A Policy Proposal for the Management of Data, Intellectual Property, and Ethics [Full Text Available Here]
Krishanu Saha1*, David E. Winickoff2*, and Gregory D. Graff3*
1 Whitehead Institute for Biomedical Research, Cambridge, MA 02142 2 Department of Environmental Science, Policy, & Management, Univ. of California, Berkeley, Berkeley, CA 94720 3 Department of Agricultural and Resource Economics, Colorado State Univ., Fort Collins, CO 80523 *Authors contributed equally to this work.
ABSTRACT
The need to strike a better balance between free sharing and proprietary and regulatory restraint in the life sciences is becoming an important policy concern in the fields of health policy, law, and bioethics. Here we explore these issues in the field of stem cell research. Expanded funding for stem cell research and development holds unique promise for advancing medicine and human welfare. However, technical, proprietary, and regulatory conditions are not ideal: closed information, congested intellectual property, and regulatory complexity are likely to slow innovation, skew attention towards large markets, and prevent ethical settlement. Accordingly, we propose a new form of collective action among funding agencies, scientific journals, and research institutions to centralize data, cell lines, and technologies and to design and disseminate research tools. The goal is more efficient technology exchange within the research community, orientation of product development towards pressing public health needs, and promotion of ‘best ethics’ in research and development.
THREE PERVASIVE PROBLEMS IN STEM CELL R&D
Within each of three policy domains current conditions present serious problems for the pace of innovation, the distribution of resulting health benefits, and the public accountability of stem cell research. Moreover, these problems interact and are mutually compounding across domains.
Exchange of Data and Materials
Enhanced capacities to produce, manage, and disseminate data through new information technologies have fueled debates about the manner and timing of data release in the sciences [1]. Traditional norms around sharing research inputs have run headlong into the desire of scientists and their institutions to protect their interests in potentially valuable data, materials, and research results. Practices of delay and secrecy have resulted from the increased relevance of university life sciences to commercial markets and private investors [2, 3]. One mark of change is the proliferation of material transfer agreements between universities [2, 4]. Recent studies suggest that data withholding is becoming common and problematic [5].
Intellectual Property Rights
Following patenting trends elsewhere in the life sciences, scientists and their institutions have been claiming the essential building blocks of stem cell research as private assets. In the specific case of stem cell lines, the first and most obvious problem concerning materials arose from the combination of the Bush Administration’s restrictive funding policies and the commanding patent position of the Wisconsin Alumni Research Foundation [6, 7]. Recent analyses show a significant rate of accumulation of new patents over stem cell technologies [8- 11], with problematic implications for downstream innovation [12-14].
Bioethics and Regulations
As if technical and proprietary complexities were not enough, disagreement over ethics has given rise to two major problems for efficient and accountable governance of this work. First, in the U.S. federal moratorium on new human embryonic stem cell (hESC) lines has resulted in a vacuum both of funding and oversight. Even as private and state-funded research moves ahead, a national framework is lacking apart from some 2005 guidelines from the National Academy of Sciences. Second, the resulting state programs have proliferated a patchwork of state regulations that differ, sometimes only slightly, on a range of issues. To amplify matters, similar differences occur globally across national regulatory regimes.
TOWARDS AN INTEGRATIVE APPROACH
Scientists and policymakers have, of course, identified each of these issues, and important initiatives in stem cell research have been undertaken. These efforts should be applauded, but, across the board, they remain inadequate on two counts. First, none of them goes far enough to solve the particular problem it targets. Second, by targeting technical, IP, or regulatory problems in isolation these efforts neglect the important interconnections between these domains. Overlooking interaction between the different domains involves both a conceptual and a practical error. The conceptual error is to ignore the profound ways in which these domains are mutually constitutive categories. Norms and practices of sharing data and materials are simultaneously issues of property and of ethics. Questions of sharing data and materials raise important questions of property which, in turn, raise questions of ethics. To separate these questions is to perform a conceptual purification that, at a minimum, prevents optimal solutions. Yet, the overlap is not merely conceptual, it is practical. As the recently encountered problems with some of the NIH hESC lines illustrate, ethical accountability can be promoted only to the extent that provenance characteristics and data about cell lines are well known and shared [15, 16]. Efficient progress of ethically accountable stem cell research requires considerations that span the complexities and bottlenecks across all three domains. Not only would an integrative approach be more efficient, given the interdependencies, an integrative approach may be the only way to solve some of the individual problems.
THE LOGIC OF COLLECTIVE ACTION
The problems discussed above have not been adequately addressed largely because they are classic collective action problems, in which a diverse set of actors share common interests yet no one individual actor’s incentives are sufficient to overcome the inertia of inaction. Mobilization requires leadership in the form of coordination and initial investment. Sufficient conditions for collective action have not quite yet emerged in any one of the three domains, let alone across them. And, given the currently decentralized pattern of funding and regulation in the U.S.—despite the articulation of clear interests among many parties—there is no clear leader. Under these circumstances, it is necessary to motivate many, heterogeneous potential actors through the use of various carrots and sticks. We argue that collective action with a push from major funding agencies can be a basis for opening up stem cell research in the face of multiple compounding constraints. It is precisely the major funding agencies, such as CIRM or the NIH, that have important roles to play in supporting and enhancing common-access resources in stem cell research. Such an “opening up” would result in a more efficient exchange of data, and with further action, sufficient access to research tools within the stem cell research community. We propose four specific actions for stem cell policy:
1. Lead the development of practical common norms
First, major funding agencies could convene interested segments of the research community to construct a practical normative framework for how stem cell materials and data should be managed and circulated within the community. Participation in the efforts above indicate that this group is heterogeneous and large—including scientists, lawyers, ethicists, state funding agencies, nonprofit agencies, universities, and industry. Leadership from major funding agencies is needed to structure this discussion in finding common ground. This commonly developed normative framework should seek to redress the negative effects spanning the technical, proprietary, and ethical domains.
2. Require access in research contracts
Second, major funding agencies should use funding contracts to require the sharing of research data and materials. By many estimates, stem cell lines and the fundamental protocols of cellular reprogramming and differentiation constitute common resources for the research community that are expected to drive broad progress in biomedical research. Thus, cell lines contain the hallmarks of what have previously been called “community resource projects” [17, 18]. Accordingly major funding agencies could classify the development of new human stem cell lines as a “community resource project”. A key consequence of invoking this norm would be to include sharp stipulations in research contracts concerning access to stem cell lines and their associated technologies. The stipulations need not use a simple “open access” model, but could be structured in a variety of creative ways that would increase their flow while respecting the private rights and claims of inventors and their institutions [19].
3. Build a common data resource
Third, major funding agencies should support a common data resource that encompasses all of the necessary technical, IP, and ethics information that will be used by its funded scientists, and hopefully, by the community of stem cell scientists globally. The lack of success in this area to date suggests that generating and sustaining support and interest for such an initiative will require new carrots and sticks, and complementary efforts among major funders.
4. Foster further collection action
Fourth, major funding agencies should support further efforts to coordinate, design, build, and disseminate research tools and platform technologies to alleviate the most important technical, IP, and ethical bottlenecks facing the field. These first three actions can construct the foundation for further collective action in which research institutions themselves, and not the government, could to take the lead. With sufficient data available, consortia of interested research institutions could perform systematic analyses of key stem cell lines, research tools, or other platform technologies where some combination of technical, proprietary, and ethical bottlenecks have stymied work at the participating institutions and/or their commercial partners. Analysis of particular constraints for a particular cell line, research tool, or other platform technology is a time-intensive task that, if centralized and done once for many, would have significant efficiency gains for scientists, technology transfer offices, and ethics review boards alike. Informed by the results of those common analyses the consortia could go so far as to designing new technologies that work around the most important technical, IP, or ethical bottlenecks. These new technologies could then be developed and made available for both research use and commercial development of downstream applications through collective licensing or “protected commons” strategies—such as open source or patent pooling. The constituent components would be ethically vetted and chosen to meet regulatory standards across multiple jurisdictions. Such creative initiatives have taken root in the fields of agricultural biotechnology and synthetic biology [19-22], and could prove useful for stem cell research [23].
CONCLUSIONS
The field of stem cell research is full of promise. Yet, those who seek today to realize that promise must wade through a morass of data and material transfer issues, navigate or negotiate numerous intellectual property claims, and stand in peril of violating ethical or formal regulatory requirements. Major funding agencies can and should do more with its leadership than simply fund more research, taking a more active role in expanding the institutional underpinnings of a science commons that is under strain. Such leadership could catalyze fundamental normative and institutional changes that would expedite the exchange of technologies within the research community, orient investments over a wider range of public health needs, and promote a more ethically sound advance of stem cell R&D.
REFERENCES
1. Rai, A.K. and R.S. Eisenberg, Harnessing and Sharing the Benefits of State Sponsored Research. Berkeley Technology Law Journal, 2006. 21: p. 1187-1213.
2. Merrill, S.A. and A.M. Mazza, Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health. 2006: National Academy Press.
3. Merges, R.P., Property Rights Theory and the Commons: the Case of Scientific Research. Social Philosophy and Policy, 1996. 13: p. 145-167.
4. Ku, K. and J. Henderson, The MTA? rip it up and start again? Nature Biotechnology, 2007. 25: p. 721-721.
5. Caulfield, T., et al., Patents, commercialization and the Canadian stem cell research community. Regen Med, 2008. 3(4): p. 483-96.
6. Wadman, M., Licensing fees slow advance of stem cells. Nature, 2005. 435: p. 272-273.
7. Loring, J.F. and C. Campbell, Intellectual Property and Human Embryonic Stem Cell Research. Science, 2006: p. 1716-1717. Saha, Winickoff, and Graff, Opening Up Stem Cell Research
8. Esmond, R.W., R.A. Schwartzman, and T.J. Ebersole, Stem Cells: The Patent Landscape. Intellectual Property & Technology Law Journal, 2006. 18(1): p. 1-4.
9. Glanzel, W., Stem Cells – Analysis of an emerging domain of scientific and technological endeavour. Steunpunt O&O Statistieken, K.U. Leuven, 2004.
10. Campbell, D., M. Noiseux, and G. Cote, Potential for Stem Cells Science and Technology in Canada: Great Promises and Challenges. Science-Metrix report, 2004: p. 63-63.
11. Holden, C., Wisconsin Stem Cell Patents Upheld. Science, 2008. 319(5870): p. 1602b-1603-1602b-1603.
12. Scheinfeld, R.C. and P.H. Bagley, The current state of embryonic stem cell patents. New York Law Journal, 2001. 226.
13. O’Connor, S.M., Intellectual Property Rights and Stem Cell Research: Who Owns the Medical Breakthroughs? New England Law Review, 2005. 39.
14. Simkin, M., How will intellectual property factors affect the commercialization of stem cell therapeutics. 2005: BioEurope.
15. Streiffer, R., Informed Consent and Federal Funding for Stem Cell Research. Hastings Center Report, 2008. May-June 2008: p. 40-47(8)-40-47(8).
16. Baker, M., Consent issues restrict stem-cell use. Nature, 2008. 454(7204): p. 556-556.
17. Wellcome Trust. Sharing data from large-scale biological research projects: a system of tripartite responsibility. Wellcome Trust Meeting Report, January 14-15, 2003, Fort Lauderdale, FL. 2003. Fort Lauderdale, FL.
18. Human Genome Program. Summary of principles agreed at the first international strategy meeting on human genome sequencing. 1996. Bermuda.
19. Winickoff, D.E., K. Saha, and G. Graff, Opening stem cell research and development: A policy proposal for the management of data, intellectual property, and ethics. Yale Journal of Health Policy, Law, and Ethics, 2009. IX(Winter).
20. Atkinson, R.C., et al., Intellectual property rights. Public sector collaboration for agricultural IP management. Science, 2003. 301(5630): p. 174-5.
21. Rai, A. and J. Boyle, Synthetic Biology: Caught between Property Rights, the Public Domain, and the Commons. PLoS Biol, 2007. 5(3): p. e58-e58.
22. Porceddu, M.B.C., et al., Constructive Approaches to Intellectual Property Complexity in Today’s Agricultural Technology World. Plant Mol. Breed, 2007. 5: p. 294-295.
23. Winickoff, D.E., K. Saha, and G. Graff, Opening stem cell research and development: A policy proposal for the management of data, intellectual property, and ethics. Yale Journal of Health Policy, Law, and Ethics, 2008. VIII(Winter).
Proprietary Challenges in Stem Cell Research 