH. POST,Dec. 20,2000, at Al. 89. Lock, supra note 60, at 99-100. 90. Id. at 99; Margaret Lock, The Alienation ofBody Tissue and the Biopolitics oflmmortalized Cell Lines, 7 BODY& SOC'Y63 (2001) (presenting a more anthropological approach). 91. Lock, supra note 60, at 99. 92. See Kara H. Ching, Note, Indigenous Self-Determination in an Age of Genetic Patenting: Recognizing an Emerging Human Rights Norm, 66 FORDHAM L. REV. 687,701 (1997). 93. Id. 94. See, e.g.,Biolechnology: Patent Blather, ECONOMIST, Nov. 25, 1995, at 87. 95. Ching, supra note 92, at 702. 96. Model Protocol, supra note 67, at 1436.

43 JURIMETFUCS

,

profit from any commercial uses of samples it gathers or knowledge derived fiom those samples"97 and that the HGDP "has vowed to ensure that, should comrnercia1 products be developed as a result of the HGDP's collections, a fair share of the financial rewards shall return to the sampled populations. Any researchers who take part in the HGDP must accept these two point^."^' Although the Protocol does not create a definite mechanism for upholding these pledges, it suggests three possible approaches: (1) researchers could not "make use of the HGDP's samples or data in a patent application or a commercial product without the express written permission of the sampled populations involved, . . . subject to whatever conditions they impose for that permi~sion;"~~ (2) "anyone making commercial use of the HGDP's samples would pay a set percentage royalty . . . for the benefit of the sampled p o p ~ l a t i o n s ; " 'and ~ ~ (3) "anyone making commercial use of the HGDP's samples or data would have to negotiate a reasonable financial payment with a trustee for the sampled populations, with the proceeds for the population's benefit.""" The duty to provide some sort of direct benefit to the sampled community is an advance over the Common Rule, but, in some ways, HGDP Protocol only highlights the problems of representation. Who would have the ultimate power to define and recognize whether a deal had been struck and under what terms? Who would be the "culturally appropriate authorities" in groups that were constructed by the researchers? How would procedural justice be insured in this process, which is at least superficially similar to previous negotiations for property rights between indigenous groups and colonists?

111. STATE GENOMICS: ICELAND'S HEALTH SECTOR DATABASE In December 1998, the Icelandic Parliament, the Althingi, passed the Act on a Health Sector Database (HSD Act).'02 The law allowed the Minister of Health in Iceland to grant a license to a private company to construct an electronic database containing all of the health records in the national health care system.'03 The government granted the license to Decode Genetics in January 2000, and the for-profit Delaware corporation plans to use the license to construct one piece of a centralized database linking medical records with genealogical and genetic

97. Id. at 1466. 98. Id. 99. Id. at 1466-67. 100. Id. at 1467. 101. Id. 102. Acton aHealthSector Database, no. 13911998,availablear h~p:lhrunnur.stjr.islinterprol htr/htr.nsUpages/gagngr-log-ensk(passed by the Albingion Dec. 17, 1998)(last visited Feb. 3,2003) [hereinafter Act on a HSD]. 103. Id. 4 11, art.4.

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i n f ~ r m a t i o n . Both ' ~ ~ the law and the license have generated strong criticism in Iceland and abroad.lo5

I

A. Innovations in Informed Consent

society.lo8Since it is unclear whether technology can be relied upon to protect privacy, many bioethicists reject "open consent" unless all DNA samples are stripped of all identifiers.lW Much of the ethical, legal, and political debate in Iceland has centered on this privacy issue and the adequacy of state-of-the-art encryption systems.

1. Open Consent 2 . Presumed Consent

Embedded in the HSD Act is the notion of "open consent," about which no specific rules pertain either in the United States or internationally. In an open consent system, the donor grants "consent" to use his or her tissue or information in any future experiments that the researchers may conduct. The HSD Act granted Icelanders' "consent" to use their health records for any research purposes that DeCode or one of the licensees wishes to conduct in the future. Traditionally, research participants must be informed of all potential risks or benefits of the research, so long as they are more than de minimis. By definition such informed consent can be obtained only for specific research projects for which meaningful information about the risks and benefits has been provided.Io6 This traditional consent was impossible for Decode's research, which requires an open license to use this information to search for correlations between genotypes and any number of present and future conditions. Even if "open consent" could be considered informed, it limits decision making. Because the Act leaves uses unspecified, people cannot state how they ' want their information used. For example, perhaps individuals would not give consent if they knew that the data would be used to study possible genetic bases Moreover, new technologies may be exposing for alcoholism or homo~exuality.'~~ research subjects to future informational privacy risks that are difficult to weigh. Encryption software has yet to be written, and medical histories and genetic and genealogical data will be merged making identification possible in such a small

A second way in which the HSD Act pushes on traditional norms of informed consent is in its use of "presumed consent." The HSD Act allows the licensee to collect medical records of every Icelander without any affirmative informed consent of individuals."' As company officials state: "[plresumed consent is a nebulous concept, but . . . we regard it as the consent of society to the use of If people do not health care information according to the norms of so~iety.""~ want their information used, they must "opt out.""' An Icelander can "opt out" only by sending a signed form to the Ministry of Health.'l4 The information of the deceased will automatically be included, despite the potential privacy interests of relati~es.''~ Individuals cannot withdraw any information once it has been entered into the database.'I6 In response to the criticism that presumed consent is violative of informed consent, DeCode invoked arguments about community consent that had emerged in the context of the Human Genome Diversity Project.'" However, the HGDP Model Protocol deployed group consent to assuage the concern that individual informed consent alone failed to protect the autonomy of minority groups targeted by research. In contrast, executives of DeCode deployed "community consent" to assert the power of the majority and to deny the need for informed consent of individuals.

108. Iceland's population isestimated atroughly 280,000. See ICELANDINF~GURES~OOO-2001, at 6 (Dec. 2000), available at http://www.statice.is/statistic/iceIand2000.pdf (last visited Feb. 2, 2003). supra note 10, at 59-61. 109. See, e.g.,BrOLOGICAL MATERIALS, 110. Thus, DeCode and the Icelandic government tout encryption mechanisms as a "very secure" answer to bioethical concerns. Bill on a Health Sector Database, available at http:// brunnur.stjr.is/interprohtrhtr.nsUpag~agnagr-ensk (last visited Jan. 26,2003) [hereinafter Bill on a HSD]. Opponents of the Act cite expert opinions questioning the efficacy of this encryption. See Ross Anderson, The DeCODE Proposal for an Icelandic Health Database 6-7 (Oct. 20, 1998), available at http:llwww.Ap.cl,cam.ac.uWAp/users/rjal4/icelandpdf ( a s visited Feb. 2, 2003). 11 1. Patients must opt out. Act on a HSD, supra note 102 g 111, art. 8. 112. Gulcher & Steftinsson, supra note 11, at 1827. 113. Act on a HSD, supra note 102 8 111, art. 8. 114. Id. 115. Id.; Bill on a HSD, supra note 110, at "On Art. 8." This aspect ofthe HSD Act is currently being challenged in the Icelandic courts. Ragnhildur Gudmundsd6ttir v. The Icelandic State, District Case No. E-44261200 1. 116. Article 8 is silent on the removal of information. Act on a HSD, supra note 102, at 5 111, art. 8; Bill on a HSD, supra note 110, at "On Art. 8." 117. Gulcher & Stefhnsson, supra note 11, at 1827.

104. Form S-I/A, Registration Statement under the Securities Act of 1933, DeCode Genetics, Inc., p.36 (filed June 19,2000), available at http://www.shareholder.com/Common/Edgar/l022974/ 893220-00-772100-00.pdf (last visited Jan. 26,2003) (print version on file with author). 105. See, e . g , ROSE,supra note 15; Ruth Chadwick, The Icelandic Database-Do Modern Times Need Modern Sagas?, 319 BRIT.MED. J. 441 (1999); Nigel Duncan, World Medical Association Opposes Icelandic Gene Database, 318 BRIT.MED.J. 1096 (1999); Martin Enserink, Opponents Criticize Iceland's Database, 282 SCIENCE 859 (1999); Mike Fortun, Mediated & SOC'Y 139 (2001); Henry T. Speculations in the Genomics Futures Markets, 20 NEWGENETICS Greely, Iceland's Plan for Genomics Research: Facts and Implications, 40 JURIMETRICS J. 153 (2000); Ragnheidr Haraldsd6ttir, Icelandic Gene Dafabase Will Uphold Patients 'Rights,3 18 BRIT. MED.J. 806 (1999); Bernard Palsson & Snorri Thorgeirsson, Decoding Developments in Iceland, 17 NATUREBIOTECHNOLOGY 407 (1999); Skuli Sigurdsson, Yin-Yang Genetics, or the HSD deCODE Controversy, 20 NEWGENETICS & SOC'Y103 (2001); R. C. Lewontin, People Are Not Commodities, N.Y. TIMES,Jan. 23, 1999, at A19. A history of the Act's opposition can be found on the website of MANNVERND, the Association of Icelanders for Ethics in Science and Medicine, at http:/l www.mannvernd.islenglish/index.html. 106. FADEN& BEAUCHAMP, supra note 2, at 235-73. 107. See, e.g.,George J. Annas, Rules for Research on Human Genetic Variation-Lessons from Iceland, 342 NEWENG. J. MED. 1830,1832 (2000); Patricia(Winnie) Roche et al., The Genetic Privacy Act: A Proposal for National Legislalion, 37 JURIMETRJCSI . 1, 7-8 (1996).

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3 . Analysis The combination of presumed consent and open consent is especially autonomy-limiting. Personal autonomy in generating and controlling biological information, or "bio-a~tonomy,""~necessitates that there be more stringent requirements in obtaining the informed consent of research subjects. Encryption technologies may reduce risks of unauthorized third-party use and mitigate privacy concerns, but they do not h l l y honor the autonomy interests of research volunteers. A clear informed consent requirement recognizes that medical information is generated out of a confidential relationship between a patient and a doctor, whose special duties demand this standard of care and respect. The value of full information and choice, in order to avoid involvement in practices with which we disagree, has great social importance.1i9

B. Legitimacy of Ethical Review In Iceland, the free market of ideas was dominated by the commercially interested. The technical complexity of the proposed research and Decode's economic power shaped a public debate that confused and misled the populace and the legislature. Although DeCode and the Icelandic government have cited the public debate in Iceland as evidence of "community consent," and some ethicists have described the public debate as "extensive" and " ~ r i t i c a l , " ' ~ ~ [tlhis [debate] w a s a volatile mixture o f messy ethical questions, lofty medical a n d economical promises, and politics, in a society which possessed neither a vocabulary nor a tradition to discuss biotechnology, bioinformatics o r the regulation o f biomedical research, and certainly had n o international models with which t o discuss novel genomic database issues. . . . Instead of acknowledging the inherent complexities o f the matter the debate soon became starkly polarized."'

DeCode ran a public relations campaign that brought "information sessions" across the country to build public approval.'22 Technical complexity of the

118. German courts have spoken of a "right of informational self-determination," which involves the right to control what information is collected or generated and the right to control further disclosures of information. Madison Powers, Privacyandthe ControlofGeneticInformafion, T THE GENETIC FRONTIER: ETHICS,LAW,AND POLICY 77 (Mark S. Frankel & Albert H. Teich eds., 1994). 119. Many of us like the idea ofcontributing to the common good by participating in scientific research studies, especially where there is no extra bodily intrusion and no risk of physical harm. However, the calculus might change as we find out more about the particular research that is occurring. Do we agree with the goals ofthe research? What if the research is on the genetic basis of intelligence, and plans to investigate the role of genetic differences to explain differences in IQ scores across different ethnic groups? Will my bioinformation be shared openly? What if the research will be conducted by a for-profit company that refuses to share donated bioinformation with academic researchers? What if our tissue might be used in human cloning experiments? Many people refuse to invest money in companies with practices to which they object. 120. Pfilsson & Rabinow, supra note 15, at 168. 121. Sigurdsson, supra note 105, at 106. 122. Personal interviews with MANNVERND staff in Reykjavik, Iceland (Summer 2000).

204

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bioinformatic research paradigm, encryption technology, and lack of resources made it difficult for opponents to dissent. Despite active opposition by the Icelandic Medical Association and the Association of Icelanders for Ethics in Science and Medicine (MANNVERND), DeCode controlled public d i s c ~ s s i o n . ' ~ ~ Asymmetries in technical expertise, information, and financial power led to an outcome that privileged DeCode over individual^.'^^ Thus, the Health Minister dismissed the sitting National Bioethics Committee, which had taken measures to reject Decode's research proposal for lack of informed consent, and reconstituted it with a smaller and more amenable ~ o r n r n i t t e e .The ' ~ ~ Minister of Health accomplished this by promulgating new regulations that effectively disbanded the sitting committee.'26These regulations reduced the number of committee members from seven to fivei2' and abolished nominations from independent institution^.'^^ The sole dissenter from the earlier committee remained the chairman of the committee. When possible conflicts of interest due to close contacts with DeCode were discussed in the press,i29the chairman's response was to request that the vice-chairman also attend the meetings. IJ0

123. Id. 124. It appeared that the government had been captured by commercial interests. The former President of Iceland was on Decode's board of directors until shortly before the HSD Act passed. Fortun, supra note 105, at 152-53. DeCode drafted the HSD legislation and nearly succeeded in pushing it through Parliament before any public debate had occurred. See Jbrunn Erla Eyfiord et al., deCODE Deferred, 16 NATUREBIOTECHNOLOGY 496,496 (1998). MED. J. 720 (1999), 125. The History of the National B~oethicsCommittee, 85 ICELANDIC available at http:Nw.mannvernd.is/englishlnews/imj.nbc.hl#histo(lastvisitedJan. 26,2003); Vilhjfilmur Rafnsson, Editorial, On the Two Year Existence of /he National Bioelhics Cornmiltee of MED.J. 679 (1999), available at http:N the Minister of Health and Social Securify, 85 ICELANDIC www.mannvernd.is/english/news/imj.nbc.html#editorial (last visited Jan. 26, 2003). The old National Bioethics Committee was appointed by the Minister of Health based on nominations from the Faculty of Medicine at the University of Iceland, from the Institute of Ethics the University of Iceland,the Institute ofBiologytheUniversity ofIceland,the School of Law at the U~~iversity of Iceland, the Icelandic Nurses Association and the Icelandic Medical Association Id. 126. Rafnsson, supra note 125, at 679-80. 127. Id. 128. Of the new committee members, the chair and one other member were appointed directly by the Minister of Health, one nominated by the Minister of Education, one by the Minister of Justice, and one by the Director General of Public Health. Id. 129. Id. 130. The Icelandic medical community widely criticized these changes. See A Resolution of the MED.J. 721 (1999). Board of Directors of the Icelandic Medical Association, 85 ICELANDIC The new method of appointing members to the committee has been criticized. In particular, it has been doubted that a committee established by three ministries and the Director General of Public Health can be considered independent. Some call it the Bioethics Committee of the Government. The Minister of Health has rejectedall criticismson the new committeeand explains that the clmngesaremade according to suggestionsfrom the Director General of Public Health Rafnsson, supra note 125, at 679-80.

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Disbanding the committee was not unlawful, as the committee was within the Ministry's regulatory power."' Nevertheless, this action, more than any other, brought into question the political legitimacy and independence of expert ethical review in this context.I3' The public received no information as to why the old committee voted down the proposal or why the new board voted in its favor,')) undermining trust in the system of ethical oversight: The secret rush to establish anew National Bioethics Committee seems to have broken most o f the basic principles of trust. If those changes were made to increase the trust in the Bioethics Committee by patients, by the public and by the scientific community, the Minister of Health has failed.'34

C. Allocation of Commercial Benefits By seizing control of the medical records of all Icelandic citizens, the government exploited its citizens' health information.lJ5In the Notes to the Act, the Icelandic Parliament asserts that "Tdlue - to the nature of the data and their origin [Icelandic health records] cannot be subject to ownership in the usual sense. Institutions, companies or individuals cannot therefore own the data [because tlhey exist primarily due to the treatment of patient^."'^^ This language is mere formalism: access, use, and control are nothing but the traditional incidents of property."' Thus, the government markets this personal medical information at the same time as it denies that the information can be owned. Next, the govenunent, still denying the proprietary aspects of the information, declared the "[r]ecorded data on the health of the Icelandic people [to be] a natural resource which should be preserved and used to yield benefits as far as possible."'3s Once considered a private record between patient and doctor, medical records have become a collective resource to be mined. The Parliament explained that

131. See Rafnsson, supra note 125, at 679-80. 132. Id. 133. Id. 134. Id. 135. The government asserted control and use over these records in four clean steps. First, the Act authorizes the Minister of Health to grant "an operating license to create and operate a health sector database" subject to some conditions. Act on a HSD, supra note 102, 5 11, art. 4. Second, as long as the licensee has "the consent of health institutions or self-employed health workers," and certain privacy precautions are instituted, "the licensee may be provided with data derived from medical records for entry onto a health sector database." Id. 5 111, art. 7. Third, the Act establishes acceptable uses of this database of medical information, and limits access. Id. 5 IV. In addition, the licensee may "process data. . . to develop new or improved methods of achieving better health," but it may "not grant access to data on the database"; and finally, "the licensee is authorised . . . to use the data on the database for purposes of tinancial prof t" subject to various privacy precautions. Id. g N, art. 10. 136. Bill on a HSD, supra note 110, at "I. Introduction." 1232 (7th ed. 1999); JOSEPH WILLIAMSINGER, 137. See, e.g., BLACK'SLAW D~CTIONARY ENTITLEMENT: THEPARADOXES OF PROPERTY 8 1-84 (2000). 138. Bill on a HSD, supra note 110, at "I. Introduction."

[i]t is . . . fair and a duty to utilise the data in the interests o f the health sciences and to promote public health. This can best be done by the government authorising the creation and operation o f a single centralised database, in which these data would be collected and where they would be processed.'39 The implication is that the Health Sector Database and the DeCode license represented "the best" way to maximize the commercial value of this "resource." Besides the impropriety of transferring value from the individual to a company while trying to convince the donors that what they are donating is worthless, the Act gives little assurance that this donation will "promote public health" or benefit the people of Iceland. Some believe the government should have, at the least, demanded more fi-om the company.'40

IV. CLINICAL GENOMICS: THE BETH ISRAELARDAIS COLLABORATION Iceland's license to DeCode Genetics exemplifies how genomics and bioinformatics are giving birth to new business models that require massive aggregations of genetic material and information. In the United States, where health institutions have come upon difficult financial times, hospitals are beginning to explore ways to generate revenue by tapping into the financial promise of the biotechnology industry. In particular, hospitals have begun to realize that they are uniquely poised to be the suppliers of tissue and medical information for the new industry. The Beth Israel Deaconess Medical Center (BI) in Boston is a major teaching affiliate of Harvard Medical School and a member of CareGroup. BI engages mostly in patient care, biomedical research, and teaching. Located in the heart of Boston's medical community, it annually serves more than half a million patients. It "is the third largest recipient of biomedical research funding from the National Institutes of Health."14' In September 2000, BI announced plans to collaborate with Ardais C o r p o r a t i ~ n . 'Participating ~~ hospitals like BI will give Ardais human tissue samples from biopsies (or other extractions of biological material) along with coded information from medical r e ~ 0 r d s . The I ~ ~ real commercial value lies not in the tissue alone, but rather in the "annotations," that is, the pieces of medical

139. Id. 140. Annas, supra note 107, at 183 1; Greely, supra note 105, at 190; personal interviews with MANNVERND staff, supra note 122. 141. See http://www.bidmc.harvard.edu/general-info (last visited Jan. 26, 2003). (last visited Jan. 26,2003). The 142. See http:llwww.ardais.com~national~initiativdindex.hl enterprise now includes Duke University Medical Center, Maine Medical Center, and the University of Chicago. Id 143. See h t t p : N w w w . a r d a i s . c o m I n a t i o n a l - i n i t i a t i v ~ d s h t m (last visited Jan. 26, 2003).

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information that come with it.144Ideally, each tissue sample will come to Ardais with 300 pieces of data about the patient.145The data will typically include history of illnesses and medications, family history, age, and "race."'46 The health data will be "abstracted" from patients' health records and transferred, without name or date of birth, to standard forms.'47 BI will do this work and Ardais will reimburse the hospital for this labor.I4' Two members of Ardais' Scientific Advisory Committee are also members of the BI physician staff.Iq9 BI treats the human tissue and the medical information as its legal property.Is0 BI transfers "the use" of the tissue to Ardais through a license.lsl In return, BI receives an undisclosed proportion of Ardais' revenues and a small equity share ~ payments will help support the hospital's research in the ~ o m p a n y . " The activities but will not support hospital adrnini~tration."'~~ BI researchers themselves will retain a certain number of samples for ongoing studies.154 Ardais claims to have "developed a number of organizational structures and functions to achieve the highest ethical standards in all of its operation^."'^^ The IRB at the BI has required that patients' interests be protected by stripping identifiers before sending the annotated tissues to Ardais, using a data encryption system by Ardais as a "firewall" against third-party intrusion and obtaining informed consent from participants.Is6

A. Innovations in Informed Consent 1 . Property Waivers Traditionally, a consent form has been a legal mechanism to ensure that the autonomy and privacy of the research subject are not violated by research uses of the subject's body. However, the fourth page of the informed consent form used

144. Telephone interview with Stuart Schnitt, M.D., former Vice-President and Director of Medical Operations at Ardais Corp. and Director ofsurgical Pathology at the Beth Israel Deaconess Medical Center, East Campus (Nov. 15,2000). 145. Id. 146. Id. 147. Id. 148. Id 149. See Membership of Ardais's Board of Directors, at http:Nw.ardais.comlcorporatel lead-scientific-advisory.html (last visited Jan. 26,2003). Harold Dvorak, Chief of Pathology at BI, is also the BI's principal investigator for this collection project. Id. 150. Schnitt interview, supra note 144. 15 1. Id BI also licenses Ardais to sub-license tissue. These users-biotechnology companies, pharmaceutical companies, and academic researchers-will provide cash revenue to the company. Id. 152. Id. 153. Id. 154. Id. 155.See ARDAIS, BIOETHICS PRNCIPLESAND P R A C T I C E S , ~http://w.ardais.com/donor-role/ ~ index.html (last visited Jan. 26,2003). 156. Telephone interview with Barry Eisenstein, Beth Israel Vice President for Technology Transfer and Professor of Medicine, Harvard Medical School (Oct. 24,2000).

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by Ardais and BI contains an unconditional gift of a patient's property rights in biological samples. The form states: You also understand and agree that the tissue you donate as a participant in this research program becomes the permanent property of the Beth Israel Deaconess Medical Center. Beth Israel Deaconess Medical Center has no program to compensate you in the event product testing or commercial development takes

2. Legal Enforceability It is unclear if a property conveyance in an informed consent form is legally enforceable. Since there is no consideration, it must be a gift rather than a traditional contract. Thus, the agreement reads "you also understand and agree that the tissue that you donate as a participant in this research program becomes the permanent property of the Beth Israel Deaconess Medical Center."'58 Since the donor retains a right to withdraw from research at any time, it is a "restricted gift" of rights to access, use, and transfer. However, public policy may forbid using an informed consent form in the clinical research context to make an effective gift. An attorney, for example, may not induce a client to make a gift to the attorney with a form prepared by the attorney.159In the legal profession, such self-dealing gives rise to an action for m a l p r a ~ t i c e . ' ~ ~ In Moore v. Regents of the University of C a l i f r n i ~ , the ' ~ ~California Supreme Court tried to adapt principles of informed consent to tissue donations. In the course of treatment for a rare condition called hairy-cell leukemia, John Moore consented to the removal of "extensive amounts of blood, bone marrow aspirate, and other bodily substance^."'^^ However, Moore's physician, who was "aware that 'certain blood products and blood components were of great value in a number of commercial and scientific efforts,"' did not reveal these facts and did not inform Moore of his research with Moore's cells.16' The physician established a cell line from Moore's T-lymphocytes, a type of white blood cell that produces lymphokines-proteins that regulate the immune system and have potential 157. Beth Israel-Ardais Informed Consent Form, at 4 (on file with author) [hereinafter BI Informed Consent Form]. 158. Id. (emphasis added). R. 1.8(c) cmts. (2001) (stating that "[a] lawyer 159. See MODELRULESOF PROF'LCONDUCT shall not prepare an instrument giving the lawyer or a person related to the lawyer as parent, child, sibling, or spouse any substantial gift from a client"). Comment [2] states: "A lawyer may accept a gift from a client, if the transaction meets general standards of fairness. . . . If effectuation of a substantial gift requires preparing alegal instrument such as a will or conveyance, however, the client should have the detached advice that another lawyer can provide." Id. 160. See, e.g., Magee v. State Bar of California, 374 P.2d 807 (Cal. 1962) (stating that "[tlhe highest good faith an attorney owcs his client requires the attorney to rebut the inference of undue influence that arises when he receives a gift from the client under circumstances that reasonably suggest such influence"). A more complete legal analysis is presented in infra Part N. 161. 793 P.2d 479 (Cal. 1990). 162. Id at 48 1. 163. Id

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therapeutic value, and the Regents applied for a patent on the cell line, listing the physician as one of the inventors.'" Moore filed suit asserting a variety of claims, including failure to obtain informed consent, breach of fiduciary duties, and a property right to share in the profits derived from the use of his cells.'65The Supreme Court upheld Moore's standing to bring the claim for breach of fiduciary duties and informed consent,'" but the court held that the property claims failed to state a claim upon which relief could be granted.'67 The majority stated that "an examination of the relevant policy considerations suggests an appropriate balance: Liability based upon existing disclosure obligations, rather than an unprecedented extension of the conversion theory, protects patients' rights of privacy and autonomy without unnecessarily hindering research."I6' Justice Mosk began a vigorous dissent by urging that the court look at the case in the context of "the recent explosive growth in the commercialization of biote~hnology."'~~ He stressed that courts are singularly competent to deal with such a common-law tort issue.'70 Justice Broussard, concurring-in-part and dissenting-in-part, pointed out that: Although the majority opinion . . . appears to suggest that a removed body part . . . may never constitute 'property' for purposes of a conversion action, there is no reason to think that the majority opinion actually intends to embrace such a broad or dubious proposition. If, for example, another medical center or drug company had stolen all of the cells in question from the UCLA Medical Center laboratory and had used them for its own benefit, there would be no question but that a cause of action for conversion would properly lie against the thief. . . . Thus, the majority's analysis cannot rest on the broad proposition that a removed body part is not property, but rather rests on the proposition that a patient retains no ownership interest in a body part once the body part has been removed. . . .I7'

effectively to abandon any property right in such materials; signing a consent form allowing researchers to study one's samples creates a defacto gift of all property rights in the samples as well. In theory, the individual research subject could bargain for an interest in products or discoveries made with his cells. However, in the real world the patient lacks the sufficient information and bargaining power proven to do so, especially in a pre-surgery situation. This means the patient has only two real choices: consent and have no control over subsequent use, or do not consent. The attempt to make the property entitlements clear in the Beth Israel informed consent form can be seen as a response to the California court's ruling. Specifying such property conveyances in the informed consent form not only satisfies Moore, but provides legal insurance in case the opposite default rule were to hold in other jurisdiction^.^ The informed consent form, however, is not an appropriate place for conveyances of property from patient to hospital. Although informed consent purports to protect the interests of the patient (subject) vis-A-vis the researcher, it often serves to protect the research institution more than the patient,'74 and shortcomings of informed consent in terms of voluntariness have been welldo~umented.'~' Historically, the legal fiction that subjects are making a free and autonomous choice is accepted as part of a greater understanding that the research will benefit them directly or indirectly by contributing to the advancement of b i 0 m e d i ~ i n e . IThe ~ ~ existing regulatory regime evinces a sort of social contract whereby subjects may sacrifice some autonomy in return for allowing research to proceed more efficiently. In theory, expert ethical oversight in the form ofthe IRB prevents any substantial injustice or malfeasance. However, as the informed consent form attempts to do more legal work, that is, effect transfers of material property rights, this delicate balance is endangered.

Most ofthe commentary on Moore has focused on whether individuals should have property interests in their bodily n ~ a t e r i a l s . 'Regardless ~~ of how this question is resolved, the ruling carries practical effects that are troubling: T o agree to participate in research through the use of one's tissue samples is -

164.Id at 481-82. 165. Id. at 482 n.4. 166.Id. at485,497. 167.Id. at 497. That is, the Court granted the defendant's demurrer on the conversion claim. Id.

168. Id. at 494. 169. Id. at 507. 170 Id - . -. -.

171. Id. at 501 (citation omitted). 172. See, e.g., BOYLE, supra note 6, at 99-101; E. RICHARD GOLD, BODYPARTS: PROPERTY RIGHTSAND THE OWNERSHIP OF HUMANBIOLOGICAL MATERIALS23-24 (1996); ALAN HYDE, BODIESOFLAW67-74 (1997);Jonathan Kahn, Biotechnology andthe Legal Constitution ofthe Se[j: ManaeineIdentin, in Science. the Market, andSocie@, 51 HASTMGSL.J . 909 (2000);Radhika Rao, " " Property. Privacy, and the Human Body, 80 B.U. L. REV.359 (2000).

210

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173. Such a default rule, that is, one that in the absence of an agreement otherwise grants property rights in human tissue to the donor rather than the researchers, would be, in my view, a stronger and more fair policy choice. Although strong arguments exist on both sides, and cannot be rehearsed here, one point consistently gets ignored and so deserves mention. Opponents ofapatient's default property rights often cite the trivial market value of removed tissue as a reason for the opposite rule. However, though the value of tissue or DNA may seem trivial to us now, there is no assurance that it will seem trivial in the future. Indeed, an individual's DNA and medical information may be worth more than we imagine already. See, e.g.,J.C. Bear, What Is a Person's DNA Worth? Fair Compensatronfor DNA Access, talk delivered at the 10th International Congress of Human Genetics in Vienna, May 200 1, available at http://www.mannvemd.is/englisWindex.html (last visited Ian. 26,2003). 174. Annas, supra note 42, at 2327. Consent forms "may be more likely to protect researchers and their institutions than research subjects." Id 175.See FADEN& BEAUCHAMP, supra note 2, at 274-97. 176. See id at 298-330.

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3. Rhetoric The BI informed consent form contains misrepresentations that hrther reduce its value as a vehicle for ensuring informed consent. The form states, "[ylou also understand and agree that the tissue you donate as a participant in this research program becomes the permanent property of the [hospital]."'" This terminology creates two problems. First, in most jurisdictions, bodily materials are not property, especially after the samples have left the body. People tend to think of their bodies as being above property, and courts and legislatures have expressed a profound discomfort with describing the body within the property di~course.'~' Conceiving of this material as traditional property, the form misleads the patient into believing that this question has somehow been settled. Second, the term "property" signals to donors that they retain fewer control rights than they actually do: I n imagining the meaning o f property, people call o n a particular set o f core conceptions, images, examples, and pictures o f the social world. Property is about ownership, and t h e core image o f ownership i s ownership o f a home. The core conception is the notion o f absolute control; ownership is the ability t o d o what you like with your own, without having t o account to anyone else for your

actions.'79 "Property" signals to patients that they have given up absolute control over the samples, when in fact research ethics requires giving people a right to withdraw from a study.Is0 The form also misleads patients by framing the project as a "research" study. This leads the patient to believe that research is occurring at the hospital. The top of the form signals that the form has been approved by the BI Committee on "clinical investigations."'" The protocol lists as "principal investigator" the chief of the hospital's department of pathology."2 Ardais is not mentioned until the third paragraph of the second page."' A careful reading of the form signals that Beth Israel is only in charge of "the collection" of samples and the transfer of Although the form property rights of use and access to Ardais C~rporation."~ presents a "research protocol," the patient is not agreeing to any specific "research," but granting permission for the "collection," transfer, and sale of 177. BI Informed Consent Form, supra note 157, at 4. 178. See GOLD,supra note 172, at 1-19. The body has traditionally been and continues to be valued in ways not normally associated with the market, for example, respect, dignity, community, and sharing. Id at 125-77. For further discussions of legal treatment of the body, see, for example, HY~E,supranote 172, at 48-79; Kahn, supra note 172, at 918-22; Rao, supra note 172, at365 n.15. 179. SINGER, supra note 137, at 29. 180. "[llf language supplied by one party is reasonably susceptible to two interpretations, one of which favors each party, the one that is less favorable to the party that supplied the language is CONTRACTS g: 7.1 1 (3d ed. 1999). preferred." E. ALLANFARNSWORTH, 181. BI Informed Consent Form, supra note 157, at 1. 182. Id. 183. Id. at 2. 184. Id. at 3 4 .

bioinformation to unforeseen researchers and research projects.''' The patient knows nothing about the range of possible genetic studies or the identities of thc researchers. Furthermore, the form attempts to trivialize the value of the property transfer by explaining that these samples "would otherwise be thrown away."186Tissue has long been stored and collected by pathologists because of its research value.187In an age when this material has developed significant markets and commodity status, this statement regarding the nature and the value of the patient's gift is particularly misleading. The form fails to offer an obvious alternative, that these samples could be held for research purposes without relinquishing patient rights. B17sclaims that the Ardais-BI relationship is somehow traditional and that misrepreholding equity stakes in for-profit tissue banks "is common pra~tice""~ sent the novelty of such a configuration. The statement that the hospital "may choose to own s t o ~ k " "misrepresents ~ the fact that the BI already owns a small equity share.Ig0 The consent form is misleading in stating that the donation of "property" is revocable. The form assures patients that "even if you now consent to the use of your tissue for research, you can change your mind at any time,"lgl but elsewhere it states that "[ilf you contact us and let us know that you do not want us to use your tissue, any remaining tissue still in the tissue bank will be discarded and will not be used for research."192This right to revoke does not apply to specimens already "licensed out" by Ardais.lg3 Furthermore, t h e form contains no provision to k e e p donors apprised o f the research uses to which their samples are put. To provide a right to withdraw without informing the donor about ongoing research is no better than demanding an irrevocable gift. As with the HSD Act, in order to encourage donation, the BI informed consent form conveys to the patient that she is involved in charitable endeavor. She is asked to "participate in this process" by which "many recent advances in medical research have been made by scientist^."'^^ The form invokes the existing social rhetoric that donating one's body to "science" is contributing to the common good. The false expectation created by such language is that the benefit 185. See id at I. 186. Id. at 1. 187. "The medical and scientific practice of storing human biological materials is more than 100 years old." BIOLOGICAL MATERIALS, supra note 10, at 1. 188. BI Informed Consent Form, supra note 157, at 3. 189. Id. 190. Schnitt interview, supra note 144. 19 1. BI Informed Consent Form, supra note 157, at 3. 192. Id. at 2. 193. Schnitt interview, supra note 144. Further, the form states that "in some instances, various components of the tissue such as DNA, RN, and proteins, may be extracted from the tissue for research use." BI Informed Consent Form, supra note 157, at 2. The form does not, however, givc patients a right to revoke cell lines or genetic information already derived from donated cells. 194. BI Informed Consent Form, supra note 157, at I .

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213

Winickoff

Governing Population Genomics I

of such a donation will inure only to the public and not the research institution or particular companies. In the commercial alliance of hospitals and Ardais, informed consent has become the mechanism through which hospitals may leverage their reputation with patients and access to bioinformation. But if it is Ardais that organizes and banks the tissue, why is it not asking for consent? The a?swer is obvious: people do not trust company officials the way they trust nurses and doctors. Patients are at their most vulnerable when in the hospital for imminent surgery. Further, patients associate the hospital with charitable purposes. In this way, a hospital informed consent process that calls for hospital nurses to present the form before surgery and invokes the language of participation in the biomedical research process leverages goodwill and trust to generate new kinds of revenue.

B. Legitimacy of the Ethical Oversight IRBs are the sole bodies in the regulatory system whose central purpose is the protection of research subjects. They have important responsibility in verifying that the human-subject protections are pr~vided.'~'Both Beth Israel and Ardais rely on this system to sustain their claim that in their collaboration, "patient protection is paramount" and that they "are dedicated to compliance with all existing federal, state and institutional requirements pertaining to the participation of patients in discovery research and the collection and use of clinical specimens and i n f ~ r m a t i o n . " 'However, ~~ this "clinical genomics" model raises serious concerns about the accountability and legitimacy of ethical review and illuminates important shortcomings in existing regulations. Two phases of ethical oversight will have occurred by the time a patient's bioinformation is used by an Ardais customer. First, the collection protocol at the hospital must pass through the hospital IRB approval process as mandated by the Common Rule.I9' Second, before Ardais will send off samples and medical information to other companies and researchers, the research protocols will be approved by an additional "independent" IRB that Ardais has hired.19' Both of these oversight structures entail problems of accountability, independence, and political legitimacy. The Beth Israel IRB has approved a "research protocol" that effectively removes the IRB from any review of the research that will occur. The Beth Israel IRB lacks the authority to oversee potential uses of the material once it has reached Ardais Corporation. Instead, the IRB ofArdais or ofArdais's clients will

195. Institutional Review Boards. A Time for Reform: Hearing Before the Committee on Government Reform and Oversight, Subcommittee on Human Resources, 105th Cong. (1998) (testimony of George Grob, Deputy Inspector General for Evaluation and Inspections, DHHS), available at LEXIS, Federal Document Clearing House Congressional Hearings Summaries. See also BROWN, supra note 26; BROWN, supra note 35. 196. ARDAIS, supra note 155. 197. 45 C.F.R. $6 46,109-,111 (2002). 198. Schnitt interview, supra note 144.

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be vested with the ethical oversight of particular projects. Thus, Ardais's IRB becomes the only body reviewing the research to ensure that patient interests are protected. The BI IRB has not actually approved the risks and benefits ratio of any particular research, but rather the risks and benefits of inclusion in a commercial tissue bank for any subsequent "research" use.Ig9This goes against even the more lax opinions regarding acceptable "open consent."2w "Research" is a broad and ill-defined category that includes everything from human cloning experiments to disease linkage studies. The BI IRB makes no attempt to inform subjects about the nature of particular research uses, and the Ardais IRB has no way of contacting donors because the samples are coded at the hospital.201This places the research protocols beyond any possible oversight of the patients or their hospital. Beth Israel's delegation of oversight for future research is an abdication of responsibility and accountability to its patients. Its approval of this collection project, which actually involves no research but rather the commercial transfer of tissue samples and medical information, raises crucial questions about whether the "affiliated" IRB has enough independence from the financial and research interests of its home institution to be a legitimate and effective source of review. These problems underscore the need for greater and more direct representation of the patient or donor group on affiliated IRBs. Meaningful oversight of research must come from the IRB that Ardais hires, and this IRB will face inherent conflicts of interest."' IRB members are likely to have a collegial relationship with researchers at the institution, or they may be researchers themselves. To some extent, this inherent conflict of interest is unavoidable. However, the conflicts are obviously greater when, as is the case in the BI-Ardais collaboration, the IRB hired by Ardais holds a direct financial interest in seeing the research come to fruition. Ardais' use of an "independent" IRB raises other well known problems. In a recent report, the Department of Health and Human Services noted both advantages and disadvantages to the emergence of independent IRBs.'"' While independent IRBs are geared to make quick decisions and can provide detached expertise, they are subject to market pressures that heighten conflicts of interest with the core mission of protecting research ~ubjects.~"In addition, they heighten concerns about IRB shopping. Independent IRBs, like institution-affiliated IRBs, may be under pressure to favor the interests of their institutional contractor^.'^^

199. BI Informed Consent Form, supra note 157, at 1. 200. BIOLDGICALMATERIALS, supra note 10, at 64-65. 201. Schnitt interview, supra note 144. 202. See, e.g.,George J. Annas, Ethics Committees: From Ethical Comfort to Ethical Cover, 21 HASTNGSCTR.REP., May-June 1991, at 18, 19; NBAC, supra note 2, at 61. supra note 26, at iii. 203. BROWN, 204. Id. 205. NBAC, supra note 2, at 61.


C. Allocation of Commercial Benefits The BI consent form states that "there will be no direct benefit" to participants in the program, but that "society may benefit fiom research using your tissue by learning more about what causes diseases, how to prevent them, how to treat them, and how to cure them."z06 To support this refusal to iwlude patients as recipients of the financial returns, one might argue that because benefits of the research will accrue to society in the forms of scientific progress, therapies, and drugs, additional compensation of patients is unnecessary. The contribution of tissue costs the patient nothing, whereas the contribution of researchers-like labor, capital, and inventiveness-is more deserving of reward.'07 This reasoning is certainly familiar, but it likely overstates the contributions of researchers in relation to those of tissue sources.208Further, who is really benefiting fiom this "altruism," and by how much? Hospitals are able to generate rents from these materials, and the commercial value of companies like Ardais consists almost exclusively in their control over this tissue and medical information. There is no denying that the private sector brings important therapies to patients, but considering the increasingly important role that this material plays in the world of commercial genomics, is this "trickle-down" approach sufficient and equitable consideration for the provision of such an indispensable input? Should the hospital do nothing to ensure that the commercial value generated by the research protocol at least inures to the community of patients directly? The answers to these questions implicate politically contestable views about the role of the private sector in distributing health benefits to society. Some would argue that it is justifiable for hospitals to use access to patients and medical records to appropriate and transfer their commercial value without benefitting the donor group directly. Tissue and medical records become a means for health institutions to generate revenue in hard economic times, permitting their doors to remain open for patient care. In addition, minimizing development costs encourages investment and innovation. But another perspective suggests that the system uses the trust inherent in the health care setting to help induce gifts, unfairly allocating benefits. This view questions the assumption that individuals should transfer resources to the private sector without negotiation. It might emphasize the larger-than-usual profits generated by the pharmaceutical industry, as well as the subsidies granted by the

206. BI Informed Consent Form, supra note 157, at 3. GENETICS 240,242 (2001). 207. See K. Berg, The Ethics ofBenefit Sharing, 59 CLINICAL supra note 6, at 97-108 (arguing that prevalent legal concepts of intellectual 208. See BOYLE, property, including those expressed by the Moore majority, reflect a misplaced notion of authorship and a labor theory of value that undervalues the contribution of sources vis-a-vis "inventors"). See also, Mary Taylor Danforth, Cells, Sales, and Royalties: The Patient's Right to a Portion ofthe Profits, 6 YALEL. & POL'Y REV.179,201 (1988) (arguing that a profit sharing arrangement would fairly compensate the contributor of tissue).

216

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tax ~ y s t e m . " This ~ view recognizes that Ardais Corporation and its customers have no legal duty to benefit the public, but rather a duty to turn profit for shareholders. Under an "equity theory" of distributive justice, each person who contributes to a collective enterprise deserves a reward commensurate with the magnitude of his or her contribution to the enterprise.'I0 The theory meets a potential practical problem here, for each person's contribution is too small to make compensation of each individual efficient. But this is simply a restatement of a collective action The final problem: collectively patients' contributions are quite signifi~ant.~" section of this paper presents a proposal that would address the "collective action" impediment to upholding an equitable distribution of benefit.

V. FOUR AVENUES FOR REFORM A. Litigation

1. International Human Rights Law Current litigation in Iceland might provide a good opportunity for the implementation of more rigorous informed consent requirements into international human rights law. commentators are divided as to whether the "presumed consent" structure implemented by the HSD Act is legal under Icelandic and international Challenge has been brought under a combination of Article 7 1 of the Icelandic Constitution, which deals with privacy:" European Directive 95/46/EC dealing with Data P r o t e c t i ~ n ?Article '~ 8 of the European Convention for the Protection of Human Rights and Fundamental freedom^,"^ and Chapter I1 ofthe Council of Europe's Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medi~ine.~'~

209. Marcia Angell, Editorial, The PharmaceuticalIndust~ToWhomIs It Accountable, 342 NEWENG.J MED. 1902, 1904 (2000). SOCIALPI~ILOSOPHY 1 14-16 (1973). 2 10. See, e.g.,JOEL FENBERG, 2 11. MANCUROLSON, THELOGIC OF COLLECTIVE ACTION(2d ed. 1971 ). 212. Compare Henriette D.C. Roscarn Abbing, Central Health Database in Iceland and Patient's Rights, 6 EUR.J. HEALTHL. 363 (1999); andGreely, supra note 105 (finding it illegal), with O.M. Amard6ttir et al., The Icelandic Health Sector Database, 6 EUR.J. HEALTHL. 307 (1999), and Hr6bjartur J6natansson, Iceland's Health Sector Database: A Sign$cant Head Start in the Search for the Biological Grail or an Irreversible Error?, 26 AM.J.L. & MED.3 1 (2000) (finding it legal). 213. The relevant IanguageofArticle 71, in translation is: "Everyone shall enjoy freedom from interferencewith privacy, home, and family life." See http://government.is/interpro/s~r/stjr.nsf/pages/ icelandic-constitution.html. 214. Council Directive95/46/EC, 19950.J.(L281)3l, availableathttp://europa.eu.int/comrn/ internal-market/en/dataprot/law (last visited Jan. 26,2003). 21 5. ETS No.: 005, available at http:Nconventions.coe.int~Treaty/EN/CadreListeTraites.htrn (last visited Jan. 20,2003). 216. ETS No.: 164, available at http://conventions.coe.intlTreatylENICadreListeTraites.htm (last visited Jan. 20, 2003).

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Governing Populatiotz Genomics

It is unclear if there is a right to affirmative informed consent for bioinformatics research in Iceland, and it is even more unclear if some sort of universal right exists that could trump a majority vote. Biotechnology is an area where the temptations of privileging communal pressures over the individual are especially a ~ u t e . ~Nonetheless, " because of the imperfections of democracies, most liberal theorists would argue that the presumption must be in favor of protecting the individual. Even some of the strongest advocates of group rights would agree.21s This might be called a "supplemental" approach to minority rights, and it would support, for example, the need to obtain informed consent from individuals on top of group consent. In cases where the group rights are being asserted not by an ethnocultural minority, but by the state, the case for the supplemental approach is even more compelling.

2. American Common Law One place to reform the common law would be to depart from Moore, either by adopting the lower court's theory of appropriation of identity,2I9 or by permitting a cause of action for conversion. The BI consent form raises a set of similar problems, and it is informative to consider how these transactions might be challenged. a. Enforcing the Agreement Most likely, the conveyance of "property" called for in the informed consent form is a revocable gift. The donor may withdraw from participation in the research at any time.'" The ability to opt out at any time is a fundamental component of the informed consent procedures required by the Common Rule.221 Therefore, patients could ask to withdraw their consent from the project. If the hospital refused to withdraw all samples from all research, they could sue for injunctive relief. Because any ambiguity will be construed against the drafter,222 and especially because the drafter in this situation is in a more powerful position, if a fair interpretation admits a full right to withdraw, then the patients should prevail.

in

217.See,e.g.,Sirkku Kristiina Hellsten, Biolechnology. Genericlnformation, andcommunily, GENETIC INFORMATION, supra note 14, at 297,305. 2 18. WILLKYMLICKA.POLITICSIN THE VERNACULAR: NATIONALISM, MULTICULTURALISM AND

CITIZENSHIP 22 (2001). 219. A theorv. esooused by Professor Jonathan Kahn. See Kahn, supra note 172, at 91G11. . 220. BI Informed Consent Form, supra note 157, at 3. 22 1. 45 C.F.R. 8 46.1 16(a)(8)(2002). 222. See supra note 180;see also RESTATEMENT (SECOND) OF CONTRACTS 8 206 (1993). This supra note 180. rule is favored particularly in the context ofstandard form contracts. FARNSWORTH,

b. Voiding the Agreement The rule that "the subject may discontinue participation at any time"22' derives directly from the Nuremberg Code.224This requirement should create a presumption that any ambiguous withdrawal language is intended to confer an absolute right to revoke permission. Moreover, even if the court interpreted the language otherwise, the patients could argue that this is not a valid informed consent under the regulations. Consent could also be nullified on the basis of another Common Rule requirement, namely that "[nlo informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights."22sThe BI consent form certainly appears to waive particular property rights that patients have in their materials before extraction, for example, the right to use, possess, transfer, and exclude others.226As Justice Broussard makes clear in Moore, this is the crucial point that the Moore majority seemed to ignore.'" A third means of vitiating the consent is an "undue influence" theory. The concept of undue influence developed to give equity to victims of transactions induced by improper persuasion, especially to gratuitous transfers.228Courts have voided gratuitous transfers when two elements are present: "a special relation between the parties" and "improper persuasion of the weaker by the stronger."229 A finding of unfair persuasion generally relies on a variety of factors, including unfairness of the resulting bargain, unavailability of independent advice, the lack of time for reflection, and the susceptibility of the weaker party.230Courts often state that once the requisite relationship is found, a presumption of undue influence is establi~hed.~" Here, the relationship between the patient and the doctor falls into the classic category of a special relationship, and most, if not all, of the factors that establish undue influence are satisfied. The hospital patient, especially one who, for example, has cancer and will undergo surgery the following day, is a classic example of a weak party with no outside advice and with little time for reflection.

223.45 C.F.R. 5 46.116(a)(8). 224. NUREMBERG CODE, supra note 20. 225.45 C.F.R. 8 46.1 16. 226. Rao,supra note 172, at 371 ("[H]unian bodies and parts are currently treated as property in many contexts. Blood and sperm are regarded as products that may be purchased and sold. . . .") 227. Moore v. Regents of the University of California, 793 P.2d 479, 501 (Cal. 1990) (Broussard, I., concurring-in-part, and dissenting-in-part). 228. FARNSWORTH, supra note 180, at 6 4.20. 229. Id. Classic examples of special relations are parent and child, clergy member and communicant, husband and wife, or physician and patient. It has also been extended "beyond relations characterized by trust and confidence to those in which the weaker party is for some reason under the domination of the stronger." Id. 230. Id. 231. Id,; see,

e.g., McCollough v. Rogers, 431 So. 2d 1246 (Ala. 1983) (holding that a confidential relationship raises a presumption of undue influence).

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c. Remedies

information generated by such research"240 and to "negotiate the terms and conditions of a research agreement and submit such agreement for execution by the Tribal C ~ u n c i l . " ~ ~ ' The IRPA stresses the importance of process and negotiation. It notes that "tribal members have been the subjects of research for decades, with virtually no benefits returning back to the community from the research."242As a result, the IRPA includes a list of principles that the Research Review Committee will seek to uphold,243including ( I ) "fully informed consent," which includes disclosure of "all relevant affiliations of the person(s) or organization(s) seeking to undertake the research, and all sponsors of the researcher(^),"^^^ (2) "immediate benefits to the tribal community,"24s and (3) submission of a research proposal before any research will be approved.246Specifically, this report must:

If the initial agreement were void, a possible remedy would be an equitable injunction to stop the research and to compel the return or cbstruction of the samples. Equitable relief is available to cancel a conveyance of property rights,232 and this remedy would be consistent with the origins of the undue influence doctrine in equity.233The parties could, and in all likelihood would, negotiate an agreement for financial benefits.

B. Political Organization and Community Development In response to the HGDP, several indigenous groups led by the Indigenous Peoples Council on Biocolonialism (IPCB) created alternative visions for the protection of native group autonomy. The IPCB created the model Indigenous Research Protection Act (IRPA) to address the fundamental issue of control in the design, implementation, and oversight of genetics research.234The IRPA aims to ensure that "indigenous groups are asserting their own rights to take proactive measures to protect themselves and their territories by controlling re~earch,"~" and it establishes a model for indigenous groups to create their own oversight process and assert property rights over genetic resources.236The IRPA

demonstrate how the participants and the Tribe will be given a fair and appropriate return for cooperation in the research. Just compensation or fair return includes but is not limited to: obtaining copies of the research findings, authorship, co-authorship or acknowledgment, royalties, fair monetary compensation,copyright, patent, trademark, compensation for expenses incurred in reviewindadvising researchers, coverage of trainindeducation or outreach expenses or other forms of compensation.247 The IRPA specifies that "[wlhere any of the products of the research are to be used for commercial purposes, a separate agreement will be made specifying the bases on which sales are to be made and the proceeds of sales are to be distrib~ted."~~' This "negotiated model" ofequitable benefits helps ensure that the principles of autonomy, justice, and beneficence are more closely adhered to, and it puts the burden on the research institution to begin thinking about these principles before it contacts the potential donors. Nevertheless, there are three potential drawbacks to such a strategy. First, this type of strategy may only work with small, easily identifiable groups. Community input and participation in the design, implementation, and oversight of protections will be much more difficult if no political structure or community review board exists. However, if the subject population will be drawn from the same health clinic or hospital, then a body of patient community members might form the "group" and seek legal counsel. Second, political activists may run into many of the problems of group self-determination that limit the autonomy of groups and their individuals. Third, even if such political organizing were to be successful, the groups are in the position ofwaiting

helps tribal governments protect their people against unwanted research and when they believe the research may be beneficial the IRPA provides a framework to control the research agenda. This changes the paradigm from being treated as research subjects to being active partners with the power to make informed decisions and choices. It is believed that more tribal control of research is likely to result in more beneficial outcomes, and of the research actually meeting the needs of the people.237

The act, which establishes a model of governance for all research occurring on tribal lands, establishes a Research Review Committee with broad powers238 made up of five tribal members appointed by the tribe's governing body.239The Committee has the responsibility to coordinate and interact with the researchers to "ensure Tribal control of the research process and Tribal ownership of data and

232. In Massachusetts, and other jurisdictions, contract law clearly permits such an equitable remedy. See, e g . , Keville v. McKeever, 675 N.E.2d 417, 424 (Mass. App. Ct. 1997) (denying plaintiffs right to a jury trial for claims under undue influence theory because these claims were

deemed to be "within the court's equity jurisdiction"). 233. FARNSWORTH, supra note 180,$4.20. 234. INDIGENOUSRESEARCH PROTECTION ACT,available at http://www.ipcb.orglpublications/

240. Id. 5 4.2(e). 241. Id. jj 4,2(f). 242. Id $ 1.4. 243. Id. $5.1. 244. Id. jj 5.l(a). 245. Id. 4 5.l(b). 246. Id $ 6.2. 247. Id jj 6.2(i). 248. Id Q: 8.2.

policy/index.html (last visited Jan. 20, 2003) [hereinafter IRPA]. 235. Debra Harry, Biopiracy and Globalization: Indigenous Peoples Face a New Wave of Colonialism, Comments for the International Forum on Globalization Teach-in held in New York City in February 2001 (on file with author). 236. Id. 237. Id. (emphasis added). 238. IRPA, supra note 234, jj 4. 239.Id $4.1.

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1

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Winickoff for opportunities to arise instead of creating uses for their bodily7naterials that they deem beneficial.

C. The Tissue Trust Beyond organizing to bargain with research institutions, people might want to organize to collect the biological materials themselves. A dissenting opinion in Moore contained such an idea: "[Ilt would be wiser to . . . require all valuable excised body parts to be deposited in a public repository which would make materials freely available to all scientists for the betterment of society as a The construction of a nonprofit trust might be a better model for the management of biological samples, genetic information, and medical records.2s0 It might also provide a viable "middle course" between regimes oftissue donation The following is a preliminary sketch of such a tissue and full marketizati~n.~~' management structure. A trust involves a fiduciary relationship in which trustees hold title to property but have an obligation to keep or use the title for the benefit of the benefi~iary.'~' Fiduciary responsibilities would help ensure that patients' or donors' interests were upheld. Before a biopsy, patients would be presented with a form of contractual permission for the gift of their bodily material and medical information. The permission form would make it clear both that participation in the trust would be optional, and that tissue not needed for their clinical testing would be destroyed if they so chose. All scientists seeking to use the tissue would have to propose the specific project both to an IRB and the trust's ethics committee, which would contain direct representatives of the donors. The trustees would negotiate shared intellectual property arrangements with the researchers so that a portion of profits derived from the material would finance the operation of the trust and provide a charitable health fund. The trustees would decide how to disburse this fund. Further, the trustees would have a duty to keep donors informed about particular research projects, and there would be a possibility for the public hearing of concerns about particular studies. Something akin to this tissue trust model has already emerged in practice. Disease groups have begun to construct their own tissue banks as a way to control

research design, implementation, and benefit. Pseudoxanthoma Elasticum (PXE) is a rare, hereditary connective tissue disorder that afflicts the skin and eyes.2s3 PXE International is a lay volunteer nonprofit foundation that has collected tissues and controls a tissue bank containing blood, isolated DNA, skin, and organs from over 1000 individuals affected by PXE.254The foundation also collects clinical data, medical information, and pedigree diagrams from affected individuals. The goal of the organization is simple: to get researchers to study the genetic basis of PXE to develop therapies.'" PXE International has its own informed consent form for the collection of blood, tissue, and health information. The form states that research will be done "to help us and other researchers understand PXE."256This simple form explains that the tissue will be banked and loaned out for research projects approved by the PXE International research committee.2s7 Subject to an intellectual property agreement, researchers can use the samples and information in an anonymized form, that is, with code numbers instead of names.2s8Participants will not be contacted about the results of any research "unless it appears likely that the results of a study contain critical information for personal health care."259 Finally, patients can withdraw at any time.260 Any research using the PXE tissue must get its own IRB approval. However, PXE International has its own "ethics committee" with representatives from the donor group who must also approve the research before access to the samples is granted. Furthermore, PXE does not keep information about ongoing research projects out of the hands of participants. When they apply to PXE for access to the tissue, researchers must submit a one-page description of the project for inclusion in a PXE International Newsletter that is sent to all participants. Although there are no direct financial benefits to tissue donors, the PXE model more appropriately addresses the needs and concerns of patients. The potential benefits to the group are tailored to the specific research, about which the participants are continually inf~rmed.'~' PXE International communicates with its collaborating research groups as often as eight times each week, and direction of the research is accomplished by working closely with the research labs themselves.262Specific terms of a research 253. CANCERWEB,

ON-LMEMEDICALDICTIONARY(12 Dec. 1998), http://cancerweb.

ncl.ac.uWcgi-bin/omd?PXE(last visited Feb. 4, 2003).

249. Moore v. Regents of the University of California, 793 P.2d 479, 505 (Cal. 1990) (Broussard, I., concurring-in-part and dissenting-in-part). 250. Karen Gottlieb, Human Biological Samples and the Laws of Proper@: The Trust as a supra note 17, at 182, 192-95. Model for Biological Repositories, in STOREDTISSUE SAMPLES, 25 1. See, e.g., Charlotte H . Harrison, Neither Moore nor the Market: Alternative Models for Comoematina Contributors ofHuman Tissue, 28 AM.J.L. & MED. 77,78, 104 (2002) (arguing that the apparent &econcilabilityofthe positions of advocates and opponents ofproperty rights in human tissue reauires consideration of alternative legal structures within which to allocate the financial rewards generated by the use of patient tissue). T. BOGERT, TRUSTS 8 1 (6th ed. 1987) 252. GEORGE

254. PXE International, Inc., Blood and Tissue Bank Policy Guidelines (2000) (on file with author). 255. Telephone interview with Sharon Terry, President of PXE International, Inc. (Oct. 23, 2000). 256. PXE International, Inc., Consent Form for Participation in Tissue and Blood Donation (on file with author). 257. Id at 1. 258. Id. at 2. 259. Id. at I. 260. Id. 261. Interview with Sharon Terry, supra note 255. 262. Id

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collaboration are stipulated in written agreement^.'^' The policy for the transfer of materials states that "any products of the blood and tissue of PXE Iniernational are considered to be the shared property of PXE International and the research laboratory."264 Further, any patents, profits, and revenues therefrom must be shared with PXE International according to agreements made at the time of the ~~ these restrictions on the commercial right of patent a p p l i c a t i ~ n . 'Considering researchers to the tissue, one might speculate that PXE International would continue to have trouble attracting researchers. However, PXE International has been extremely successful at attracting collaborating research groups, and there Satellite tissue banks are now 17 laboratories in the PXE research con~ortiurn.'~~ are being built in several other countries.267 A big problem for rare-disease groups has traditionally been the failure to attract researchers to study the di~ease.'~'Commercial researchers fail to invest in these "orphan diseases" because the potential market for diagnostics, pharmaceuticals, and therapies is too small to justify the vast expenditures needed to bring them to market.269Accordingly, the motivation of PXE International is to attract researchers to the disease.270The PXE strategy uses the economic value of the tissues and the organization's control over them both to further particular research goals important to the community and to correct market failure^.'^' Most of all, the PXE patient group wants to facilitate the discovery of a therapeutic intervention to help their families and future patient^.'^' The terms of their participation are very clear: You will not get financially rewarded, but this is the best chance to help cure the disease.273 PXE has already seen success from this strategy. In October 2000, Nature announced the imminent filing of a patent application for a gene causing PXE.274 This imminent filing listed two "coinventors": the researchers who isolated the gene and the patient advocacy group that helped make the discovery possible.

263. Id. 264. Blood and Tissue Bank Policy Guidelines, supra note 254, at 1 265. Id. 266. Interview with Sharon Terry, note 255. . supra . 267. Id. 268. See, e.g.,Lars Noah, The Coming Pharmacogenomics Revolution: Tailoring Drugs to Fit J . 1, 16-17 (2002). Patients ' Genetic Profiles, 43 JURIMETRICS 269. See id. However, the Orphan Drug Act, enacted in 1983, sought to remedy this problem. Pub. L. No. 97-414, 96 Stat. 2049 (codified as amended at 21 U.S.C. 58 360aa-360ee (2000)). It provides tax breaks, federal grants, and extended market exclusivity for companies developing drugs for the treatment of rare diseases. Noah, supra note 268, at 16; see 21 U.S.C. $8 360cc, 360ee; 26 U.S.C. g: 4SC (2000). 270. Interview with Sharon Terry, supra note 255. 27 1. Id. 272. Id. 273. Id. 274. Paul Smaglik, Tissue Donors Use Their Influence in Deal Over Gene Patent Terms, 407 NATURE82 1, 82 1 (2000).

224

4 3 JURIMETRICS

This "novel alliance could become a model for handling intellectual property emerging from collaborations between patients' groups and researcher^."^" Both the charitable tissue trust model and the PXE International model hold particular advantages over existing commercial projects in terms of bio-autonomy, political representation, and equitable benefit. The key advantage lies in the way in which donors use the economic and research value of their biological samples to pursue particular preferences and goals. One of these goals is to ensure that bio-autonomy is promoted through rigorous informed consent processes, continuous updates on existing research projects, and an absolute right to withdraw from research. In addition, research cannot proceed without ratification of the project by a body directly representing the interests of donors. In this way, the PXE model or a trust model is similar to the system created by the Indigenous Research Protection Act. Instead of waiting for interested researchers to contact the group, the tissue trust allows donors to create research projects that they deem to be beneficial. This, in turn, increases their economic bargaining power with the research entities involved. This bargaining power leads to a number of important social benefits. First, research participants can use their bargaining power to direct research towards diseases that are currently neglected by the market. With negotiating power, donors of biological information could demand a greater amount of direct participation or representation in the ethical review and implementation of research protocols. Research subjects could also help ensure that research is conducted under just and politically acceptable procedures. They could require that oversight and information is provided for them after "open consent" is granted, ensuring that a right to withdrawal remains meaningful. The promotion of community empowerment vis-A-vis biosamples could help ensure that certain of these principles are implemented, especially "fair subject selection" and "respect for enrolled subjects."276 Volunteers could use their bargaining power to influence specific policies of research institutions.277For example, with more bargaining power and more meaningful choices, volunteers could support research institutions whose efforts are directed towards public health benefits instead of a purely market-driven research agenda. Critiques of the biotechnology industry have pointed out problems with "access" and "cost" of the very drug therapies that the commercial solicitors of 275. Id. 276. Ezekiel J. Emanuel et al., What MakesClinicalResearch Ethical?, 283 JAh4A 2701,2704, 2707 (2000). The authors define "fair subject selection" as the principle that scientific objectives, not vulnerability orprivilege, and the potential for and distribution ofrisks and benefits should determine communities selected as study sites and the inclusion criteria for individual subjects. Id at 2704-05 They define "respect for enrolled subjects" as requiring that subjects should have protection of their privacy, the opportunity to withdraw, and monitoring of their well-being. Id at 2707. 277. For example, volunteers could bargain for the sharing of research materials, the provision of direct benefits to participants, and ethical practices.

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Governing Population Genomic~

bioinformation promise consumer^."^ Donors might favor research institutions that promise some sort of compensation for donors in the form of access to therapies or even remuneration where donation leads to large profits. ponors might wish to weigh in on contested issues, such as health care resource allocation or patenting and commercialization of particular genetic sequences; to insure that their donation serves the public good and not narrow commercial interests. Finally, donors may wish to refuse con~ent."~ The main drawbacks to a trust system are practical. First, it would require significant initial investment. Second, without a government mandate, it is unlikely that many of these organizations would emerge. In the IRPA and PXE cases, the pre-existence of both strong community identity and common goals generated meaningful political representation and bargaining power.280As we move from pre-existing volunteer groups with existing organizational structures to larger, more heterogeneous and more dispersed volunteer groups, these models of representation may be of less value. In these cases, without some sort of restructuring, nobody other than the federally mandated IRB would protect the interests of patients and donors.

D. Regulatory Approaches: Reforming the IRB Although reforming the common law and building grass roots support for change are important, particular reforms of the existing regulatory structure are clearly required. Existing recommendations would bring improvements to the oversight of genomics and other research, but they are not specific enough to ensure that the foundational principles of autonomy, justice, and beneficence are upheld. The HGDP and Ardais case studies suggest how biobanking for commercial genomics research needs to recognize a shift from an elite or expert model to one that is more equitable, democratic, accountable, and transparent. The Iceland case study demonstrates, however, the continued need for independent expert analysis to guide understanding in the face of increasing technical complexity. Accordingly, the best reform strategy would have to make IRBs more independent from commercial institutions and more representative of patients' interests while retaining a robust, though weakened, role for experts. The following proposals are

278. See, e.g., Angell, supra note 209. 279. For instance, if they found out that a company were conducting drug trials abroad in order to avoid more rigorous regulations. This practice is increasing at an alarming rate. A recent NBAC report calls for a range of changes in the conduct of research in developing countries to ensure that participants are adequately protected and to add safeguards in the way U.S. researchers and sponsors conduct clinical trials in developing countries. National Bioethics Advisory Commission, Ethicaland Policy Issues in International Research: Clinical Trials in Developing Countries (200 I), available at http:Nw.georgetown.edu/research/nrcbl/nbac/clinical/execsum.html(executive summary) (last visited Jan. 20,2003). 280. See supra Part 1V.B-C.

43 JURIMETRICS

meant to be a starting point for a discussion of specific changes in the IRB structure that may better ensure the adherence to principles.

I

1 . Development of a Nongovernmental Network of Independent IRBs It is widely argued that the IRB system sorely needs an accreditation pro~ess,'~' and this could be implemented through aNongovernmental Accreditation Organization (NAO)."' The NAO should not only accredit independent IRBs, but it should also administer a network of accredited independent IRBs.'~' When a research institution wants to go forward with commercial human subjects research, it should be required to give a written proposal to the NAO, similar to what the IRPA requires. Then the NAO would assign an independent IRB. The research institution would pay the NAO, not the IRB, and all IRBs would be paid similar rates for similar services. This plan would circumvent well-known problems of cronyism and conflict of interest with affiliated IRBs, and it would avoid well known problems of "market pressure" and "shopping" with IRBs."~

2 . Substantive Standards

i

Ij

i

As the case studies show, there is a dearth of guidance for ethical boards making decisions about genomics research. The NAO and the IRBs should have clear standards. In particular, the IRBs should have less discretion to waive informed consent requirements. Presumed consent is never acceptable for banking samples or medical data in commercial context. Informed consent cannot be waived, even for anonymous samples or anonymized medical records. Informed consent procedural standards should require that health professionals do not administer the informed consent for commercial biobanking in the therapeutic context. Thus, the informed consent process must be "adequately removed" from the therapy. Informed consent forms should never waive property rights of volunteers. Instead, conveyance of rights to commercial use should be effected through some sort of contract and done outside the context of clinical care. Research institutions should be mandated to provide informational updates to research participants when "open consent" has been granted as a means to effect a more meaninghl right to ~ithdraw.'~'

28 1. INST. OF MED.,supra note 40, at 1-2. 282. Id 283. This accreditation proposal dovetails with that of the Institute of Medicine. Id. at 2 4 . 284. "IRB shopping" is the attempt by researchers to select particular lRBs known to be more lenient, and it has been cited by DHHS as an emerging and significant concern. See BROW, supra note 26, at iii. 285. Others have also recommended this. E g . , George Annas, supra note 107, at 1832 (recommending that in the Iceland context, a meaningful right to withdraw would require Decode to keep the group ofresearch participants informed about its research agenda through mailings and a newsletter).

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Representation of the donor group within the IRB process needs to be overhauled. The IRB should obtain approval from a patient or donor group through a review committee, such as the IRPA "Research Review Committee" or the PXE "ethics commidee," if such a review board exists. These committees should include an attorney, and they could negotiate a commercial agreement where appropriate. In addition, more members of the IRB should be either members of the patient group or direct representatives of the group with fiduciary legal duties.

U.S. common law, administrative regulations, and international law attempt to uphold the traditional norms of biomedical ethics-respect for autonomy, justice, and beneficence-in the face of technological and societal change. However, the existing regulatory regime and its reformers have insufficiently addressed the issues of power and political process raised by genetics research on human populations. The case studies discussed have illuminated three particularly troubling areas: informed consent rules, expert ethical oversight, and allocations commercial benefits. First, innovations in informed consent have limited the capacity of individuals to make meaningful choices about the control of their bioinformation. Second, problems ofrepresentation, accountability, and conflicts of interest have undermined the political legitimacy of ethical review boards. Third, the prospect of commercial benefits and the commodification of bioinformation have complicated traditional bioethical risk-benefit analysis by introducing resource allocation decisions that are politically charged. Problems in the genomics area have also highlighted more general problems with existing systems of research oversight, most significantly the inadequacy of governance structures in terms ofrepresentation, participation, and accountability. In the face ofnovelty, principles ofautonomy, justice, and beneficence are being reconstructed innarrow ways by institutions with particular commercial and research interests. Governing population genomics requires a bioethics that takes the political power of participants more seriously. Accordingly, four avenues ofreform should be pursued. These reforms would help reestablish, at the cusp of the bioinformatics revolution, the trust between patients and doctors as well as research volunteers and researchers. Ultimately, it is in the interest of all researchers, biotechnology companies, and hospitals-indeed society as a whole-to preserve this trust. The quality of medical care depends on the free flow of information between patient and doctor. The loss of agency and control of bioinformation generated in genomics settings could alienate patients and make them reluctant to disclose information. Similarly, biomedical research of all kinds depends on the consent of research participants. The mere appearance of injustice and impropriety will jeopardize the very participation that makes research possible.

BUT-FOR MARKETS AND REASONABLE ROYALTIES: THE RZTE-HITE v. KELLEY MISDIRECTION Clement G . Krouse* ABSTRACT: U.S. patent law distinguishes between lost profit and reasonable royalty awards in infringement damage claims. Lost profits are calculated as a monetary damage; reasonable royalties are not. This is a false division. Only a reasonable royalty also calculated as a monetary damage is proper in the sense that it does not provide the patent holder with more than it would have earned had the infringement not occurred. Correspondingly, only an award of monetary damages accurately disgorges the infringer of the value gained from the illegal use of the patented technology. CITATION: Clement G. Krouse, But-For Markets and Reasonable Royalties: The RiteHite v. Kelley Misdirection, 43 Jurimetrics J. 229-241 (2003). The theory of damages underlying U.S. patent infringement law is selfcontradictory and inconsistent with economic principles. The origin of the theory and the apparent solution to its shortcomings can both be found in the Supreme Court opinion in Aro Manufacturing Co. v. Convertible Top Replacement Co.' The Court there began with the underlying statutory rule, which provides for a damage award "adequate to compensate for the infringement, but in no event less than a reasonable royalty for the use made of the invention by the infringer."' Relying on legislative intent, the Court specifically excluded damages in equity in its interpretation of "adequate to compensate."' The remedy was restricted to

*Clement G. Krouse is Professor of Economics, University of California, Santa Barbara 1. 377 U.S. 476 (1964). 2.35 U.S.C. 8 284 (2000). 3. 377 U.S. at 504-05.

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