Jahrbuch für Recht und Ethik / Annual Review of Law and Ethics: Bd. 9 (2001). Themenschwerpunkt: Schwierige Fälle der Gen-Ethik / Hard Cases in Genethics [1 ed.] 9783428505173, 9783428105175

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Jahrbuch für Recht und Ethik Annual Review of Law and Ethics Band 9 (2001) Herausgegeben von B. Sharon Byrd Joachim Hruschka Jan C. Joerden

Duncker & Humblot  · Berlin

Jahrbuch für Recht und Ethik Annual Review of Law and Ethics Band 9

Jahrbuch für Recht und Ethik Annual Review of Law and Ethics

Herausgegeben von B. Sharon B y r d · J o a c h i m H r u s c h k a * Jan C. J o e r d e n

Band 9

Duncker & H u m b l o t · Berlin

Jahrbuch für Recht und Ethik Annual Review of Law and Ethics Band 9 (2001)

Schwierige Fälle der Gen-Ethik H a r d Cases i n Genethics Herausgegeben von B. Sharon Byrd Joachim Hruschka Jan C. Joerden

Duncker & Humblot · Berlin

Die Deutsche Bibliothek - CIP-Einheitsaufnahme Jahrbuch für Recht und Ethik = Annual review of law and cthics. Berlin : Duncker und Humblot Erscheint jährl. - Aufnahme nach Bd. 2 (1994) ISSN 0944-4610 Bd. 9. Themenschwcrpunkt: Schwierige Fälle der Gen-Ethik. - 2001 Themenschwerpunkt: Schwierige Fälle der Gen-Ethik = Hard cases in genethics / Hrsg.: B. Sharon Byrd ... Berlin : Duncker und Humblot, 2001 (Jahrbuch für Recht und Ethik ; Bd. 9) ISBN 3-428-10517-6

Empfohlene Abkürzung: JRE Recommended Abbreviation: JRE Alle Rechte, auch die des auszugsweisen Nachdrucks, der fotomechanischen Wiedergabe und der Übersetzung, für sämtliche Beiträge vorbehalten @ 2001 Duncker & Humblot GmbH, Berlin Fremddatenübernahme: Berliner Buchdruckerei Union GmH, Berlin Druck: Color-Druck Dorfi GmbH, Berlin Printed in Germany ISSN 0944-4610 ISBN 3-428-10517-6

Vorwort Dieser Band des Jahrbuchs faßt die Beiträge zu einem Symposion zusammen, das die Herausgeber im Rahmen der Begleitforschung zu den rechtlichen, ethischen und gesellschaftlichen Implikationen des Deutschen Humangenomprojekts (DHGP) in der Zeit vom 31. März bis zum 4. April 1999 in Memphis, Tennessee, zu dem Thema „Hard Cases in Genethics" veranstaltet haben. An dem Symposion haben teilgenommen: Kurt Bayertz (Münster), Cornelia Bormann (Bonn), B. Sharon Byrd (Jena), Ellen Wright Clayton (Nashville), Lloyd R. Cohen (Arlington), Thomas Crofts (Perth), Ν. Ann Davis (Claremont), Andreas Drechsler (Bonn), Certi Dieker (Portola Valley), Roger B. Dworkin (Bloomington), Lawrence A. Frolik (Pittsburgh), Margaret G ruter (Portola Valley), Jan C. Heller (Seattle), David Heyd (Jerusalem), Joachim Hruschka (Erlangen), Jan C. Joerden (Frankfurt [Oder]), Eike-Henner W. Kluge (Victoria), Thomas Nenon (Memphis, Tennessee), Lorenz Schulz (Frankfurt am Main), Albrecht E. Sippel (Freiburg), Peter Stanglow (Frankfurt [Oder]), S. Edward Stevens, Jr. (Memphis, Tennessee), Gregory Stock (Los Angeles), Arnd Wasserloos (Frankfurt [Oder]), Erin Williams (Rockville), Richard M. Zaner (Nashville), Arnulf Zweig (New York). Die Veranstalter danken dem Bundesministerium für Bildung, Wissenschaft und Forschung (BMBF) und dem Deutschen Zentrum für Luft- und Raumfahrt (DLR) als Projektträger des Ministeriums für die Finanzierung des Symposions. Für vielfältige Unterstützung bei der Durchführung des Symposions in Memphis gebührt Prof. Dr. Thomas Nenon und Prof. Dr. S. Edward Stevens, Jr. (beide Memphis) herzlicher Dank. Für ihre Hilfe bei der Vorbereitung des Symposions und der Drucklegung dieses Bandes des Jahrbuchs danken die Herausgeber insbesondere Frau Anette Hübner im Interdisziplinären Zentrum für Ethik in Frankfurt (Oder) und Frau Ayke Darius im Institut für Strafrecht und Rechtsphilosophie in Erlangen. Herrn Lars Hartmann im Verlag Duncker & Humblot in Berlin ist für die verlagsmäßige Betreuung der Publikation zu danken. Die diesem Band angefügten Verzeichnisse haben Frau Cornelia Winter und Frau Anja Richter (beide Frankfurt [Oder]) erstellt, denen die Herausgeber dafür zu Dank verpflichtet sind. In seinem zehnten Band (2002) wird sich das Jahrbuch für Recht und Ethik schwerpunktmäßig dem Thema „Richtlinien für die Gentechnologie - Guidelines for Genetics" widmen. Das Jahrbuch für Recht und Ethik stellt im übrigen auf seiner Internetseite http://www.uni-erlangen.de/JRE im Hinblick auf die schon erschienenen und die projektierten Bände weitere Informationen zur Verfügung, insbesondere auch englische und deutsche Zusammenfassungen der Artikel sowie Bestellinformationen.

Inhaltsverzeichnis

Schutz und Gewinnung genetischer Information Protecting and Obtaining Genetic Information Roger Brownsword:

The Relaxin Opposition Revisited

3

Ellen Wright Clayton: Using Newborn Blood Samples for Genetics Research: Thinking About the Context 21 Lawrence A. Frolik/Margaret Testing

Gruter:

The Permissibility of Compulsory Genetic 33

Lorenz Schulz: Genetic Data Banks

43

Arnd Wasserloos : Whose Genes, Whose Ethics? Culture, Representation and Controversy in the Debates Surrounding the Human Genome Diversity Project 65 Erin D. Williams:

The Right to Obtain Genetic Information

Arnulf Zweig: Pragmatic Reflections in Privacy. "It's none of their business"

87 109

Nutzung genetischer Information - Using Genetic Information Kurt Bayertz : Pränatale Vaterschaftsdiagnostik und selektive Abtreibung. Ethische Überlegungen zu einem schwierigen Fall aus der genetischen Beratungspraxis 119 N. Ann Davis: Moral Implications of the Rise in the Incidence of Multiple-fetus Pregnancies and Multiple-child Births: Some Reservations About the Use of Fertilityenhancement and Pregnancy Reduction 131 Roger Β. Dworkin: Hard Cases for Autonomy, Respect, and Professionalism in Medical Genetics 153

Vili

Inhaltsverzeichnis

Jan C. Heller : Testing the Limits of Parental Choice: Using Genetic Applications to Produce Disabled Children 165 David Heyd: From Wrongful Life to Wrongful Identity. A (Controversial) Solution of a Hard Case 173 Jan C. Joerden: The Planned Transplant

181

Albrecht E. Sippel : The Medical Application of Human Embryonal Stem Cells

191

Veränderung genetischer Information - Changing Genetic Information Uoyd Cohen: Fixing the Race: Re-Engineering the Human Germline Thomas Crofts/Peter

201

Stanglow : Treatment of Disease or Genetic Enhancement?

219

Eike-Henner W. Kluge: Genetic Engineering: Some Ethical Considerations

249

Thomas Nenon/S. Edward Stevens , Jr.: Successful Enhancement: A Messy Case

273

Gregory Stock: Challenges of the Future Richard M. Zaner: The Brave New World of Genetics

287 297

Abhandlung Hans-Ulrich Hoche: Eine wollenslogische Weiterentwicklung des Universellen Präskriptivismus und die Begründung der Goldenen Regel 325

Rezension Erwin Bernat (Hrsg.), Die Reproduktionsmedizin am Prüfstand von Recht und Ethik (Marcus Düwell) 379 Erwin Bernat, Wolfgang Kröll (Hrsg.), Intensivmedizin als Herausforderung für Recht und Ethik (Frank Oehmichen) 382

Inhaltsverzeichnis

IX

Ralf Stoecker: Der Hirntod. Ein medizinethisches Problem und seine moralphilosophische Transformation (Dieter Schönecker) 385 Claudia Wiesemann, Die heimliche Krankheit. Eine Geschichte des Suchtbegriffs (Matthias Kaufmann) 388

Autoren- und Herausgeberverzeichnis / Contributors and Editors

391

Personenverzeichnis/Name Index

394

Sachverzeichnis /Subject Index

397

Hinweise für Autoren

401

Information for Authors

403

Schutz und Gewinnung genetischer Information Protecting and Obtaining Genetic Information

The Relaxin Opposition Revisited Roger Browns word I. Introduction The particular focus of this paper is the Relaxin Opposition1, the leading case at the European Patent Office on the patentability of inventions involving human genetic material. Without doubt, Relaxin is a "hard case", in the sense that it raises deeply contested issues at both bio-legal and bio-ethical levels. Without doubt, too, although Relaxin resolved those issues as between the parties to the particular dispute (and in relation to the particular claims made), the question of whether inventions of this kind should be treated as patentable - especially the question of whether human gene sequences or copies thereof (that is, genes isolated from the human body) should be patentable - remains a question that divides opinion around the world. My discussion of the Relaxin case is presented in four parts. First, I will simply outline the issues raised by Relaxin . Here, it is important to understand that the Opposition was argued (and duly rejected) within the legal framework established by the European Patent Convention (EPC), Article 53(a) of which provides for the exclusion of patents on grounds of (im)morality. Secondly, I will review the case in the light of the legal framework (particularly the morality exclusion provided for by Article 6) now laid down by the Directive on the Legal Protection of Biotechnological Inventions,2 a framework that does not replace but rather sits alongside the EPC. Thirdly, I will consider whether the opponents' dignity-based objections, in the Relaxin case, derive any support from, so to speak, the "new bioethics", this comprising the new EU Directive, the Council of Europe's Convention on Human Rights and Biomedicine3 (the so-called Bioethics Convention) and the UNESCO Declaration on the Human Genome and Human Rights,4 each of J 0JEP06/1995, 388; [1995] EPor541. 2 Directi ve 98/44/EC; OJL 213, 30. 7.98, p. 13. 3 Council of Europe , Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (DIR/JUR (96) 14) (Strasbourg: Directorate of Legal Affairs, November 1996). 4 This Declaration, adopted unanimously by the General Conference on November 11, 1997, is the result of more than four years work by UNESCO's International Bioethics Committee.

Roger Brownsword

which treats respect for human dignity as a cornerstone of bioethics and biolaw. Finally, I will present some brief remarks about the quest for rational law and the attempt to instate a defensible patent regime in Europe. Stated shortly, the gist of my discussion can be captured in the following points: (i) that, in principle (and, not least, for the sake of consistency in European patent law), the kind of objections presented by the opponents in the Relaxin case must also be arguable under the new Directive; (ii) that, on one reading, the Directive provides that, in cases such as Relaxin (where human tissue is donated to researchers), a pre-condition to patentability is that informed consent is given both to the taking and to the future commercial exploitation of inventive products arising from the research; (iii) that appeals to human dignity in the new bioethics might encourage a (misconceived) objection to the Relaxin patents along the lines that tissue donors act immorally in the sense that their participation in the research compromises their own dignity; (iv) that such an objection is out of place in a culture (of the kind now organised around the European Convention on Human Rights) that adopts a rights-led approach to the valuation of individual autonomy; and (v) that a rationally defensible patent regime will make the focus for moral exclusion from patentability the question of whether (dignity-supported) human rights are likely to be (or already have been) compromised by the applicant.

II. The Relaxin Opposition The Relaxin Opposition, where the patent at issue covered claims inter alia to "a DNA fragment encoding a polypeptide having human H2-relaxin activity" (Claim 3 of 21), arose under the European Patent Convention (EPC). According to the EPC, patentability is determined initially by Article 52(1), which provides: European patents shall be granted for any inventions which are susceptible of industrial application, which are new and which involve an inventive step.

However, the technical criteria in Article 52(1) must be read in conjunction with the exclusionary provisions of Article 53. First, Article 53(a) provides that patents shall not be granted for inventions the publication or exploitation of which would be contrary to 'ordre public' or morality, provided that the exploitation shall not be deemed to be so contrary merely because it is prohibited by law or regulation in some or all of the Contracting States.

Secondly, Article 53(b) provides that patents shall not be granted for plant or animal varieties or essentially biological processes for the production of plants and animals; this provision does not apply to micro-biological processes or the products thereof.

Both limbs of Article 53 have given rise to interpretive difficulties in the face of patent applications involving genetic engineering - notably, in the Onco-mouse 5

The Relaxin Opposition Revisited

5

application (which concerned a transgenic test animal for cancer research), and subsequently in the Plant Genetic Systems case6 (which concerned a genetically modified herbicide-resistant plant). However, with regard to patents on human gene sequences, Article 53(a) is the key exclusionary provision - and, in Relaxin , it was on the basis of this first limb of Article 53 that the opponents argued for revocation of the patent.7 The opponents' objections were articulated in three specific arguments: (1) that the "isolation of the DNA relaxin gene from tissue taken from a pregnant woman is immoral, in that it constitutes an offence against human dignity to make use of a particular female condition (pregnancy) for a technical process oriented towards profit"; (2) that patenting genes of this kind "amounts to a form of modern slavery since it involves the dismemberment of women and their piecemeal sale to commercial enterprises throughout the world" - thereby infringing "the human right to self-determination"; and (3) that the "patenting of human genes means that human life is being patented", which is "intrinsically immoral." The Opposition Division rejected all three arguments. Having conceded that the patenting of human DNA would be immoral "if it were true that the invention involved the patenting of human life, an abuse of pregnant women, a return to slavery and the piecemeal sale of women to industry", the Opposition Division rejected each of the specific objections. As to the first argument, the Opposition Division pointed out that those who had donated the tissue had done so consensually; and, moreover, there was no reason to doubt the morality of procedures of this kind (for many life-saving substances, such as blood-clotting factors, had been developed in this way). The second argument, it was said, betrayed a fundamental misunderstanding. A patent covering DNA encoding human H2-relaxin did not confer on the proprietor a right to any part of any particular human being. No woman was enslaved by the patent; the right to self-determination simply was not affected. As for the idea that the patent entailed the dismemberment and piecemeal sale of women, quite the contrary was the case - the whole point of the invention was to enable human H2-relaxin to be produced in a technical manner outside the human body. Finally, the Opposition Division dismissed the argument that patents on genes (even on the whole human genome) amounted to the patenting of human life. There is, the Opposition Division said, more to a human being than the sum of its genes. Furthermore, if the opponents had no objection to the patenting of human proteins, they could not consistently object to the patenting of human genes encoding such proteins. 5 OJ EPO 11 / 1989, 451 (first decision by examiners); OJ EPO 12/1990, 476 (Board of Appeal); OJ EPO 10 / 1992,590 (reconsidered decision by examiners). 6 Opposition Proceedings EP 0 242 236 B1 (Opposition Division); Τ 0356/93 (Board of Appeal). 7 Generally, see Deryck Beyleveld and Roger Brownsword, Mice, Morality, and Patents (London: Common Law Institute of Intellectual Property, 1993); and Sigrid Sterckx (ed), Biotechnology, Patents and Morality (Aldershot: Ashgate,1997).

Roger Brownsword

There are many points that could be taken up for further discussion from the Opposition Division's reasoning. However, for present purposes, two issues need to be flagged at this stage. First, the Opposition Division interpreted its exclusionary jurisdiction under Article 53(a) as coming into play only in the most exceptional of cases, essentially where the grant of a patent would be so abhorrent as to be inconceivable.8 Given this reading of the morality exclusion, the opponents faced the considerable hurdle of demonstrating that there was "an overwhelming consensus amongst the contracting states that the patenting of human genes is abhorrent and hence prohibited under Article 53(a)."9 Not surprisingly, they failed relative to this test. Secondly, the core of the opponents' case was that the grant of the patent was inconsistent with respect for human dignity. This claim, as we have seen, was elaborated in a number of more specific objections; and, whilst the Opposition Division addressed those specific objections, the more general objection invoking respect for human dignity was not squarely addressed. These features of the Relaxin reasoning invite two questions. One question is whether the opponents' arguments would fare any better if they were to be presented under the legal framework brought in by the new Directive on the Legal Protection of Biotechnological Inventions; and the other question is whether the objection based on human dignity would now be assisted by the instruments comprising the new bioethics. These are the questions to which we now turn.

I I I . Relaxin and the Directive on the Legal Protection of Biotechnological Inventions How would the arguments presented in Relaxin look if we were to review them through the lens of the recently agreed Directive on the Legal Protection of Biotechnological Inventions? We can start by looking at the general objection that the patent should be excluded on moral grounds and then we can consider the particular objection that the tissue donors (the pregnant women) were "used" - in the sense that they were treated in a way that failed to recognise their status as bearers of human rights, thus compromising their human dignity.

7. The general objection As is well-known, the patentability of human gene sequences was the most contested issue of principle during the ten-year debate that accompanied the passage 8 According to the EPO Guidelines, examiners should "consider whether it is probable that the public in general would regard the invention as so abhorrent that the grant of patent rights would be inconceivable" - and a letter bomb is given as an example of an invention that could not be patented without being universally condemned as outrageous. 9 See para. 6.4.3.

The Relaxin Opposition Revisited

7

of the Directive. Eventually, a compromise was struck and this is reflected in Articles 5 and 6 of the Directive, as well as in a number of key Recitals. Insofar as patents on human genes are opposed on the ground that the mere discovery of a gene fails the test of inventiveness, Article 5(1) thus concedes the point to the objectors: The human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene, cannot constitute patentable inventions.

On the other hand, the limits of this concession are signalled by Article 5(2), which states: An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element.

To this, Article 5(3) adds that it is a condition of patentability that the "industrial application of a sequence or a partial sequence of a gene [is] disclosed in the patent application." If we assume a distinction between unisolated human gene sequences (in a person's body) and isolated copies of human gene sequences (in a laboratory), the effect of these provisions is to treat the former as unpatentable (under Article 5(1)) and the latter as patentable provided that the copy is produced by means of a technical process (Article 5(2)) and provided that the industrial application of the sequence is disclosed (Article 5(3)). On the face of it, therefore, Article 5 would not exclude the patent granted to the claimants in Relaxin. However, the Directive, like the EPC, incorporates a morality exclusion. First, Article 6(1) of the Directive (in language that quite closely resembles that of Article 53(a) of the EPC) provides: Inventions shall be considered unpatentable where their commercial exploitation would be contrary to ordre public or morality; however, exploitation shall not be deemed to be so contrary merely because it is prohibited by law or regulation.

Secondly, Article 6(2) provides: On the basis of paragraph 1 [i.e. Article 6(1)], the following, in particular, shall be considered unpatentable: (a) processes for cloning human beings; (b) processes for modifying the germ line genetic identity of human beings; (c) uses of human embryos for industrial or commercial purposes; (d) processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes.

Article 6 builds on a number of Recitals. Most obviously, Article 6(1) draws on Recital 37 (in conjunction with Recital 39); 10 and Article 6(2) draws on Recital 38 2 Jahrbuch für Rechi und Kthik. Bd. 9 (2001)

Roger Brownsword

(in conjunction with Recitals 40, 41, 42, and 45). 11 However, other Recitals are clearly relevant to the interpretation of Article 6, particularly, we suggest, Recitals 16, 26, and 43. 12 The question to be considered is how the arguments raised by the opponents in the Relaxin Opposition would look in the light of Article 6 of the Directive. Would (and should) the opponents have any more success if their case had been argued under the Directive? As drafted, Article 6 combines a general test for exclusion on moral grounds (in Article 6(1)) with a number of specifically identified exclusions (in Article 6(2)). If a particular process or use is on the black-list in Article 6(2), the case for exclusion is fairly straightforward (although the application of Article 6(2)(d) would not be mechanical). However, if the particular case is not on the black-list, the argument for exclusion on moral grounds turns back to the general test in Article 6(1). Given that human gene sequences, or copies thereof, are not excluded by the express provisions of Article 6(2), an opposition of the kind advanced in Relaxin would need to find a footing in Article 6(1). It might be argued that, correctly interpreted, the Directive gives no such footing. First, it might be argued that, with regard to the particular question of the patentability of copies of human gene sequences, Article 5 settles the issue. However, why should we assume that Article 5 is to be read as taking priority over Article 6? Quite simply, it will be said, because the jurisprudence of European patent law, as developed under the EPC, operates with the canon of construction that exclusions from patentability are to be construed narrowly. 13 Secondly, even if it is conceded that Article 6 is relevant, nevertheless it cannot be read as excluding patents on copies of human gene sequences because neither Article 6(1) nor Article 6(2) makes explicit provision for such inventions to be excluded. Given that this question must have been uppermost in the minds of the drafters of the Directive, it would be a mistake to imply such an exclusion - if the drafters had had any moral reservations about the patentability of such matter, they surely would have so provided explicitly in Article 6. 10 The first part of Article 6( 1 ) copies in Recital 37. Recital 39 is drafted in obscure terms but, whatever else it might mean, it certainly signals that it is important to attend to moral considerations in the field of biotechnological inventions. 11 For the text of Recital 38, and discussion of its relationship to Article 6(2), see below at pp. 9 and 10. Recitals 40, 41,42, and 45 relate to each of the four specific exclusions listed in Article 6(2). 12 For discussion of Recitals 16 and 26, see below note 14 and pp. 11 and 12. Recital 43 rehearses the EU's commitment "to respect fundamental rights, as guaranteed by the European Convention for the Protection of Human Rights and Fundamental Freedoms.. .and as they result from the constitutional traditions common to the Member States, as general principles of Community law." w See e.g., the Plant Genetic Systems case (ΊΓ356/93) [1995] EPOR 357, at 367: "[T]he exceptions to patentability have been narrowly construed, in particular in respect of plant and animal varieties.. ..In the Board's view, this approach applies equally in respect of the provisions of Article 53(a) EPC."

The Relaxin Opposition Revisited

9

Thirdly, it might be argued that in the Recitals - particularly in those Recitals that bear most directly on the point - there is simply no support for the view that copies of human gene sequences should be treated as excluded on moral grounds. For example, Recital 38, which relates very closely to Article 6(2), provides as follows: Whereas the operative part of this Directive should also include an illustrative list of inventions excluded from patentability so as to provide national courts and patent offices with a general guide to interpreting the reference to ordre public and morality; whereas this list obviously cannot presume to be exhaustive; whereas processes, the uses of which offend against human dignity, such as processes to produce chimeras from germ cells or totipotent cells of humans and animals, are obviously also excluded from patentability.

Granted, Recital 38 indicates that the list in Article 6(2) is not exhaustive. Even so, an exclusion for copies of human gene sequences could not be read into Article 6(2) without wholly eradicating the saving for such material so carefully crafted in Articles 5(2) and 5(3); added to which, when Recital 38 itself offers further examples of processes to be excluded as offending against human dignity, the example given is that of chimeras rather than human gene sequences.14 Against this reading of the Directive, opponents of patents on copies of human gene sequences might marshall a number of responses. First, it might be argued that the EPC jurisprudence favouring a narrow construction of exclusions simply begs the question. After all, it is in the nature of moral reason that it sets overriding standards for patentability, the logic of which is that moral exclusions must be taken seriously. Accordingly, we should not think of a patent regime as an instrument for granting patents (subject to grudgingly accepted moral constraints); rather, we should think of patentability as an exercise involving both technical and moral judgments, with no presumption in favour of a grant simply because the technical criteria are satisfied. Secondly, the argument that the drafters of the Directive would have expressly provided for the exclusion of copies of human gene sequences had they so intended is a respectable one but hardly conclusive. As Lon Fuller highlighted in his classic article on the hypothetical case of the Speluncean Explorers, we should not read too much into a failure to make express legislative provision. 15 Moreover, in the context of Article 6, a failure to make express provision in Article 6(2) proves nothing about whether a particular kind of objection is arguable under the general test of Article 6(1). 14

Similarly, Recital 16 is inconclusive as to the question whether copies of human gene sequences might be argued to be unpatentable on moral grounds. Although the Recital opens by saying that "patent law must be applied so as to respect the fundamental principles safeguarding the dignity and integrity of the person", from which it follows that human gene sequences are not to be patented, it ends by reciting that such principles are "in line with the criteria of patentability proper to patent law, whereby a mere discovery cannot be patented." »5 Lon L Fuller, "The Case of the Speluncean Explorers" (1948-49) 62 Harvard Law Review 616. 2'

IO

Roger Brownsword

Thirdly, Recital 43 rehearses the commitment of the EU to respect for the rights protected under the European Convention on Human Rights. It follows that, if the objection to the patenting of human genes is either that human rights under the ECHR are violated, or that human rights logically extended from the ECHR are violated, 16 then the point must be arguable under Article 6(1). In principle, these arguments and counter-arguments might lead to one of three interpretations of the Directive as follows: (i) patents on copies of human gene sequences are never open to challenge on moral grounds; (ii) patents on copies of human gene sequences are open to challenge on moral grounds on a case-by-case basis; or (iii) patents on copies of human gene sequences are always excluded on moral grounds. The first of these interpretations is unconvincing because it treats Article 5 as settling not only the technical conditions for the patentability of copies of human gene sequences but also the moral questions addressed by Article 6. The third interpretation, deriving no assistance from Article 6(2), is equally unconvincing. The second interpretation not only looks plausible within the terms of the Directive, it fits better with the jurisprudence associated with the European Patent Convention. Assuming that the Directive allows for such a challenge under Article 6, the way would then be cleared for a dignity-based opposition of the kind advanced in the Relaxin case. Whether or not such a challenge would, or should, succeed is another matter. It is eminently arguable that respect for human dignity is one of the cornerstone principles of the Directive (this can be derived from Recital 38 in conjunction with the first three examples given in Article 6(2) as well as from Recital 16 and the provisions of Recital 43, integrating the Directive with the fundamental rights guaranteed by the European Convention on Human Rights). However, the concept of human dignity is open to many competing interpretations, 17 and we must reserve judgment on this point until the next part of the paper.

2. The objection that the tissue donors were "used" One way of developing the objection to the patent in the Relaxin case would be to focus upon the processes under which the tissue was taken by the researchers. Were the tissue donors "used"? Were their rights taken seriously and properly respected, or were they simply "instrumentalised"? Whilst it is arguable that Article 16 Cf. Deryck Beyleveld, "Legal Theory and Dialectically Contingent Justifications for the Principle of Generic Consistency" (1996) 9 Ratio Juris 15. 17 See Deryck Beyleveld and Roger Brownsword "Human Dignity, Human Rights, and Human Genetics" (1998) 61 Modern Law Review 661, esp. at 674-676; and "Patenting Human Genes: Legality, Morality, and Human Rights" in J. W. Harris (ed.), Property Problems - From Genes to Pension Funds (London: Kluwer Law International, 1997) 9, esp. at 19-22. And cf. Alain Pottage , "The Inscription of Life in Law: Genes, Patents, and Bio-politics" (1998) 61 Modern Law Review 740.

The Relaxin Opposition Revisited

11

6(1) is drafted in a way that restricts objections based on anything other than the morality of the future commercial exploitation of the invention, I will assume that it permits a broader range of objections, including objections looking back at the research and development of the invention. 18 On this assumption, Recital 26 of the Directive seems to be a highly relevant provision in relation to objections of this kind. Recital 26, which appears at the end of a cluster of Recitals dealing with the matters provided for in Article 5, states: Whereas if an invention is based on biological material of human origin or if it uses such material, where a patent application is filed, the person from whose body the material is taken must have had an opportunity of expressing free and informed consent thereto, in accordance with national law.

On the face of it, this not only underlines the European view that insists upon there being informed consent as a pre-condition to the taking of human material (at least from the living), it also links directly to Article 6(1), inviting opposition to patents where informed consent requirements have not been properly satisfied. 19 Yet, would this combination of provisions have assisted the opponents in the Relaxin case where the Opposition Division accepted that "the women who donated the tissue consented to do so within the framework of necessary gynaecological operations"? 20 This, after all, seems a long way removed from the notorious John Moore case in California. 21 The most robust interpretation of Recital 26 would have it that free and informed consent must be given not only to the taking of the tissue but also to the use of the tissue in research work that might lead to an application for a patent. In other words, the donor's consent must reach right through to the possibility of patenting (and, by implication, to subsequent patent-protected commercial exploitation). It is not clear whether the consent of the donor women in Relaxin would have satisfied such a stringent requirement. If not, on this interpretation of Recital 26 and Article 6(1), the patent should be excluded as immoral. Against this, however, the drafting of Recital 26 gives some encouragement to a range of weaker interpretations (interpretations that make allowance for the inconvenience (or impossibility) of obtaining informed consent). '8 For discussion, see Deryck Beyleveld , Roger Brownsword, and Margaret Llewelyn, "The Morality Clauses of the Directive on the Legal Protection of Biotechnological Inventions: Conflict, Compromise, and the Patent Community" (forthcoming). 19 See, too, Article 22 of the Council of Europe Convention on Human Rights and Biomedicine and the UNESCO Universal Declaration on the Human Genome and Human Rights. 2 Para. 6.3.1. 2i Moore ν Regents of the University of California (1990) 793 P2d 479. For discussion and critique, see, e.g., James Boyle, Shamans, Software, and Spleens (Cambridge, Mass.: Harvard University Press, 1996) esp. at pp. 21-24 and 99-107; and Deryck Beyleveld and Roger Brownsword, note 22 below.

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Insofar as such weaker interpretations simply allow for some kind of surrogate test (best interests or substituted judgment or the like) where a person is not able to give free and informed consent, there is no great problem. The critical question is how we read the requirement where persons are able to give free and informed consent. Prima facie, the purpose of the closing clause of Recital 26, which speaks of informed consent "in accordance with national law", is to make the requirement contingent in some sense upon the position taken by national legal systems. If this simply signals scope for some national variation in relation to the particular procedures used for obtaining consent, then there is again no real problem. However, if national law is allowed to set the standard for, and scope of, free and informed consent then the robust view is seriously undermined. For, this would mean that a challenge under Article 6(1) would be limited to ensuring that patent holders respect the consent requirements written into their own national legal regimes. On this view, provided that the donors in Relaxin were treated in accordance with national consent requirements, they could not be said to have been used - their (posited national) rights would have been respected. Moreover, even if a local regime set high standards for informed consent, it remains moot whether the required consent contemplated by Recital 26 runs beyond the taking of the tissue to the taking out of a patent (or the attempt to develop the material for the purpose of producing a patentable invention). In treatment settings, the very idea of free and informed consent is, of course, deeply problematic. 22 However, Recital 26 and Article 6(1) add to the complexity of consent by leaving two key issues unclear: first, how far (if at all) researchers must comply with consent requirements that are independent of national requirements; and, secondly, whether donors must have notice of, and give consent to, possible patent applications at some future time.

22 Generally, see P. Schuck, "Rethinking Informed Consent" (1994) 103 Yale Law Journal 899. Specifically, in relation to the taking of human material, the Nuffield Council on Bioethics . in its Report, Human Tissue: Ethical and Legal Issues (London, 1995), draws a distinction between treatment and non-treatment situations. The Council has a different recommendation when the material is removed for the purpose of treatment - in which case, specific consent to particular uses is not required - from when the material is removed for purposes other than treatment - in which case, specific consent is required. This should be contrasted with the position taken by the Health Council of the Netherlands , in Proper Use of Human Tissue (Publication No 1994/01E) (The Hague, 1994), which requires specific consent in both cases. However, though we agree with the Health Council of the Netherlands, we should note that Article 22 of the Convention on Human Rights and Biomedicine states merely that the taking of human tissue must be subject to the "appropriate consents being given," leaving judgment about this to national discretion. See further, Deryck Beyleveld and Roger Brownsword, "Articles 21 and 22 of the Convention on Human Rights and Biomedicine: Property and Consent, Commerce and Dignity" in Peter Kemp (ed) Research Projects on Basic Ethical Principles in Bioethics and Biolaw (Copenhagen: Centre for Ethics and Law, 1998) 33.

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IV. Dignity-Based Opposition and the New Bioethics Since the Relaxin case was decided, and in addition to the new Directive, there have been two major new bioethics instruments, the Council of Europe's Convention on Human Rights and Biomedicine and the UNESCO Universal Declaration on the Human Genome and Human Rights. In the Preamble to the former, the signatories resolve "to take such measures as are necessary to safeguard human dignity and the fundamental rights and freedoms of the individual with regard to the application of biology and medicine"; and, similarly, in the Preamble to the latter an instrument peppered with references to human dignity and human rights - it is emphasised that research on the human genome "should fully respect human dignity, freedom and human rights". Strikingly, in both instruments, modern bioethics is being developed, not merely around respect for human rights, but around the centrality of respect for human dignity. Does this add force to the opponents' dignity-based opposition in the Relaxin case, or are appeals to human dignity merely rhetorical flourishes that are, as John Harris would have it, "comprehensively vague"? 23 In both legal instruments and philosophical discussion, human dignity appears in a variety of guises. Sometimes, as in the so-called International Bill of Rights (comprising the Universal Declaration on Human Rights and its accompanying Covenants, ICESCR and ICCPR) human dignity is equated with human beings having value or worth which grounds their having rights - here, the equal and inalienable rights of human beings are said to "derive from the inherent dignity of the human person". 24 The logic of this view is that any violation of human rights implicitly violates human dignity. In some cases, though, respect for human dignity is specifically associated with particular human rights (for example, rights concerning the basic conditions for working people and for those who have been deprived of their liberty). In the new bioethics, however, we glimpse two critical ideas: first, the idea that the key to the protection of embryonic and potential human life might be human dignity rather than human rights; and, secondly, the idea (signalled most clearly by the prohibition on commercialisation of the human body) that dignity might be compromised by our own (self-regarding) actions as much as by the unwilled interferences of others. Now, insofar as we treat the new bioethics as evolving from the ruling autonomy-centred scheme seminally devel-

23 John Harris , Clones, Genes, and Immortality (Oxford: Oxford University Press, 1998) ρ 31. For another sceptical view (human dignity as a "conversation stopper"), see Dieter Birnbacher, "Do Modern Reproductive Technologies Violate Human Dignity?" in Elisabeth Hildt and Dietmar Mieth (eds), In Vitro Fertilisation in the 1990s (Aldershot: Ashgate, 1998) 325. 24 Cf. the Preamble to the African Charter on Human and Peoples' Rights, 1981, where fundamental human rights are said to "stem from the attributes of human beings"; and, similarly, the Preamble to the American Convention on Human Rights, 1969, which states that "the essential rights of man.. .are based upon attributes of the human personality".

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oped by Beauchamp and Childress - and it is instructive, indeed, to compare the standard test cases presented by Beauchamp and Childress with the "hard cases" presented in this collection of essays26 - then the bearing of these two ideas in relation to that scheme needs to be observed very carefully. The first idea, that respect for human dignity is the key to protection of the human embryo, supplements the ruling scheme by protecting early human life at a stage when the capacities to which autonomy is generally thought to relate are not yet developed. This, however, is not without implications for the centrality of autonomy; it is not as though dignity simply kicks in to protect life where autonomy runs out. Rather, if embryonic and fetal life is protected under the cover of respect for human dignity (in its new extended sense), the autonomous choices of researchers (for example, to create, test, manipulate, and store embryos) and of women (to terminate pregnancies) can no longer be regarded as acting on life forms that have no protected moral status. Quite how far we judge that autonomy is limited depends, of course, on how we interpret the new conception of human dignity together with its protective effects. Ultimately, the bounds of legal permissibility may not alter very much (because we are deep into the politics of compromise in these areas) but the emergence of human dignity in this way might at least be significant in that it changes the terms of debate 2 7 The second idea, that certain uses of our own bodies involve compromising our own dignity, limits autonomy even more directly. The way in which human dignity, in this sense, has the potential to constrain autonomy is strikingly illustrated by the famous Conseil d'Etat ruling that dwarf-throwing ("lancer de nain") was incompatible with "ordre public", 28 because the dwarfs (one of whom was challenging the police bans) compromised human dignity by allowing themselves to be used as mere things. 29 Similarly, in the context of commerce in one's own body parts, the 25

Tom L. Beauchamp and James F. Childress . Principles of Biomedical Ethics, 4 t h ed (Oxford: Oxford University Press, 1994). An interesting example of the attempt to articulate a new bioethics in Europe is represented by Peter Kemp's project on "Basic Ethical Principles in Bioethics and Biolaw", see Ethical, Legal and Social Aspects of the Life Sciences and Technologies Programmes of the Fourth Framework Programme: Catalogue of Contracts (European Commission. 1998) pp. 30-32. According to the terms of this project, the principle of autonomy is not to be "left aside", but further principles are needed "to express the foundation or the rationality of respect and responsibility towards human beings" (p. 31). The three key additional principles are said to be "dignity, integrity and vulnerability" (ibid). 26 Beauchamp and Childress present ten test cases in an Appendix to their book (note 25 above), at pp. 509-526. These cases concern such matters as confidentiality and information giving/withholding, organ donation, cessation of treatment (including pvs cases), dealing with the mentally incompetent, and surrogacy. Ethical puzzles associated with developments in modern genetics, ranging from pre-implantation diagnosis to various cloning scenarios (as strongly represented in the present collection), have yet to enter the lists. 27 In the context of debates about abortion and euthanasia, cf. Ronald Dworkin, Life's Dominion (London: Harper Collins, 1993). 2 « Conseil d'Etat (October 27, 1995) req. nos. 136-727 (Commune de Morsang-sur-Orge) and 143-578 (Ville d'Aix-en-Provence).

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Warnock Committee noted that some opposition to surrogacy was based on the ground that "it is inconsistent with human dignity that a woman should use her uterus for financial profit and treat it as an incubator for someone else's child" 3 0 ; and, extending this logic, the prevailing view seems to be that respect for one's own dignity militates against gene-selling and financial gain from commerce in body parts. 31 To return to the opposition in the Relaxin case, the opponents might be encouraged by the new bioethics to argue that, even if the pregnant women freely donated their tissue, even if they freely consented to the use of their tissue for research and, indeed, even if they were perfectly aware that patent applications and commercial exploitation by the patent proprietors might follow, these considerations would be irrelevant because the donation and use of human tissue violates human dignity the donors, in other words, compromised their own dignity. What would we make of such an argument? At one level, we might find the argument, on the Relaxin facts, wholly unconvincing. Assuming that the tissue was donated, rather than sold, the women could not be said to be "putting a price" on their bodies.32 Moreover, to argue that human dignity is violated whenever any human material is freely donated in medical settings implies that the collection of, say, blood or organs is immoral. Of course, some might be perfectly happy to accept such implications; but such radical and restrictive consequences are hardly compatible with the broad consensus on which the new bioethics purports to build. At another, more fundamental, level, we might resist such an argument on the ground that it makes a philosophical error by presenting a tension between human

29 See Marie-Christine Roualt's note on the two decisions, Les Petites Affiches (January 24, 1996: No. 11) 30, at 32; and, Bernard Edelman , "La Dignité de la Personne Humaine, un Concept Nouveau", Recueil Dalloz 1997,23e Cahier, Chronique, 185, 187-188. 30 Report of the Committee of Inquiry into Human Fertilisation and Embryology (Lond HMSO, 1984), para 8.10. 3' See Article 4 of the Universal Declaration on the Human Genome and Human Rights ; and Article 21 of the Convention on Human Rights and Biomedicine . 32 In The Metaphysics of Morals (translated and edited by Mary Gregor) (Cambridge: Cambridge University Press, 1996) (first published 1797) at p. 209, Immanuel Kant famously wrote about human dignity in the following way: "Every human being has a legitimate claim to respect from his fellow human beings and is in turn bound to respect every other. Humanity itself is a dignity; for a human being cannot be used merely as a means by any human being ... but must always be used at the same time as an end. It is just in this that his dignity (personality) consists, by which he raises himself above all other beings in the world that are not human beings and yet can be used, and so over all things. But just as he cannot give himself away for any price (this would conflict with his duty of self-esteem), so neither can he act contrary to the equally necessary self-esteem of others, as human beings, that is, he is under obligation to acknowledge, in a practical way, the dignity of humanity in every other human being. Hence there rests on him a duty regarding the respect that must be shown to every other human being."

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dignity and autonomy. If we stick with the idea that human dignity is the basis on which human rights are held/ 3 then the limits of our autonomy are set by the rights of others (and, correlatively, our duties to others) not by duties to ourselves (not to compromise our own dignity). Once we debate this issue at this level, we must address the different ways in which respect for dignity is incorporated in rights-led, as opposed to duty-based, moral theories. Although this is not a discussion into which I can enter here, it seems to me to be fairly clear that the prevailing culture of human rights in Europe is rights-led and that the logic of a rights-led moral theory is that autonomy is grounded in human dignity, not limited by it. 3 4 If the drift of these remarks is correct, we would have to say that, although the new bioethics might prompt a fresh line of dignity-based challenge in the Relaxin case, such an opposition would not be well-founded. Rather than arguing that the donor women might have compromised their own dignity, we should continue to question whether their autonomy was respected - whether, in other words, their consent was free and fully informed.

V. Relaxin and Rational Law How can we best gather up the strands of this discussion? One way of collecting together our critical thoughts about the law, as I have suggested elsewhere, is that we should test out particular phenomena (particular doctrines or decisions) for their rationality. 35 What, though, does a commitment to rationality signify? According to Robert Nozick, "[to] term something rational is to make an evaluation : its reasons are good ones (of a certain sort), and it meets the standards (of a certain sort) that it should meet." 36 When we evaluate the law for its rationality, it seems to me that three desiderata are material, these representing the standards that we judge that the law should meet and the reasons that we count as good ones. First, to be rational, the law should be free from doctrinal contradiction; secondly, it should be effective in guiding action, and in achieving its intended purposes; and, thirdly, it should be legitimate (its reasons, in other words, should be good ones). 33 For a good example of this approach, see Alan Gewirth, Human Rights (Chicago: University of Chicago Press, 1982) 29. Similarly, in The Community of Rights (Chicago: University of Chicago Press, 1996) at p. 66, Gewirth emphasises that the attribution of worth to agents "encompasses not only their purposiveness as such but also the abilities of reason and will that enter into their agency." He goes on to say: "Human dignity consists in having and at least potentially using these abilities, and human rights are derived from human dignity thus conceived" ibid. 34 For full discussion of this point, see Deryck Beyleveld and Roger Brownsword, "Human Dignity, Human Rights, and Human Genetics" (1998) 61 Modern Law Review 661. 35 See e.g., John N. Adams and Roger Brownsword, Key Issues in Contract (London: Butterworths, 1995) passim. 36 Robert Nozick , The Nature of Rationality (Princeton: Princeton University Press, 1993) p. 98.

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We can call these desiderata, respectively, the requirements of formal, instrumental, and substantive rationality. Relative to such criteria, does the Relaxin decision and, on a broader front, the European legal framework concerning the patentability of human genes, pass muster? First, do the overlapping regimes of patent law in Europe (the EPC and the Directive) meet the criterion of formal rationality? 37 As we have seen, these regimes are not identical. However, no one could accuse the drafters of the Directive of taking lightly the need for compatability with the EPC. Indeed, much of the difficulty for the drafters was that they were caught between the anti-patenting alliance at the European Parliament and their own self-imposed imperative that the Directive should square with the EPC and the decisions made at the EPO (including the Relaxin decision). Certainly, unless the Directive was thought to have instated a more demanding informed consent requirement than that applied under the EPC, we would expect the Relaxin opposition to fail under the Directive - and to do so for very much the same reasons that the Opposition Division gave in declining to revoke the patent. Secondly, by taking a liberal line on patentability, the Relaxin decision steers clear of a common complaint concerning instrumental rationality. Ulrich Schatz has expressed this line of thinking very clearly: [T]he consequence of exclusions of patentability does not mean that the excluded subjectmatter - e.g. transgenic plants, animals, drugs derived from human genes - would not be invented, would not be made, would not be on the market, would not be used.. ..But it will not have been invented by European enterprises.. ..It will be imported from America, Japan, Korea, everywhere you can think of, because you will have admitted it to the market. So, if you are concerned with patenting these things on moral grounds, you cannot avoid to first prohibit the making and sale of whatever you want to exclude.. ..As long as you have not done this, it is absolutely pointless to speak about patenting. The only point in that is that others will make these things, not European industry.38

Thus, it is argued that the moral high ground has a price. To exclude from patentability in Europe inventive work on the human genome simply moves that kind of business elsewhere. Moreover, unless Europe also extends its exclusion to a prohibition on commercial exploitation, the products of such invention will find their way back into the European marketplace. However, since Relaxin takes no such 3? There is, in fact, a further angle to this dimension of rationality. As Recitals 12 and 36 of the Directive note, the EC has signed the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), Article 27(2) of which states that it is permissible for patent regimes to have exclusions that are necessary for the protection of "public order or morality", this being said to include the protection of "human, animal or plant life" or the avoidance of "serious prejudice to the environment". From a TRIPS perspective, therefore, Article 6 of the Directive and Article 53(a) of the EPC are permissible; and, insofar as these moral exclusions copy in the elements of the provision in TRIPs, there is no problem about consistency. 3« Ulrich Schatz, "Patents and Morality" in Sigrid Sterckx (ed), Biotechnology, Patents and Morality (note 7 above) 159, at 170.

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exclusionary stance, it escapes such doubts about its practical instrumental rationality. On the other hand, we might accuse Relaxin of being instrumentally irrational in a rather different sense. As is well-known, from the early 1990s, when the US National Institutes of Health (together with Dr. Craig Venter) filed patent applications for sequences of DNA taken from brain cells, 39 the patenting of human gene sequences has developed rapidly to the point where it was estimated that, by the mid-1990s, over one thousand such patents (worldwide) had been granted. 40 Against this background, Relaxin seems unexceptional. However, the willingness of Patent Offices to file patents of this kind might be argued to be doubly damaging (instrumentally irrational). At one level, such a policy undermines the co-operative scientific spirit in which the Human Genome Project began. True, it was not the Patent Offices that took the first step to change the terms on which this international research collaboration was conducted; but, arguably, their readiness to grant patents arising from inventive work on the human genome inhibits informal scientific co-operation in both the short and the longer term. At another level, the granting of patents on copies of human gene sequences might be criticised as inhibiting scientific work by others on the patented part of the genome. If these claims are correct, Relaxin rewards some inventive work on the human genome but at the price of retarding and restricting other initiatives. Finally, and most controversially, there are questions about the moral rationality of the European patent regimes and their concomitant decisions. Would we now judge that the Relaxin case arrived at a morally defensible decision? The new bioethics, as we have seen, purports to reinforce the opponents' reliance on the importance of respect for human dignity. However, whether we place the new bioethics in the established culture of human rights in Europe, or in a less culturally-contingent rights-led moral theory, 41 it is hard to see how it advances the opponents' cause. What matters most is whether the rights of donors are respected; and, if there have been significant changes since the Relaxin Opposition fell for decision, it is perhaps that the Directive gives some assistance to those who wish w See Gerald Dworkin , "Ethics of Human Genome Analysis. Intellectual Property and Ownership of Data" in Hille Haker, Richard Hearn, and Klaus Steigleder (eds.) Ethics of Human Genome Analysis (Tübingen: Attempto Verlag Tübingen, 1993) 175, at 176- 177. ™ See 5. M. Thomas , A. R. W. Davies, N. J. Birtwisde, S. M. Crowther, and J. F. Burke , "Ownership of the Human Genome" 380 Nature (4 April, 1996) 387. In a survey recently carried out for The Guardian newspaper, Genewatch UK found a huge increase in the number of such patents applied for and granted since the mid-1990s; in fact, they found that more than 500.000 patents had been applied for worldwide on genes or gene sequences in living organisms (including humans). Moreover, the liberal approach at the EPO looks set to continue for the time being. See James Meek, "Envoys avoid gene patent issue", The Guardian, Nov. 30, 2000, p. 2. 41 For this kind of approach, applied to debates about the concept of law, see Deryck Beyleveld and Roger Brownsword, "Law as a Moral Judgment" (London: Sweet and Maxwell, 1986; reprinted Sheffield: Sheffield Academic Press, 1994).

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to take a harder look at the processes by which human tissue is gathered - at any rate, when there is a possibility that the tissue might be used with a view to developing a patent-protected product. One final caution is in order: insofar as these reflections imply that regulation of (and opposition to) the patenting of products and processes associated with research on the human genome might be better organised around a precise informed consent requirement rather than an imprecise concept of human dignity, nevertheless it would be premature to assume that informed consent is the complete answer and human dignity (beyond its role in directly underpinning human rights) no part of the solution. Paper regimes of informed consent, as we have said, do not always translate so well into practice. 42 And, while the concept of human dignity must not be let loose so that the majority are licensed to dictate the terms on which the minority lead their lives, there remains the sense that dignity is at least a practical virtue having a direct bearing on how humans should relate to a greater understanding of their own genome. Our difficulty - a difficulty shared perhaps by the opponents in the Relaxin case - is finding the right articulation of such a virtue.

Zusammenfassung Die möglicherweise kontroverseste Frage im Bereich des Biorechts ist die Frage danach, ob die Erforschung des menschlichen Genoms, insbesondere die Isolierung menschlicher Gene und die Identifizierung ihrer Funktionen, patentierbar sein sollte. Nach Jahren einer diesbezüglichen Debatte unterstützt die EU-Direktive zum rechtlichen Schutz von biotechnischen Entwicklungen nun die Pro-Patentierbarkeit-Lobby. Gleichzeitig wurde jedoch eine neue Konzeption der Bioethik in Europa formuliert, in der das Prinzip der Achtung der Menschenwürde eine zentrale Rolle spielt und aus deren Perspektive Patente auf menschliche Gene als unmoralisch ausgeschlossen sein sollten. Im Lichte dieser Entwicklungen untersucht dieser Beitrag den „ Relaxin-Einspruch", bei dem das Europäische Patentamt mit Argumenten konfrontiert wurde (und diese zurückwies), die den Gedanken der Menschenwürde gegen die Patentierbarkeit menschlicher Gene ins Feld führten. Die im vorliegenden Beitrag vertretene Auffassung geht dahin, daß, obwohl die Achtung der Menschenwürde ein wichtiges Kriterium für ein rational konzipiertes Patentrecht darstellt, es doch nicht ein völlig überzeugendes Argument gegen die Patentierbarkeit menschlicher Gene ist. Vielmehr ist die zentrale Frage die, ob die Patentierung menschlicher Gene generell und im Einzelfall mit der Achtung der Menschenrechte vereinbar ist (die ihrerseits in der Achtung der Menschenwürde begründet ist).

42 See, e.g., P. Schuck (note 22 above).

Using Newborn Blood Samples for Genetics Research: Thinking About the Context Ellen Wright Clayton The state of New York currently uses leftover newborn screening blood samples (blood spots) to assess allele frequencies of the gene associated with hereditary hemochromatosis (HH), a disease of iron overload.1 The parents of these infants are not told about and not asked whether they give their permission for using their children's samples in this project. All identifying information is removed from the residual spots before testing is done, thereby effectively eliminating the chance that any child or family will be harmed or helped by disclosure of research results. The question this paper will address is whether studies using blood spots present any reason for concern. At one level, newborn blood spots seem to be an ideal source of DNA for this project. They are the only easily accessible, already existing, population based source of DNA. Allele frequency is at least part of the information needed to understand diseases with genetic contributions. Given that the research results would have some utility, some ask why anyone might care whether these spots are used. After all, the blood has already been collected, albeit for a different purpose, so the babies are not going to get stuck again. Simply assessing allele frequency among newborns does little to answer most of the questions about HH that are actually clinically relevant. These include defining what proportion of those who have disease-causing alleles will actually develop disease (the so-called penetrance of the mutant alleles) and whether other genes or environmental factors alter the appearance of clinical disease. Hemochromatosis, like many other diseases, is protean in its manifestations. 2 Iron overload causes common disorders such as diabetes mellitus, cirrhosis, and heart failure, which themselves have numerous etiologies. Clinicians so frequently fail to recognize the role that iron overload plays in their patients' symptoms that the actual prevalence of hemochromatosis (the percentage of people in the population who are made ill by this disease) is unknown. Given the difficulties of doing clinical epidemiologic 1

Wads wort h Center, New York State Department of Health, The genetic dilemma, Biofocus, http://www.wadsworth.org/publish/biofocus/may98/genetic.htm, (May 1998). 2 Burke W, Thomson E„ Khoury M. 7., et ai, "Hereditary hemochromatosis: gene discovery and its implications for population-based screening", 280 JAMA 172-8 (1998).

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research, ascertaining the prevalence of symptoms caused by HH is far more difficult than measuring allele frequency. Newborn blood spots are a particularly unhelpful source of DNA if one needs to determine both the prevalence of disease and allele frequency for an adult-onset disease such as hemochromatosis. Assaying prevalence requires access to individuals' medical history. It is impossible to use DNA from and information about newborns to provide all the information needed to answer the critical questions about hemochromatosis because neonates are almost never affected. The same issues apply for most other adult onset diseases. That so little of the necessary information can be gleaned from research using newborn blood spots is one reason for thinking twice about using these samples for any purpose other than those for which they were originally collected. Even stronger reasons for caution in using residual newborn blood spots for research become clearer when one considers the way in which newborn blood spots are collected and the ongoing debates about how best to incorporate genetic testing into clinical care and to use human biological materials for research.

The unique nature of newborn screening programs. The states, through laws and regulations, direct that hospitals and clinicians obtain blood samples from virtually every child born in their state.3 These samples are sent to a state-run or authorized laboratory where they are tested for a variety of disorders, which can be effectively treated if therapy is begun in the newborn period prior to the onset of symptoms. Finding children affected with these diseases is the reason these programs were put into place. The blood spots, however, are rarely used up in the course of testing, and the residual samples are retained by the states for varying periods of time, ranging from a few months to perpetuity.4 The reasons given for retaining samples include use for quality assurance, follow up of affected children who were missed on screening, diagnostic testing for children who die unexpectedly, and in a few states, explicitly to identify missing children. 5 Only two states require that parental permission be sought for newborn screening.6 None require that parents be asked * Clayton E. W., "Screening and Treatment of Newborns", 29 Hous. L. Rev. 85-148 (1992). 4 Newborn Screening Task Force, "A Blueprint for the future: Recommendations from the Newborn Screening Task Force", draft 10/4/99. 5 Michigan Commission on Genetic Privacy and Progress, Final Report and Recommendations, http://www.mdmh.state.mi.us/mcgpp/final/, (February, 1999). 6 North Carolina and South Dakota. D. Wertz, "Newborn Screening: State Policies on Testing, Informed Consent, and Public Input, GeneLetter", http://www.geneletter.org/0398/ newborn.htm (March 1998). Massachusetts requires informed consent only for a pilot project screening for cystic fibrosis and a number of rare metabolic disorders. 105 CMR

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or even told about retaining these samples or about using them for research or for any other purpose. The origin of these collections and the fact that they were gathered without the knowledge or permission of the parents is all the more remarkable when one realizes that these are the only truly population-based DNA collections in existence. The question of how to respond to proposals to expand the number of disorders screened and to do research with these samples needs to weighed in light of the circumstances that led to the creation of these collections.

The time is not ripe for DNA report cards or even for broadly expanded state newborn screening programs· During the early 1990's, every talk about the ethical, legal, and social implications of the Human Genome Project and human genetics seemed to include a cartoon of a physician holding a newborn in one hand and a floppy disc with the baby's DNA sequence in the other. The progress that has been made in the last decade toward making that cartoon a reality, with the development of technologies such as Affymetrix's "gene chip" and the completion of a rough draft of the sequence, is breathtaking to even the most optimistic. At a recent conference entitled "Respecting Genetic Privacy," 7 participants spoke with great certainty about the imminent incorporation of the DNA profile into the medical record. At that meeting, Philip Reilly, whose previous works include an article entitled, "Stored Guthrie Cards as DNA Banks,"8 urged that that day will come even sooner than we know because it will be possible to create these profiles by using newborn blood spots that are still available for millions of Americans, particularly in states such as Massachusetts that have been saving their samples since the inception of their program thirty years ago. It is precisely this vision that demonstrates the need for caution for using blood spots for purposes other than those for which they were originally collected. This concern is not based on a nihilistic view that genetics is bad. Understanding aspects of an individual's genetic makeup can promote his or her health. To give just a few examples of ways in which this knowledge has already improved medical care, diagnosing PKU before it becomes clinically apparent and instituting a low phenylalanine diet can avert profound mental retardation. Knowing that a person has a mutation in the APC gene can alert him or her to the need to undergo early, routine colonoscopy that can detect cancers before they metastasize widely, per-

§ 270.006(B)(1999); New England Newborn Screening Program , Optional Screening, http:// www.umassmed.edu/nbs/screenings/optional/. 7 "Respecting Genetic Privacy: The First Annual ASU-SB Conference on Law, Science, and Technology", March 12-13, 1999. 8 McEwen J. A.. Reilly P. R.. "Stored Guthrie cards as DNA 'banks'," 55 Am J. Hum Genet. 196-200(1994). 3 Jahrbuch fur Rechi und Hihik, Bd. 9 (2001)

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mitting curative surgery. Those who look forward to the era of "genetic medicine" fail to recognize that it arrived some time ago. At the same time, the primary reasons for testing in our current system of medical care are to diagnose the cause of already existing symptoms, to improve the ability to predict the course of illness, and where possible, to start interventions that can prevent or ameliorate disease. The examples cited in the preceding paragraph fit these criteria easily. By contrast, identifying mutations that predispose or will cause currently healthy individuals to develop disease sometime in the future, particularly where no effective preventive interventions exist to alter the risk, fits poorly in this paradigm. As a result, many commentators have advocated caution in introducing new genetic tests into medical practice, calling in essence for clearly defined test characteristics and preferably for demonstrably effective interventions.9 In other words, they argue that genetic tests should be used only when they fit the current guidelines for diagnostic testing. Examples that demonstrate the need to adhere to the current paradigm are legion. To pick one of the most frequently discussed, when the BRCAÌ gene was first described relying on DNA obtained from very high risk families, it appeared that women who have a mutation in this gene have about an 85% chance of developing breast cancer some time during their lifetime. 10 Later work demonstrated that Ashkenazi Jewish women who have the 185delAG mutation in BRCAÌ have a 60% lifetime risk of developing breast cancer, which is considerably lower. 11 The penetrance of mutations in these genes in women who have little or no family history of breast and ovarian cancer is still unknown. In addition, little is known about how best to avert breast and ovarian cancer in women who have these mutations.12 In light of this uncertainty regarding both predictiveness and intervention, almost everyone agrees that BRCAÌ mutation analysis is not appropriately a part of routine care. Consensus also exists that genetic tests, like those for BRCAl which are of uncertain predictive value and for which intervention is not well established, should be used, if at all, only with the full knowledge and consent of the person being tested.13

y Holtzman Ν. Α., Watson M. S., eds., Promoting Safe and Effective Genetic Testing in the United States: Final Report of the Task Force on Genetic Testing, (1998). · Ford D., Easton D. F.. Bishop D. Τ , Narod 5. A.r Goldgar D. E., "Risks of cancer in BRCAI-mutation carriers 44. Breast Cancer Linkage Consortium, 343 Lancet 692-5 (1994). 11 Streuwing, Hartge, Wacholder, et al. , "The Risk of Cancer Associated with Specific Mutations of BRCAl and BRCA2 among Ashkenazi Jews", 336 New Engl. J. Med. 1401 (1997). 12 Burke, Daly , Garber, et ai, "Recommendations for Follow-up Care of Individuals With an Inherited Predisposition to Cancer: BRCAl and BRCA2 277 JAMA 997 (1997); But cf., Hartmann, L C., Schaid D. J., Woods J. E., et ai, "Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer", 340 Ν Engl J Med 77-84 (1999) (study in women who were known to be high risk but not stratified by presence or absence of mutations).

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Another factor that warrants caution in adopting new diagnostic tests is that physicians typically say little or nothing about the risks and benefits of most tests that are currently part of medical practice. Among the factors contributing to the lack of conversation regarding tests is an unspoken assumption that the benefits of testing are well proven and that tests would be accepted by most people who seek medical care. As a result, little point is seen in talking about tests, particularly since talking costs money. Even though this state of affairs is subject to obvious challenge,14 the relative lack of discussion of testing in clinical practice is likely to continue. As a result, the fact that so many people decline predictive and predisposition genetic testing when they understand the consequences,15 which is clear evidence that the unspoken assumptions do not apply, is further reason to be careful about incorporating these tests into routine care. The history of newborn screening in many ways parallels that seen in medical care more broadly. Since the introduction of newborn screening for PKU, states have tended to add one or two new disorders to the screening panel at a time. Sometimes legislatures add new disorders in response to constituent advocacy, the original force behind the enactment of newborn screening statutes. More often, state health departments add new tests, sometimes after engaging in feasability and cost analyses and sometimes after less formal discussion. As a result, states generally screen only for a handful of disorders. All of a sudden, the tempo has changed. Pressure to expand dramatically the number of diseases screened for has come not from new developments in DNA diagnostics but from increased capacity for inexpensive tandem mass spectrometry (TMS) which can screen for hundreds of disorders of protein and fatty acid metabolism. 16 One feature of this technology is that it can detect many disorders that are not amenable to effective amelioration or treatment. This is a problem since it is widely acknowledged that population based newborn screening is appropriate 13 American Society for Clinical Oncology, "Genetic Testing for Cancer Susceptibility", 14 J. Clin. Oncol. 1730-6(1996). 14 This is not necessarily to condone limited discussion. The factual assumptions that underlie this sense of comfort with "routine tests" are frequently inaccurate, and the commitment to autonomy and respect for human dignity that underlies the doctrine of informed consent requires that patients be given the opportunity to make informed choices about every aspect of their care. is Lerman C., Narod S., Schulman K., et ai, "BRCAl testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes", 275 JAMA 1885-9 (1996); Cappelli MSurh L, Humphreys L, et ai, "Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer", 55 Clin. Genet. 419 - 30 (1999), Quaid Κ. Α., Morris M., "Reluctance to undergo predictive testing: the case of Huntington disease", 45 Am. J. Med. Genet. 41 - 5 (1993); Taylor, S. D"Demand for predictive genetic testing for Huntington's disease in Australia, 1987 to 1993", 161 Med. J. Aust. 351, 354-5 (1994).

16 H. L Levy, "Newborn screening by tandem mass spectrometry: A new era", 44 Clin. Chem. 2401-2402(1998). 3*

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only if specific conditions are met: the disease being sought causes serious irreparable harm if treatment begins after the appearance of symptoms, and the harm can be averted only if treatment begins in the newborn period. 17 Yet as often occurs with new technology, both private companies and a growing number of states have adopted TMS, often screening for disorders for which the efficacy of treatment is far less than that for such disorders as PKU and congenital hypothyroidism. In perhaps the most notable recent example, Massachusetts decided to screen for seventeen very rare metabolic disorders on a "pilot" basis.18 Exactly how the outcome of this "pilot" is supposed to be assessed was not made clear. The advisory group concluded that effective therapy for these disorders was already available although these disorders generally are far less amenable to intervention than the disorders most commonly screened for. Perhaps the goal of the pilot project is to assess the technical feasability of finding affected individuals. But meeting that goal fails to meet all the criteria for routine newborn screening for these disorders. The "DNA report card" with a complete genome readout, then, is not an idea whose time has come or that will be here when the technology for widespread testing becomes available. Instead, it will be necessary to assess when specific tests should be incorporated into clinical care, attempting to ensure that the benefits of each test and its ensuing interventions outweigh the potential risks. The fact that blood spots already exist and are readily accessible does not alter the approach that should be taken.

Nor is the time ripe for widespread use of newborn screening samples in research. Just as the pressure to expand newborn screening should not cause the careful consideration of which tests should be performed to be forgone, so too the ease of using already existing newborn blood spots to study interesting biological questions should not lead investigators to bypass asking whether these samples are optimal, or even ethically, legally, and politically acceptable sources of human biological materials for research. Here, as well, the basic desire to study these blood samples is not new. State laboratories have long engaged in research on samples they received and have even shared samples with investigators in other institutions, often simply on the basis of prior relationships and without any review. 19 And it is already known that problems arise when newborn blood spots are used for re17

Committee for the Study of Inborn Errors of Metabolism, Division of Medical Scienc Assembly of Life Sciences, National Research Council, Genetic Screening: Programs, Principles, and Research ( 1975), Committee on Assessing Genetic Risks, Division of Health Sciences Policy, institute of Medicine, Assessing Genetic Risks: Implications for Health and Social Policy 60 - 65 (1994). ι» 105 CMR § 270.006(B)(I999); New England Newborn Screening Program, Optional Screening, http://www.umassmed.edu/nbs/screenings/optional/.

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search. The HIV seroprevalence studies using unidentified blood spots, which were undertaken after a much more formal process of evaluation, still resulted in heated debate.20 In thinking about the appropriate use of newborn screening blood samples in research, it is important to recognize that the issues surrounding research are not the same as those regarding testing. That the use of these samples for research does raise important issues is highlighted by efforts in other areas to be more responsive to ethical concerns raised by research using medical records and human biological materials. Population based studies, such as NHANES, undergo rigorous review and require informed consent.21 The creation of a set of unidentified DNA samples to study single nucleotide polymorphisms (SNPs) underwent extensive discussion and open debate, followed by IRB review. 22 The National Action Plan for Breast Cancer developed a document that permits women to donate tissue left over from their breast cancer surgery for research. 23 This group, which strongly supports research, felt that women want and should have a say in where their tissues go. Tissue repositories all over the country are developing procedures to ensure that tissue samples and accompanying medical information are used in ways that permit valuable research to be conducted while minimizing intrusion on the interests of patients. Given all this activity, it is at best unseemly to use newborn blood spots collected under state mandate for research without oversight or consent, particularly given the extremely limited information that can be gleaned from their use at least with regard to adult onset disorders. Moreover, there is much to be lost by using blood spots for purposes other than those for which they were collected. Newborn screening programs are supported politically because they are designed to help children who would otherwise suffer irreparable harm. The use of newborn blood spots for research regarding the health concerns of adults, such as hemochromatosis and proposals to use blood spots to create DNA report cards could erode that support.

«y McEwen, J. Α., Reilly , P. R., "Stored Guthrie cards as DNA 'banks' ", 55 Am. J. Hum Genet 196 - 200(1994). 2( 1 Kopelman, L M., "Informed consent and anonymous tissue samples: the case of HIV seroprevalence studies", 19 J. Med. Phil. 525-552 (1994). 21 Wagener, D. K., "Ethical considerations in the design and execution of the National and Hispanic Health and Nutrition Examination Survey (HANES)", 103 Environ Health Perspect Suppl 3:75-80(1995). 22 National Human Genome Research Institute, A DNA polymorphism discovery resource, http://www.nhgri.nih.gov/GrantJnfo/Funding/RFA/discover polymorphisms.html. 23 National Action Plan for Breast Cancer, Consent form for use of tissue for research, http://www.napbc.org/napbc/consent.htm; How is tissue used for research?, http://www. napbc.org/napbc/q&a.htm.

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The expansion of testing and other uses of blood spots increase the importance of involving parents. Parents are entitled as a matter of law and of ethics to be involved in making decisions about the health care of their children in all but the most unusual situations. In actuality, most discussions between clinicians and parents are informal, bearing only some resemblance to the ideal of shared decision making so eloquently described by Jay Katz 24 and others. For example, parents may simply be told at their baby's one year checkup, "We need to do a blood test to see if your baby has low iron or too much lead." No further conversation occurs unless the parent asks questions. Nonetheless, clinicians talk with parents not only because they have to in order to treat the child and because they know that the parents will be more "compliant" if they buy into the plan but also because clinicians respect the independent and important role parents play. With a few exceptions, state run newborn screening fails to acknowledge the role of parents. As noted previously, parents are not asked to give their permission for newborn screening and, more often than not, are not even told that it is occurring. The arguments often made to justify leaving parents out of the loop - that newborn screening is a public health matter; that parents would refuse (which they do not), implying that refusal of screening would be actionable neglect; that it would cost too much to talk with parents either to inform them or to seek their permission - are flawed. 25 Analogies to immunizations (for which consent is actually sought26) and life threatening medical neglect, for example, simply do not apply, even for PKU and congenital hypothyroidism, because any particular child is very unlikely to be affected. Even when they do occur, these disorders, while serious, do not threaten the infants' lives or the lives of anyone else. As newborn screening extends to more and more disorders for which the treatment is less efficacious and as pressure increases to use blood spots for research and to create DNA report cards, the practice of excluding parents from the decision making process becomes less and less defensible. The Massachusetts "pilot" project is particularly problematic in this regard. 27 The advisory panel specifically declined to address the issue of informed consent, 24 Jay Katz, The Silent World of Doctor and Patient (1985). 25 E. W. Clayton , op. cit. (fn. 3). 26 Parents, however, are not entirely free to reject immunizations for their children since these shots are required for entry into school in the absence of a medical contraindication or religious objection. 27 A recent recommendation that pilot projects of newborn screening for cysticfibrosis are warranted while routine incorporation is not, demonstrates a similar level of disingenuousness and even cynicism. Newborn Screening for Cystic Fibrosis: A Paradigm for Public Health Genetics Policy Development 46 MMWR No. RR-16, 20 (1997) ("States deciding to implement CF screening among newborns can minimize the cost, particularly that of bloodspecimen collection, by adding CF screening to an existing newborn screening program. The

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deciding instead to send the project to an IRB so that it could decide what, if any, parental involvement was required. This approach appears almost cynical since the current federal regulations clearly would not permit an IRB to waive informed consent for this program. 28 The first requirement for waiver is that the proposal pose no more than minimal risk to the subject. That requirement is not met in this project. Virtually all commentators agree that projects that provide specific results to subjects, as is proposed here, pose more than minimal risk.29 The panel should have acknowledged forthrightly that some parental involvement is required. Even so, Harvey Levy, the "father" of newborn screening for PKU, dissented even from the recommendation to refer the project to an IRB, arguing instead that informed consent should be forgone because it was too hard to obtain. Using blood spots for research in which the results will not be given to the parents in some ways poses fewer problems because fewer individual risks are involved. Nonetheless, almost every group that has addressed the issue of using archival tissue samples has reasoned that using identified or identifiable samples for research requires both IRB review and usually informed consent.30 A growing number of commentators, by contrast, argue that these steps are not necessary (or in the case of permission to use already unidentified samples impossible) when identifiers are going to be removed. 31 Following this line of reasoning, New York's plan to use unidentified blood spots to look for alleles associated with hemochromatosis is legally sound. Defining the circumstances in which it may be acceptable to use newborn blood samples for research depends at least in part on how the newborn screening system is structured. The following guidelines, for example, should apply when samples are collected, as they usually are at present, without disclosure or permission.

process for providing parent education and obtaining consent (if required) should be same as already established for other newborn screening tests within the state. ") (empha added). 2K 45 CFR § 46.116(d)(1999). 29 105 CMR § 270.006(B)(1999). 30

National Bioethics Advisory Commission , "Research Involving Human Biological Materials: Ethical Issues and Policy Guidance", Vol. I Report and Recommendations of the National Bioethics Advisory Commission (1999) (hereinafter NBAC); American College of Medical Genetics , "Storage of Genetics Materials Committee, Statement on storage and use of genetic materials", 57 Am. J. Hum. Genet. 1499- 1500 (1995); American Society of Human Genetics, "Rapid Action Taskforce on Informed Consent for Genetic Research, Statement on Informed Consent for Genetic Research", 59 Am. J. Hum. Genet. 471 - 4 7 4 (1996); Clayton, E. W., Steinberg, K. K., Khoury, M. J., et al., "Informed consent for genetic research on stored tissue samples", 274 JAMA 1786- 1792 (1995); but see American Association of Medical Colleges, "Health data security, patient privacy, and the use of patient archival materials in medical research", http://www.aamc.org/private/deans/afad/deanmemo/dml997/ patpriv.htm. 31 E.g., NBAC, ibid.

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1. The investigators should demonstrate why blood spots are the optimal tissue source for the project. If other samples are available from adults or particularly from individuals who have consented to research, those sources should be used. 2. Projects must be reviewed for scientific merit. If the knowledge to be gained is minimal, then blood spots probably should not be used. 3. Projects should address the health concerns of children. The HIV seroprevalence studies meet this requirement comfortably. A stronger case needs to be made for studying disorders that affect only adults. 4. Unidentified samples should be used unless there are compelling reasons to have continued access to medical records. 5. Where linkages are retained, IRB review is required as may parental permission, samples should be encrypted, and an intermediary identified that can retrieve any further medical information that is needed. 6. Direct identifiers should be retained only in cases of compelling need. In those cases, both IRB review and informed permission are required. Two changes in newborn screening would support broader research use. The Newborn Screening Task Force, for example, recently recommended that new parents be informed about research uses of blood spots and given the opportunity to opt out. 32 The challenge of this approach is to ensure that parents actually receive and understand the information. Legislators might also enact laws specifically authorizing the use of newborn blood samples for research, which would evidence explicit public policy. In either case, care would be needed to minimize the risks to children and their families. Another course would be to collect a representative, population-based set of DNA samples from adults who have given their voluntary informed consent that could be used for research. This strategy would cost the most initially, but it would meet the concerns about lack of consent and the unique vulnerability of children. The opportunity would also exist to collect clinical information at the same time. Such a choice would dramatically increase the associated costs, but such a data set could be used to answer a far broader array of questions than could a simple collection of blood spots. Moreover, a public decision to limit or eliminate the use of newborn blood samples for research and to use them only for the explicit purpose for which they were obtained could sustain political support for these programs by reducing fears of misuse.

32 Newborn Screening Task Force, A blueprint for the future: Recommendations from the Newborn Screening Task Force, draft 10/4/99.

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Zusammenfassung In vielen Staaten werden Neugeborene routinemäßig auf eine Reihe von Stoffwechselkrankheiten getestet, bei denen eine frühe Behandlung eine schwere und lang andauernde Krankheit verhindert. Viele Forscher möchten die Blutproben, die bei diesen Reihenuntersuchungen übrigbleiben, für weitere Untersuchungen nutzen, zum Teil im Hinblick auf Krankheiten, von denen in erster Linie nur Erwachsene befallen werden. Diese Proben können jedoch nur begrenzte Informationen liefern. Darüber hinaus bedroht diese Art der Verwendung der Proben, insbesondere wenn sie ohne Zustimmung der Eltern erfolgt, die Zukunft der Reihenuntersuchungen und widerspricht dem sich herausbildenden Konsens über den angemessenen Gebrauch von humanbiologischem Material für Forschungszwecke.

The Permissibility of Compulsory Genetic Testing Lawrence A. Frolik/ Margaret Gruter

Hypothetical #1 - ABC Genetics The ABC Genetics Testing Corporation (ABC), has developed a test to identify two genes associated with breast cancer. The test indicates whether the genes carry a mutation. Epidemiological studies indicate that women who carry both these mutated genes have significantly higher rates of breast cancer. Although the figures are somewhat in dispute, it appears that the possibility of contracting breast cancer before age 60 increases by 40% if a women is a carrier of both mutated genes. The onset of breast cancer prior to age 60 is particularly important because death rates are much higher in younger women. Although ABC claims its genetic test reveals a 40% higher incidence of cancer, some researchers claim that the rate is actually between 20 and 40% with environmental factors being responsible for the variance. There is some evidence, for example, that women who live near large quartz deposits are exposed to higher radon levels, which may trigger breast cancer if they carry the double mutation. ABC already markets the gene test to the public. Micro Hard, a leading computer software manufacturer, employs nationwide over 10,000 women between the ages of 25 and 60. Micro Hard proposes to have every female employee take the ABC gene test at its expense. Micro Hard hopes that the use of the test will enable its female employees to have a better understanding of breast cancer and to take appropriate responses, including more frequent physical examinations and more aggressive treatment of any indications of potential cancer. Micro Hard also believes that if environment contributes to the onset of cancer, female employees can modify their behavior to reduce environmental risks such as modifying their diet or avoiding possible sources of radon. While Micro Hard is concerned about physical well-being of its employees, it frankly admits that if it could lower the incidence of breast, it would lower its medical costs. (Micro Hard is a self-insurer, meaning that it pays its employees' medical expenses and does not use a thirdparty insurer.) The question is whether Micro Hard should be permitted to require all of its female employees to take the test. Further, having taken the test, must employees be told of the information? That is, could the employee submit to the test, but refuse to learn the test results?

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Discussion of Hypothetical #1 ABC Genetics and Micro Hard The proposed genetic screening that would reveal a propensity for breast cancer is fraught with conflicting interests. Micro Hard's concerns arise from its dual capacity as employer and health care insurer. While the interests are in the main congruent, at the margin, the interests of an employer can diverge from the interests of a health care insurer. Of course, whenever the interests of the employer and insurer conflict, the employer's interest will prevail. The employees may also have conflicting interests. As employees, they have an interest in maintaining their health in order to maximize their ability to work and to earn. Yet the employees are also individuals with interests and goals that differ from that of an "employee". For example, the female employees are also spouses, mothers, lovers, grandmothers and even adult children. Each of these roles places different demands upon the individual from which may flow quite divergent values and personal interests. In to these personal roles, each individual is a member of one or more communities including society at large, but also more particularized communities such as churches, social clubs and political action groups. The crosscurrents of values may produce conflicting goals for each employee as well as conflict with the needs of their employer, Micro Hard. Finally, theories of evolutionary psychology inform us that individuals are motivated by deeply held biological and reproductive drives that significantly influence behavior even without conscious awareness. The employees may act in a manner that appears irrational unless we recall that they may be governed more by reproductive instincts than a rational desire to promote their own self-interest. If Micro Hard is willing to pay the cost of the genetic test, it must believe that the value of the test exceeds the costs. While Micro Hard may be acting altruistically and paying for the test solely to benefit its employees, the better assumption is that it is primarily interested in maximizing its economic well-being. The economic benefits to Micro Hard relate to its dual roles as employer and insurer. As an employer, Micro Hard values healthy employees. Unhealthy employees are less productive, miss work and if they become too ill, must be replaced. New workers cost Micro Hard in recruitment and training costs. Sick employees are also a distraction for other employees and lower morale of the other employees. For Micro Hard , the genetic test should realize cost savings by lowering the incidence and virulence of breast cancer in its employees. Ancillary benefits include the probability that women who carry both mutated genes may be more actively involved with their general health care even though not related to cancer, which may result in better prevention of other physical ailments including earlier detection of other forms of cancer. Those with the double mutation can be expected to show greater concern with proper diet and even adopting a healthier lifestyle. Women who do not have the double mutation may also be more alert to the possibility of breast cancer and other ailments and may also be more aggressive in seeking out preven-

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tive health care. In short, the test may have female (and even male) employees to the salutary benefits of preventive health care. An ancillary benefit may be the appearance that Micro Hard is a caring employer who is willing to use the latest technology to benefit its employees. Micro Hard's interests as an insurer also include possible lower costs of health care reimbursement if early detection of breast cancer results in less expensive treatment of the disease. The testing can be expected to increase the female employees' general use of preventive medicine, which should result in lower health care costs. Some aspects of the genetic testing, however, may not prove cost effective. Women who carry the double mutation, but who do not have breast cancer, may be reluctant to change employers if the mere existence of the double mutation must be revealed to any potential new employer. The higher probability of breast cancer might cause some potential employers to refuse to hire the applicant for fear of incurring the economic and human costs of later having an employee with breast cancer. If the detection of the double mutation results in women who test positive not departing Micro Hard at anticipated rates, the company would incur greater medical care costs. The interest of the female employees are more complex. The genetic test is valuable to the company because of its statistical probability, not because it predicts the future for any particular employee. For the employee, however, the statistical probability for the group is meaningless. The test of the double mutation tells the employee that she has an increased likelihood of breast cancer, but the increase is only 20% to 40%. Far from a certainty. If an employee does carry the double negative, how should she respond? She can do little to decrease the likelihood of breast cancer, other than avoiding possible environmental triggers, such as living near quartz deposits. She can also have frequent checkups (note that this increases the cost to Micro Hard), but doing so will only detect and not prevent cancer. Even if she does not carry the double mutation, however, a wise female employee would have frequent checkups and avoid environmental triggers of cancer. The test, in a word, only has value if it causes the employee to take greater care with her health. But if she is already a conscientious individual, the test has almost no value. If positive, she should continue her healthful behavior. If negative, she should still continue her healthful behavior since even women without the double mutation suffer breast cancer and healthful behavior can prevent other ailments. This is the paradox of the individual versus group response to information. In theory, the female employees have no reason to take the test, since it should not affect their behavior. Rationally, each should treat their health in an optimum manner regardless of whether they have the double mutation. As a group, however, we can predict that at least some employees, as a result of testing positive, will take better care of themselves, thus lowering medical costs for the employer. Even some women who tested negative may have their consciousness raised and take better

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care of themselves. Just as screening of employees for high cholesterol readings heightens everyone's awareness of the need for health diets, so can a genetic breast cancer test alert women to the need for frequent examinations and the like. In fact, the test would be valuable even if it were a fraud. As long as the test, valid or not, encouraged the women consider the dangers of breast cancer, it would be helpful to the insurer. So we might ask whether the test (which in this hypothetical is valid) has any negatives for the female employees? The answer is yes to the extent that a positive outcome creates stress. For some women knowing that they are at higher risk of breast cancer will be dispiriting news. Any gain from being alerted to the possible danger will be offset by the psychological and emotional cost of worry and despair. If the individual is sensitive enough, the psychological strain may translate into injury to the immune system. As a result, the woman might be more susceptible to infections and illness. She might even be more likely to contact cancer. The genetic test might perversely help create the very condition that it was suppose to help avoid. The test may also engender misunderstanding. No matter how carefully the test results are explained, some of the tested employees are likely to misapply the knowledge. Women who tested negative might gain false confidence and fail to watch carefully for early signs of breast cancer. Those who test positive are likely to equate a higher probability with a certainty of breast cancer. The words, "breast cancer" are so frightening that no matter what they are told, some of the women who test positive for the mutation will over react and over estimate their probability of suffering breast cancer. Some whose mothers or other relatives had breast cancer may reasonably assume that they are at much greater risk than the average woman with the double mutation. Conversely, others will refuse to believe the possible bad news, rejecting it as mere speculation. Whatever the reaction, there is no reason to believe that all the employees who test positive will calmly and rationally accept the information. For the individual, the news is not a statistical occurrence, but a possible personal tragedy. For those who test positive, there are further consequences. Recall that the female employees function in many other roles: mother, wife, lover, and the like and are members of many different communities. In each of these roles the news of being a carrier of the double gene has potentially negative connotations. Imagine that a 32 year old employee tests positive. She is married, but has no children. She now knows that she has an elevated chance of breast cancer. Consider her difficult choices. Should she tell her husband? If she does, it may undermine their relationship (or it could strengthen it?) Should she hesitate to have children for fear of leaving them without a mother should she die of cancer. Should she quickly have children before she contracts cancer? If she has the genetic mutation would her daughter also carry it? If so, should she abort female fetuses? Should she tell her 55 year old mother to be tested for the mutation? Her sisters or cousins?

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What of a 25 year old woman who tested positive and whose mother died at age 47 from breast cancer. Should she tell the man she is living with and expects to marry of her positive test? Should she go to law school as she had planned or is that a futile waste of precious time? How about the 43 year old positive testee who is divorced, but hoping to remarry. How will this information affect her attitude toward dating and possible remarriage? What should she tell a possible marriage partner about the test? Assume a 58 year old grandmother tested positive. She is not worried about her 37 year old son, but what should tell her 16 year old granddaughter? Should she take early retirement as she had planned or should she continue working to insure adequate health care insurance. The scenarios are almost without end and all suggest the personal cost of learning of negative information about which little can be done. Unlike being told of high cholesterol, to which there is a rational and effective response by changing diet or taking a medicine to lower it, being informed of this genetic marker does not alert the women to do anything that they would not otherwise have done, unless we assume that they would not have taken sensible preventive medical care in the absence of this test. The varying and possible negative consequences to the women, suggests that the value of the test is almost solely for the employer. Whether this leads to the conclusion that ethically the employer should not be permitted to mandate the test, and perhaps not even suggest it to the employees, depends on whose interests are considered primary. Arguably, employers should not be permitted to use their position of market power to advance their interests at the expense of the employees', even if the action is ostensibly for the benefit of the employees. Societal interests, however, may suggest otherwise. Presumably, society has an interest in the health of the Micro Hard employees. (The interest arises from concerns about economic efficiency, worker productivity, health care costs, and even in the happiness of the employees - better health being equated with happiness.) If it is true that the use of the test will encourage the women to seek better preventative health care, then despite the psychological costs to those tested, society would realize a net gain if the women collectively would realize an increase in utilities or happiness. This assumes that the early detection and prevention of breast cancer has extremely high value to the individual, whereas the injury of each individual who suffers psychological injury is comparatively small. Thus the interest of the few arguably should prevail over the concerns of the many. The ethical dilemma is correctly seen not as a binary Micro Hard versus female employees, but as a more complex triad: society - Micro Hard - employees - with each of the three having conflicting interests that prevent a measurable set of values or a unified response. There may be no overarching ethical answer, but only a set of responses, each of which merely advances the interests of each of the actors while acknowledging their unavoidable conflict of interests and values. "Hard"

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questions in genetics will often present themselves not as clear individual ethical choices, but choices presented in a complex and seemingly chaotic environment. Institutions and individuals will act pressed by time and a lack of understanding of the consequences of their actions. Consequently, ethical considerations are likely to be considered secondary to concerns about immediate apparent self-interest.

Hypothetical #2 - Biosis A new corporation, Biosis, believes it has identified a series of genetic markers that indicate the potential life-span of an individual. To test its theory, Biosis, approaches the United Automobile Workers Union (UAW) with the following proposal. Biosis will select randomly 2,000 members of the Union and take a blood sample of each member to identify the suspected genetic markers of longevity. Biosis will then undertake a longitudinal study of the tested UAW members to determine whether the genetic markers predict life expectancy. At the present, Biosis has no plans to attempt to modify these markers to extend life expectancy. Their interest is solely in whether these markers have predictive value. The question for the UAW is whether it should permit its members to participate in such a research project. The UAW learns that Biosis is being funded by a consortium of life insurance companies. The UAW Board of Directors is meeting to discuss whether to approve the participation in the study. Should they?

Discussion of Hypothetical #2 Biosis and the United Auto Workers This case raises the question of the ethical obligations of those acting in a fiduciary relationship. The UAW Board must weigh the value of the study to society and indirectly to their members against the cost to the individual members who participate in the study. The question, of course, is assuming genetic markers of longevity exist, whether the participants will be informed of what their markers predict. At first blush, it may seem that the easy answer is not to reveal information of genetic marker predictions to individuals. Indeed, it might seem cruel to do so. But what if an individual, perhaps because of his or her family history, anticipates a short life expectancy and demands to know the test results. Should the information be released? If it is, does that not place pressure on others to know the results of their genetic markers? And what of insurance concerns - both life and health? Can the UAW Board simply decline to approve the test or should it poll its members? Is this the kind of question that is susceptible to a majority vote? Or is the UAW Board empowered to consider and answer the ethical issues on behalf of

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its members? Can the issues be fairly understood by the members or is this the kind of complex moral issue best decided by a smaller governing body? Of course, the Board was not elected by the members with any anticipation that it would be called upon to respond to ethical questions of this sort. Arguably, the Board should pass on the request because it lacks the expertise or the legitimacy to make such a decision on behalf of the membership. This supposes, of course, that ethical questions raised by genetic research are of such a different nature from other ethical questions posed to the UAW Board, that the Board cannot responsibly address them. That seems improbable. Yet the individual Board members might well believe that they lack the authority to answer genetic research requests. If the Board should conclude that the research might be counterproductive for some of its members, can the Board refuse to permit the Union to participate? To refuse would place the Board's loyalty and obligations to its members above its duty to help promote societal interests in general - assuming that the test would further societal interests.

Hypothetical #3 - Sanguine A biotech corporation, Sanguine, Inc., has developed the capability of modifying in vitro, certain genes which apparently contribute to a mild form of depression that is experienced particularly by adolescents between the ages of 12 and 18. This adolescent angst, which was formerly thought merely to be a normal part of maturation, has now been identified as mild form of depression, which can be alleviated by the use of Prozac or other prescribed drugs. Most, but not all individuals, stop experiencing the depression by age 20. Untreated depression in adolescents leads to antisocial behavior, increased drug and alcohol abuse, and a higher incidence of suicide. Most teenagers who experience depression are not treated, but those who have been treated with prescription drugs report an increase in contentment, significant reduction in alcohol and drug abuse, a lower rate of suicide, better socialization with peers and elders, and more success in life activities. Sanguine has learned that 60 to 80% of all individuals are born with the gene combination that makes them susceptible to a form of adolescent depression. Only 50% of individuals who carry those genes experience adolescent depression, however. The reason half do not experience depression is not understood, but it is thought that environmental factors or family structure plays a role. Sanguine asks to be allowed to market the genetic alteration procedure to prospective parents. Drug companies who sell Prozac and other antidepressants object to Sanguine's marketing plan. They argue that because drugs relieve the depression, there is no need for the genetic alterations. 4 Jahrbuch für Recht und Kihik, Bd. 9 (2001)

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Should we permit Sanguine to enter the market with its genetic alteration therapy?

Discussion of Hypothetical #3 Sanguine modification of genetic basis for adolescent depression This case illustrates the tension between market solutions and regulation. That is, should we permit the market to determine which therapy to favor or should the government act as a gatekeeper? The advantage of the use of antidepressants is that they can be used only when needed. Genetic alteration in this case would be unnecessary in at least half the cases (if not more.) If the market would favor genetic therapy that may result in a misuse of resources. The impetus for genetic therapy will be those parents whose inherent biological parental reproductive interest in healthy offspring (whether conscious or merely a deeply held feeling that motivates what the parents believe is "doing best for their children") will almost certainly impel them to insist on drug therapy at rates higher than a more rational measure of cost / benefit analysis would warrant. (It is irrelevant whether the parents pay for the gene therapy or shift the cost to medical insurance companies.) From a societal viewpoint, drugs may be an adequate manner of lowering the rate of adolescent angst. From an individual parent perspective, genetic intervention may appear justified. The ethical issue cannot be addressed without an initial determination of whether the individual parental rights must be respected regardless of the cost to the larger society. Alternatively, can society bar genetic engineering in favor of individualized drug treatments in reliance on the statistical truth that in terms of the group, drugs are more efficient that genetic treatment?

Zusammenfassung Angenommen, ein genetisches Test verfahren, das in der Lage ist, eine Veranlagung zu Brustkrebs zu ermitteln, wird einem Arbeitgeber von 10.000 Arbeitnehmerinnen angeboten, der Selbst-Versicherer ist. Sollte es dem Arbeitgeber erlaubt sein, dieses Testverfahren seinen weiblichen Angestellten anzubieten oder sogar von ihnen zu verlangen, sich dem Test zu unterziehen? Die Arbeitnehmerinnen könnten indes Interessen haben, die insoweit mit denen des Arbeitgebers konfligieren. So haben Arbeitnehmerinnen durchaus ein Interesse daran, ihre Gesundheit zu schützen, aber sie sind auch Individuen mit Interessen und Zielen, die von denen eines „Arbeitgebers" abweichen. Jedes Individuum ist Mitglied einer Familie und von einzelnen Gemeinschaften, wie Kirchen, Vereinen und politischen Aktions-

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gruppen. Die sich überkreuzenden Werte können sowohl konfligierende Ziele jeder einzelnen Arbeitnehmerin hervorrufen als auch zu Konflikten mit den Bedürfnissen des Arbeitgebers führen. Darüber hinaus wissen wir aus den Theorien der evolutionären Psychologie, daß Menschen von tief verwurzelten biologischen und genetischen Antrieben motiviert werden, die unser Verhalten signifikant beeinflussen, auch ohne daß uns dies bewußt wäre. Die Interessen der weiblichen Arbeitnehmerinnen sind komplexer Natur. Wenn eine Arbeitnehmerin das betreffende Gen hat, wie soll sie reagieren? Ist es besser für sie, davon zu wissen, oder ruft dieses Wissen unangemessenen Streß hervor? Nicht alle Arbeitnehmerinnen, bei denen der Test positiv ausgefallen ist, werden diese Information ruhig und rational akzeptieren. Für einige beispielsweise wird sich diese Information in hohem Maße zersetzend auf ihre persönlichen Beziehungen auswirken. Das ethische Dilemma, das sich hier auftut, besteht aus einer komplexen Triade: Gesellschaft - Arbeitgeber - Arbeitnehmer, von denen jede der drei Seiten konfligierende Interessen hat, die einen vergleichbaren Wertekanon oder eine einheitliche Reaktion verhindern. So könnte es sein, daß es keine alle Differenzen überbrückende Antwort gibt, sondern nur eine Reihe von Antworten, von denen jede lediglich die Interessen eines einzigen der beteiligten Akteure begünstigt und dabei deren unvermeidbaren Konflikt von Interessen und Werten lediglich anerkennt.

Genetic Data Banks Lorenz Schulz

Starting case* In an island state, parliament decides to improve the health of the island people and at the same time to serve scientific research by means of a central data base, in which all medical and genetic information of the island people is to be registered. The data base will firstly serve the analysis of hereditary diseases. The island people are especially suitable for such analysis due to their genetic homogeneity (due to isolation) and small variations in the gene-pool. Furthermore, the medical data of most of the population have been completely recorded for the past 80 years. The plan is to obtain the genetic information of every island inhabitant. Because the state has limited resources it passes the task to a commercially organized firm, which is able to invest the required 200-350 million DM. The firm therefore will have exclusive usage rights.

Questions 1. Is the establishment of the data base by private handling of the data base permitted, considering especially constitutional law? 2. May the data base be used at some time for the purpose of public prosecution?

I. Case Background "Lose your dreams and you will lose your mind" (The Rolling Stones, "Ruby Tuesday")

In earlier centuries, this case easily could serve as part of a Utopian model of communal life, be it an optimistic eu-topia or a pessimistic dys-topia. To choose an island meant choose a setting without a location in the real world (u-topos). As the * I thank Agust Thor Arnason, Ragnar Adalsteinsson and Sigurdur Ingvarsson for their assistance.

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dream comes closer to realization, one may suppose an actual location in place of that misty Atlantis.

/. General features The case has left the realm of Utopian tales. Already in the mid-seventies, the government of the island of Iceland considered the idea of a centralized data base. It then took some years of technological progress until this case became widely discussed in Iceland. On March 31, 1998, the Icelandic Minister of Health introduced in parliament (the Althingi) the first draft of a bill proposing the establishment of the aforementioned data base to contain the genetic heritage of the Icelandic population. By the end of 1998, there were three drafts and, as a sort of Christmas gift to the people of the island, a bill was passed on December 17, 1998. The vote was 37 to 20 with 6 abstentions. Opinion polls, both formal and informal, confirmed that this rather clear vote indicated general support of the bill. While the discussion in parliament came to an end, popular discussion remained lively. This is another result of dealing with reality instead of utopia. Whereas in a Utopian narrative it is typical that the island remains isolated, the contrary is true in this case. The global discussion soon dominates the local one. Although the case is not to be read as a fairy tale, this advantage is similar to Utopian narratives. It serves the global discussion on data bases by offering a clear test case. The establishment of a national medical data base that includes the genetic data of a population concerns every nation since it results inevitably as a matter of universal technical progress. There are various advantages of medical and economic kinds, as the Icelandic discussion demonstrates. The Icelandic legislature noted four categories of benefits of such a data base1: 1. "acquisition of new knowledge on health and disease, 2. improved quality and economy in the health system, 3. development of high-technology industry in Iceland and thus employment for a highly-educated sector of society, 4. potential for attracting to Iceland business relating to the database." Since the opportunity to improve healthcare, a sufficient motive in itself, is indisputably great, collecting and storing detailed personal health and genetic data will become a matter of course. Therefore, the point of departure for the debate in practice is the question why one should not establish such a data base. Since one hardly can argue against a data base as such, the debate has to focus on modalities.

1 For more information on these advantages see the homepage of Decode Genetics (http:// www.database.is).

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2. Homogeneity? That the Icelandic heritage seems to be a true genealogical gold mine gives the case a special appeal. This population is famous for its relative genetic homogeneity although this may turn out to be a lucrative tale. Founded a millennium ago by Norwegian settlers, the island has been more or less isolated from the genetic variety of the rest of the world. In some way, everyone is a relative of his or her neighbor. In addition, Icelanders have been inclined to collect data on themselves relevant to their cultural identity and to health issues. The medical data of most of the population have been completely recorded for the past 80 years. Moreover, the collective identity of Iceland is built on the genealogical historiography, the historiographical principle of genealogy, which as many other European countries in the Middle Ages was legally important for claims to property and political power. This principle is illustrated most prominently in the preservation of parental first names in individual family names2. In some cases, this genealogical narrative goes back to the founding fathers, and in the majority of cases it goes back at least several centuries. Families kept their own records, and the churches kept the official ones. The genealogy of at least 750 000 inhabitants that lived on the island from the first settlement onwards appears to be almost completely recorded 3.

3. Business as usual? A second element of interest is the overt entanglement of Government with business. "Business as usual", does this maxim hold even for the aforementioned gold mine of a homogenous population? The case reflects a common sequence in modern economics. First comes a profitable idea, second a strong company, and third persistent lobbying. In this case, two neurologists from Harvard Medical School, Karl Stefânsson and Jeff Gulcher, come across the idea. In 1994, during research on the population genetics of multiple sclerosis (MS), they discovered the mentioned gold mine. To exploit it they decided to found a corporation. The company was established in August of 1996, in the state of Delaware for tax reasons, and named Decode Genetics. The original investors of Decode are mostly American

2 On this principle in the High Middle Ages see Gabrielle Spiegel, "Genealogy. Form and Function in Medieval Historical Narrative", in: History and Theory 22 (1983), 43-53. 3 By the end of 1999, already 600 000 of them are supposed to be in data bases; Barbara Supp. "Der Rohstoff Mensch", in: "Spiegel Reporter" 01/2000, 82 ff, 87. The total number of 750 000 is a matter of counting; the figure as well may reach 1 million according to a different way of counting; for information, I thank Sigurdur Ingvarsson, National University Hospital, Reykjavik. For a severe criticism on the homogeneity thesis see Einar Arnason et ai. Genetic homogeneity of Icelanders: fact or fiction? in: Nature Genetics 25, August 2000, 373-374.

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venture funds 4. A wholly owned Icelandic subsidiary was established, and with $ 12 million the company started operations in Iceland. While it had 45 employees by the end of 1997, it gained more than 300 by mid 2000. For the small country of Iceland, this is an eminent growth of employment, 350 high-paying jobs is comparable to 350,000 high-paying jobs in the US 5 . The company sold an additional 2 million shares to Icelandic investors at $ 5 per share, and those were traded in 1999 at more than $ 20 per share, establishing the market value of Decode at almost $ 500 million. Stefänsson, a tall, energetic personality with Calvinist-like charisma was nominated in the magazine "Red Herring" in 1998 as one of the world's top 10 entrepreneurs. He seeded his idea in 1997. By the end of that year the Minister of Health had decided to back the idea by swift proposal of a bill. In February 1998, a Swiss corporation, the global corporation Hoffman-La Roche, informed the public of an agreement with Decode for a five-year-collaboration focusing on the discovery of specific genes. "This agreement", the media release of Feb. 2, 1998 goes on, "could lead to potential payments by Roche in excess of 200 million US dollars over those five years, in the form of equity investment, research and milestone payments and royalties". Part of the agreement is a gift to the Icelandic people, namely the free provision of certain pharmaceutical and diagnostic products emerging from that collaboration. In return, "Roche has exclusive rights to develop and commercialize pharmaceuticals and diagnostics with the exception of antisense and gene therapy products". Notably, the Act explicitly states the authorization to use the data "for purposes of financial profit". In economic terms, some observers regard the deal as square for Iceland as well, because the aforementioned goldmine relates in its value to competing mines in other countries which may be detected soon6. Whether this story of Decode will be a success story in the long run has been questionable. By fall, 2000, a considerable number of Icelanders had withdrawn their permission to use their medical data for the data base (for the possible refusal see below). Both the Iceland Medical Association and the World Medical Association Council have opposed the data base7. Therefore, a significant number of Icelandic physicians may not be sending their patients data to the data base unless they 4

The company issued 20 million shares and sold 12 million to a group of seven American venture funds at $ 1 per share. 5 Cf. Bernhard Palsson/Snorri Thorgeirsson, "Decoding developments in Iceland", Nature Biotechnology 17, May 1999,407. They participated in founding a competitive Icelandic biotechnological company. 6 Thus, American Indians or Ashkenazim are the target of genetic research. 7 See Nigel Duncan, "World Medical Association opposes Icelandic gene database", British Medical Journal 1999, 318:1096 (24 April). The objection rests on the following grounds: 1. Invasion of privacy, 2. Breach of patient/physician trust, 3. Lack of independent review mechanisms, 4. Abuse of patient consent, 5. Disregarding of established scientific standards, 6. Use of medical records as a commodity, and 7. Creation of a centralised database of an entire population.

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have a written request from the patient. Of course, if such refusals are considerable in number, the data base will not be effective. Last but not least, "Mannvernd", an association for ethics in science and medicine, has filed a complaint with the EFTA Surveillance Authority questioning the bill based on its infringement of monopoly agreements that Iceland is party to as part of the EEA Agreement (see below)8. Since the establishment of the data base is without precedent the solution is challenging. There is no violation of Icelandic law as long as there is an obligation to provide a service fulfilling certain essential needs of a population. This could well be the case although the data base is not like the distribution of gas, the postal service or a transport service for purposes of precedent. This is by and large a normative issue. In the end, the data base did match the "necessity test". In any case, the broad discussion continues9. To answer the questions raised by the case eventually will require a look at the relevant concrete legal concepts, i.e. Icelandic law on the health sector data base. At the same time, the constitutional framework of this law has to be considered. Since this framework leads to ethical questions, they have to be addressed as well. The analysis would not be adequate without the sociological aspect of increasing control.

II. Control society - sociological and philosophical aspects The case illustrates the enormous potential of control created by modern technological improvements. Although paradoxically accompanied by increasing security in many everyday life aspects, risk society is risky because of the proliferation of communication and free floating information. Governmental as well as private agencies already collect a tremendous and still increasing amount of information. Therefore, to give just one instance, the once popular phenomenon of fraud in the field of social security is reduced. In general, as any bodily action results in almost invisible remains eligible for DNA-analysis, so any move in the digital arena of the world-wide web is recorded - a virtual gold mine provoking "data-mining" and "data-trading". Genetic data are paradigmatic in value. Interestingly, the EU directive on the protection of personal data exempts genetic data from those not be used in principle (art. 8 para. 1). This directive is, for the EU and for "European Economic Area" (EEA) countries like Iceland, the point of departure for any kind of

« The complaint dating from 28 April 1999 claims abuse of a dominant position according to art. 59 of the EEA agreement combined with art. II and 12 (technical barriers to trade), art. 36 (freedom to provide services) and art. 54 (abuse of a dominant position); see http:// www.mannvernd.is/english/articles/mv.efta.complaint.html. As a matter of course, the condition stated in art. 54 (1) - effect on trade between the Contracting Parties - is fulfilled. Decode intends to be a "global player". ^ For the coverage of the national and international discussion see the homepage of Mannvernd (fn. above), of Decode (see fn. 1) and of the companies, institutes at Berkeley and Reykjavik (http://sunsite.berkeley.edu/biotech/iceland).

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future action concerning personal data 10 . One of the reasons is the advantage for individuals, e.g., to give evidence of their innocence in a criminal case. Thus genetic data may be safeguarded only in combination with health aspects. Besides the individual advantages, there are vague collective interests. They embrace public and private interests, as the Icelandic case illustrates paradigmatically, raise the sociological issue of control. Data protection is just not very popular. That can be observed globally 11 . In the US, the "Genetic Privacy Act", a proposal for federal legislation dating from 1995 and growing out of the ELSI activities, hardly reached a committee of U.S. Congress so far. Because of the minor interest in privacy protection, this result likely would have happened even without MonicaGate. The prospect for genetic privacy bills does not look better in the near future. The use of genetic data increases the potential of injuries to individual rights. Global commerce gives this increase a specific momentum. The potential of injury opened by a data base of the Icelandic sort is illustrated by the famous legal conflict between the University of California, an L.A. located genetic institute and the Sandoz Pharmaceutical Corporation on the one side and John Moore at the other. Moore's blood was a true gold-mine for the participants, except himself, providing them with a number of lucrative patents. Moore was not eager to prohibit the use of "his" data but to get an adequate share of the profit. So far, the US Supreme Court has not addressed the question of genetic data property rights. The sociological approach to control shows high risks of the digital revolution of traditional life. Surveillance and punishment ("Discipline and Punish: The Birth of the Prison"/"Surveiller et Punir", originally 1975) is the key of the classic approach Foucault's to increasing control. However, the late Foucault himself retreated from the idea that control itself means manifest or subtle force. His analysis leaves the focus of the sovereign state and societal discipline and concentrates on "gouvernement" as a third dimension of power 12 , detecting the ambivalence of the modern self controlling subject. Contrary to his earlier concept, not every technical skill and not every communication is a phenomenon of power. There is also a pro-

10 Iceland is one of the 40 members of the European Council and, like Norway, a member of the EEA, which is closely allied with the European Union. For the German translation of the "EU-Datenschutzrichtlinie" see the Amtsblatt der EG, Nr. L 281 / 31, Nov. 23, 1995. It also can be found at http://www.datenschutz-bayern.de/recht/eu-datensch.htm; for a commentary on it see Ulrich Dammann/ Spiros Simitis, EG-Datenschutzrichtlinie. Kommentar, Baden-Baden 1997. Only five out of the 15 EU member states were able to transform the directive into national law within the given three years (Greece, Italy, Portugal, Swede, Great Britain). Germany is not among them; at least, out of the 16 states of the Federal Republic of Germany, Hessia was able to do so on Oct. 28, 1998, confirming its almost legendary status of being the pioneer of data protection in Europe. 11 For Germany and Europe see Spiros Simitis, "Die Erosion des Datenschutzes". Von der Abstumpfung der alten Regelungen und den Schwierigkeiten, neue Instrumente zu entwickeln, in: Bettina Sokol (Hg.), Neue Instrumente im Datenschutz, Düsseldorf 1999, 5 - 40. 12 Susanne Krasmann, "Regieren über Freiheit. Zur Analyse der Kontrollgesellschaft in foucaultscher Perspektive", Kriminologisches Journal, 3/1999, H.3.

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cess of discursive approximation to truth depending on the exclusion of force . Power may be distinguished from a legitimate "état de domination", that does not involve overwhelming actors but freedom based on fair play between actors. With reversibility of this play as criterion of legitimacy Foucault introduced a normative element into his analysis14, opening it eventually to refinement in law and practical philosophy. The point of departure in this analysis is freedom as freedom of communication. This is opposed to a "socialist" concept of collective property of sensible data as well as to an "individualistic" concept not acknowledging that the individual is born in society and not in void. Privacy is not a concept that can be handed over to anthropology or sociology. To cope with it, one needs normative grounds provided by law and practical philosophy15. The main market where both of them meet and trade their concepts is constitutional law that, therefore, is to be analyzed in the beginning.

III. Constitutional Law Looking at the case from constitutional law there is the question of human dignity. In many modern constitutions, human dignity is a key element16. The same is true of the supra-national constitution at the European level or at the level of the United Nations and specifically of the German constitution ("Grundgesetz", GG) 1 7 . In art. 1 GG, human dignity functions as the primary constitutive principle, constitutive especially for human rights1 x . Therefore, dignity at least is to be deter"Prozess kommunikativ-diskursiver Annäherung an 'Wahrheit', der gerade von der Ausblendung von Machtansprüchen abhängt"; Thomas Gutmann, "Nietzsches 'Wille zur Macht'" im Werk Michel Foucaults", Nietzsche-Studien Bd. 27, 1998, 377 ff., 416. 14 Gutmann, ibid. (fn. 13)418. >5 The normative "kit" between the private and the public, the individual and society, may be analyzed by the category of responsibility. Of course, the specific form of being responsible varies considerably from society to society, from culture to culture, from period to period in history. Despite this variety, there are structures of responsibility determining in a certain way even the solution of the Icelandic case, mediated through ethics and law; see L Schulz, Verantwortungsstrukturen in Recht und Moral, in: L. Schulz (ed.), "Verantwortung zwischen materialer und prozeduraler Zurechnung". Beiträge zum Kolloquium des Jungen Forum Rechtsphilosophie am 1. Okt. 1998 in Frankfurt am Main, Stuttgart 2000, 175 ff. (ARSP-Beiheft 75). 16 In Greece, 1975 dignity is constitutionally introduced in the name of the trinity that stood at the beginning of the Code χ Justinianus. More recently, Spain and Portugal followed in introducing dignity as key element. Apparently, the Icelandic Constitution, revised in 1995, follows the European standards; I thank Ragnar Adalsteinsson for information on it. 17 Art. 1 General Declaration of Human Rights ; art. 1 European Basic Rights Charta (Dec. 7, 2000). is For the jurisdiction see BVerfGE 6, 32 (36: "tragendes Konstitutionsprinzip") (= "Elfes"). Among the overwhelming literature see Wolfgang Graf Vitztum, "Gentechnologie

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mined by reference to basic individual rights19. As far as there are specific applications of this principle - either individual rights or objective sub-principles or rules - the point of departure is these applications. In German doctrine, this is, for the purpose of this analysis, a part of the general right to act freely ("allgemeine Handlungsfreiheit"), the so-called "allgemeines Persönlichkeitsrecht" 20, usually cited together with the principle of human dignity (art. 2 para. 1, art. 1 para. 1 GG). Literally translated, it is the "right of general personality" 21. Its meaning, however, is mainly co-extensive with the right of privacy 22 . Since this right is a special case of and Menschenwürdeargument", in: Ulrich Klug /Martin Kriele (ed.), Menschen und Bürgerrechte, ARSP-Beiheft 33, Stuttgart 1988, 119 ff., and, more recently, Ludger Honnefeiden "Humangenetik und Menschenwürde", in: Thomas Β rose/Matthias Lutz-Bachmann (ed.), Umstrittene Menschenwürde, Beiträge zur ethischen Debatte der Gegenwart, Hildesheim 1994. Honnefelder convincingly points out that it is not the genetic program that constitutes human dignity for the human genome consists of amino-acid structures which are almost the same as those of apes, i.e. primates (169). See also Ulf rid Neumann, "Die Tyrannei der Würde. Argumentationstheoretische Erwägungen zum Menschenwürdeprinzip", ARSP 1998, 153 ff. (non-ontologically founding human dignity on a mutually recognised demand for respectful treatment of other human beings and advocating a minimal reference to the argument of dignity). In traditional Scholastic terminology, dignity is an ascriptive esse morale; Theo Kobusch, "Die Entdeckung der Person. Metaphysik der Freiheit und modernes Menschenbild", Darmstadt, 2. (mit einem Nachwort versehene) Aufl. 1997; for the rise of the modern notion of dignity see also L Schulz (fn. 15). 19

See Eric A. Hilgendorf, "Die mißbrauchte Menschenwürde", in: Jahrbuch für Recht und Ethik (Annual Review of Law and Ethics 7 (1999), S. 137 ff.; Neumann (fn. 15); Horst Dreier, "Die Kategorie der Verantwortung im demokratischen Verfassungsstaat", in: Neumann/L. Schulz (Hg.), Verantwortung zwischen Recht und Moral. Referate der Tagung der Deutschen Sektion der Internationalen Vereinigung für Rechts- und Sozialphilosophie vom 2. bis zum 3. Okt. 1998 in Frankfurt am Main, Stuttgart (ARSP-Beiheft) 2000. 2 ζ tut a

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{1}

[12]

ι- (We) : (z,a). R0za

6,1 IT

{1}

[13]

(We) : (z,a). R o z a ι ζ tut a : νRoZoao

I2T

{1}

[14]

ι- :. (We) : (z,a). R o z a - ι ζ tut a : & RoZoao

13T

23*

-. ζ tut a

346

Hans-Ulrich Hoche

Dass es sich hier um eine pragmatische Ableitung handelt, ersieht man aus der Verwendung der pragmatischen Regel RP für den Übergang von Zeile [3] zu Zeile [4]. Aus metalogischen Gründen lässt sich natürlich auch hier nicht beweisen, dass wir auf diese Regel unmöglich verzichten können.54 Doch bis zu einem eventuellen Beweis des Gegenteils, nämlich der Konstruktion einer rein logischen Ableitung von [14] aus [1], werde ich davon ausgehen, dass auf der Basis der bisherigen Paraphrase (18') ein formaler Berechtigungssatz aus einem formalen Verpflichtungssatz nicht logisch, sondern nur pragmatisch ableitbar wäre, was gegen unser drittes Adäquatheitskriterium „Was geboten ist, ist auch erlaubt." verstieße.

V I I I . Korrektur und Beschränkung der Verpflichtungssatz-Paraphrase 1. Unter dieser Annahme möchte ich nun fragen, wie man Zeile [1] minimalisti sc h - also mit den geringstmöglichen Eingriffen oder so schonend wie möglich - abwandeln muss, damit sich die vorstehende Ableitung aus einer pragmatischen in eine logische verwandelt. Ein erster Schritt muss offensichtlich darin bestehen, die doxastisch formulierte Zeile [4] schon in Zeile [1] einzuschleusen. Die diesem Ziel dienende Veränderung haben wir natürlich gleichermaßen in dem universellen Wollensgrundsatz wie auch in der singulären Randbedingung der Verpflichtungssatz-Paraphrase (18') vorzunehmen; denn täten wir das nicht, so würden wir die Übereinstimmung unserer neu zu konstruierenden Paraphrase mit den beiden ersten Adäquatheitskriterien - denen der Universaiisierbarkeit und der Präskriptivität - aufs Spiel setzen. Unsere im Hinblick auf das dritte Adäquatheitskriterium so schonend wie möglich veränderte Paraphrase scheint daher zunächst die folgende Gestalt annehmen zu müssen: (18*)

(We) : (z,a). (Bz) R0za

ζ tut a : & (Bz 0 ) RoZ()a0.

Dass diese Paraphrase den beiden erstgenannten Adäquatheitskriterien noch immer genügt, erkennt man durch die Überlegung, dass man den sowohl im Wollensprinzip wie in der Randbedingung enthaltenen Prädikator „(B£) R^Ca" definitori sch durch den Prädikator „R|£a" ersetzen könnte, 55 der sich von dem in der Paraphrase (18') verwendeten Prädikator „R^Ca" lediglich durch den Index unterscheidet, der auf syntaktische Ableitungen aber offensichtlich keinerlei Einfluss hat. 56 « Siehe o. V.2 mit Fn. 49. 55 Vgl. zu einem solchen - auf Frege zurück gehenden Verfahren - Hoche 1992a: 216 f. mit Anm. 296, sowie u. XVII. 1 mit Fn. 88. 56 Freilich könnte man hier einen ungünstigen Einfluss des offen ausgeschriebenen oder durch den abkürzenden Prädikator „RiCa" kaschierten Glaubensoperators „(BQ" befürchten. Die Problematik des seit Quine (etwa 1960: §§ 30 f., 35) so genannten ,Hineinquantifizierens* in nicht-extensionale (,opake4) Kontexte dürfte hier zwar nicht virulent werden, da in Satz (18*) und allen Sätzen, die auf ihn zurück gehen. Variable nicht durch Existenz-, sondern nur durch All-Quantoren über subjektiv-personale Operatoren hinweg gebunden sind

Eine wollenslogische Weiterentwicklung des Universellen Präskriptivismus

347

2. Noch nicht dagegen genügt die Paraphrase (18*) unserem dritten Kriterium; denn der in Zeile [4] unserer letzten Ableitung stehende Ausdruck „(Be) RoZoao" kommt in (18*) j a noch gar nicht vor. U m eine rein logische Ableitung zu gewährleisten, ist es also weiterhin nötig, in der neu zu konstruierenden Paraphrase für die Personenkonstante „z (α) :. (3y)R,yea (We) : (ζ,a). (3y)R,yza ζ tut a : & (3y)R!yea.

Wie man sieht, unterscheiden sich (SGR') und (UGR 44 ) nur hinsichtlich ihrer Vordersätze (58')

(We) : (z,a). R,eza -> ζ tut a

und (594)

(We) : (z,a). (3y)R,yza

ζ tut a.

Diese beiden Sätze stehen zueinander aber insofern in einer bemerkenswerten logischen Beziehung, als sich (58 4 ) aus (59') wollenslogisch ableiten lässt. Von dieser Tatsache kann man sich am einfachsten dadurch überzeugen, dass man den Wollensoperator „(We)" zunächst einmal weglässt und eine rein quantorenlogische Ableitung durchführt: {I )

[1]

(z,a). (3y)R,yza —• ζ tut a

dl

[2]

(3y)RiyZoao

(3)

[3]

R,ezoao

(3)

[4]

(3y)R,yzca0

3 PA

(1,3)

[5]

Zotutao

2,4T

(I)

[6]

RieZoao-»Z(, tuta