By Kevin E. Noonan --
Think tanks, consortia, foundations, subcommittees, and "working groups" frequently assay an area with some social, economic, or technological significance to determine whether issues exist or can be anticipated that deserve to be studied to minimize harm or maximize opportunity. These groups can be helpful in focusing attention of what may be "over the horizon," although it is hard to remember any examples of a report from such groups that actually helped avoid the unforeseen problem. What must be remembered in reviewing the recommendations of such groups (or government agencies like the Federal Trade Commission) is the political aspect: none of these reports ever concludes that "everything is fine, there is nothing to worry about." Dr. Pangloss cannot be found in the roster of luminaries populating such bodies.
All this comes to mind when assessing the recommendations of The Hinxton Group on stem cell policy. The Group's Report, entitled "Statement on Policies and Practices Governing Data and Materials Sharing and Intellectual Property in Stem Cell Science," which issued in February, contains several fairly commonsensical recommendations; that some of them are accompanied by admonitions that they should be adopted through coercion merely reflects the tendency for intelligent and well-minded people not to understand and to be offended by anyone who disagrees with them. More troubling than the recommendations are the justifications for them contained in the preamble of the Report, about which it can only kindly be said suffers from the rhetorical error of assuming the conclusion of the argument it tries to raise.
But first to the recommendations, which number five:
1a: Establish a central hub for accessing global stem cell registry information
The basis for this recommendation is purportedly a lack of data sharing due to a failure to publish or otherwise disclose. The proposed solution is to provide an "information portal" to be established as a resource, taking as examples existing resources such as the National Institutes of Health, the EU and International Stem Cell Registries, to be modeled after NCBI, GenBank, and EMBL Bank. The Report also recommends that the data to be shared be contained in multiple sites (as is genetic information), which is advocated to distribute "funding, physical security, transparent operation and collective ownership."
The Report cites as advantages of such repositories collaboration, incentives for participation, and open access, as well as promoting cooperation and coordination across organizations, standardized formats, information about cells, mutations, characteristic features, publication details, and other aspects of information distribution. It also recommends that participation be coerced, for example by requiring participation as a condition for obtaining grants or access to publication in major journals (or alternatively that participation be left voluntary). It seems that the recommendation that such behavior be compelled rather than voluntary could undermine the purported advantages of this recommendation, by reducing the incentives for disclosure and making more attractive private rather than public funding sources.
1b: Establish a central hub for accessing information about stem cell patents
The Report cites "scholars" as contending that: 1) public databases of patent information "are often difficult to search"; 2) outcomes of patent examination differ in different jurisdictions (which is certainly true); 3) intellectual property rights (IPR) are "copious and atomized into a profusion of patents with overlapping claims"; and 4) "no one is curating the global body of patent data." This results in "considerable uncertainty and enormous costs" in trying to survey the IPR landscape. Evocatively, the Report states that "[e]veryone suffers when there is no map for a new research area, and individual explorers are in no position to do the mapping and have no incentive to satisfy the needs of other stakeholders."
Distinct from the stem cell hub proposed in Recommendation 1a, this recommendation envisions an "information resource" for IPR (called the IPR Resource), and suggests primary (patent) and secondary (scientific journals, etc.) databases and linkages between them. Underlying this proposal is the benefits of coordination and cooperation, including information on patent licensing and assignment information from public sources (such as the trade press) and even a stem cell patent "wiki." While this recommendation undoubtedly could help academic and legal research and researchers, it is unlikely that anyone seeking this information for commercial purposes would neglect to consult a patent attorney, for whom many of these impediments would not be as daunting.
Recommendation 2: Encourage, support and coordinate international human stem cell banks and human tissue and cell repositories
This recommendation is aimed at material transfer agreements and "impediments" to stem cell "sharing" between laboratories (presumably, academic laboratories). Also addressed is the possibility that "[w]e may need new, internationally coordinated mechanisms to deal with emerging issues related to informed consent and privacy." The Report recommends that existing stem cell banks (e.g., UK Stem Cell Bank) be "supported" and that existing stem cell banks and repositories coordinate with one another regarding "standards," proposing "a well‐networked international set of cell banks and repositories could quickly and efficiently distribute existing and newly generated human stem cell lines of common interest."
The Report also advocates that provenance information be coordinated between banks (which, while admirable and useful may conflict with "standards" for protecting privacy), and addresses emerging areas like induced pluripotent stem cell (iPSC) characterization, and standards for inclusion based on academic "popularity," potential for use in "particular therapeutic efforts" and the "level of constraint" there may be on the use of certain stem cells, such as from IPR.
Recommendation 3: Develop and institute incentives for data and materials sharing through publication, participation in information hubs, and other mechanisms
This recommendation is related to the earlier-noted problem of data accession and efficiencies for sharing materials. The Report cites disincentives to "early publication and distribution, especially in industry" and lack of avenues for publishing negative data. The recommendation argues that databases be established, to be populated by the "insist[ance] on the deposition of data, with release on . . . publication." Examples (or perhaps justification) for such restrictions cited in the Report are standards for publishing results of clinical trials from the NIH in collaboration with "the top 20 clinical journals," and microarray standards (MIAME) to which 50 journals ascribe.
The Report also recommends that funding agencies require minimum information on methods etc. regarding a publication, with mechanisms to supplement if information is found to be inadequate. Such efforts should be part of consistent policies between "[r]egulatory bodies, research institutions funding bodies, companies and journals" for data and material sharing, again using a coercive rather than voluntary or cooperative paradigm. The Report also advocates estabilishing bases for promoting release of negative data, for example by entry into a database, and that all publications should conform to guidelines for "appropriate standards for data completeness and norms of behavior."
Recommendation 4: Explore options for formal collaborative networks, patent brokering, and formation of patent pools when those mechanisms for collective management of intellectual property can move the field forward
Turning again to IPR, the Report advances the idea that there is "[c]opious IP" that requires "[c]ollective action . . . to reduce transaction costs and bureaucratic friction that can intrude on market mechanisms to advance stem cell R&D." The Report claims that individual research institutions are "hedging their bets" and "seeking patent rights as a matter of course, in the unlikely event that one of these patents will result in a large financial payoff." This "creat[es] a culture of pervasive patent infringement married to a potential option for prosecuting selected infringement later," creating a "broad shadow of uncertainty about freedom to do research and pursue applications."
This portion of the recommendations highlights a pervasive concern among academic researchers: the unlikely event that mere scientific research will incur patent infringement liability. This fear informs the Report's assertions that IPR promotes "under-investment in new firms, high barriers to entry for new innovators, and slower progress in the field" than would be the case "if individual research institutions were more constrained and targeting in their seeking of patent rights." The "problem" posits a fear of later patent lawsuits from "research institutions with public missions." Of course, the other way to view the current situation is that without IPR, universities would see their publicly funded research pirated by corporations, foreign and domestic.
The Report recommends that the law recognize distinctions between stem cell IPR and other technologies, without any express statement of what those distinctions are. For example:
Intellectual property relevant to stem cell research has several features in common with other technologies, but some features that are distinctive. Many patents have been granted in different countries and multinational patent jurisdictions (such as the European Patent Office). The accumulation of IPR is common for an emerging technology, and since 1998, this has been occurring in human pluripotent stem cell research and its applications.
The Report asserts (without reciting evidence in support of its assertions) that the number and frequency with which researchers are encountering "delays and blockages" may be sufficient to produce a consensus that there is an IPR problem that needs to be addressed, particularly with regard to iPSCs. "The time may be ripe for collective action to ensure that R&D proceeds apace, and with less congestion or friction than is likely to be possible without such coordinated action," according to the Report's authors. Proposals for "disposing of the accumulated IPR in a way that benefits all parties" include:
Patent Pools. Formal patent pools are one possible solution to reducing transaction costs around particular applications or standards (this may include iPSCs). Patent pools require a collection of issued patents that patent holders agree to "pool," meaning that they have a formal contractual agreement to not enforce the patents against one another or against others licensed by the pool. A pool requires valid patents, a gatekeeping function to determine what belongs or does not belong in the pool, a way to value and return revenues for patents in the pool, and sufficient common interests among the patent‐holders to be sustained.
Usenow paylater semicommons. Another model for collective management of IPR involves a set of rules designed and enforced by stakeholders, through a network of agreements. Some agreements may be informal, but a subset of rules and practices needs to be written and formal. The formation of norms and practices around IPR is easier when there is a small number of research funders, but in stem cell research, the emergence of the field from small companies, individual universities and funding by state governments within the US, and many regional and national governments internationally, but without a dominant funding organization, has led to an unusually intense problem of research coordination, coupled to a profusion of IPR held by disparate actors with divergent interests. The development of a semicommons may be a way to address this.
Patent brokers. Short of a formal patent pool, if patent‐holders have generally similar licensing strategies, collections of patents managed by a neutral arbiter could emerge. A "patent supermarket" does not require a strong gatekeeper to vet the patents entering a formal pool, but only a broker to collect patents available to potential licensees to be made available on standard terms. A "royalty clearinghouse" can consolidate and simplify the transactions of incremental royalty payments for such standard term licenses.
Collaborative networks. One promising strategy is to reduce transaction costs by eliminating patents that are never enforced, licensing existing patents on nonexclusive terms except when exclusivity is needed to induce investment in product development, and generally clearing out the accumulated underbrush of IPR detritus. These actions require changes in policy among individual stakeholders in the field, and are likely to emerge only if there are explicit norms articulated by those engaged in stem cell research.
The deficiencies in these specific recommendations is that there is little evidence in the Report to support imposing any of these "controls" on how the various stakeholders are managing their IPR, or that such arrangements are impossible without being imposed by government, funding agencies or other outside forces (in contrast to the experience of the computer industry, for example, where standards-setting and cooperative patent licensing has evolved without such externally imposed conditions).
Recommendation 5: Adopt licensing practices and patent policies that promote fair, reasonable, and nondiscriminatory (equitable) access to knowledge and health care applications
The Report proposes that licensing "should reflect the goal of global justice, borne out of a human dignity common to all and a universal commitment to reduce suffering"; while a laudatory statement of moral behavior, licensing as it is understood in the marketplace is not a flexible means for promoting social goals. These statements are reminiscent of the idea that "a patent is affected with a public interest," and here the interest relates to using the "power of the state" to enforce IPR, which must be done with an "awareness of its social context and utility," requiring "reasonable limits on its use in the form of obligations towards others." The Report also cites as justification the altruism of donors (which is both an assumption and certainly not always a factor in making such a donation, any more that altruism explains all blood donations) and "commitments made to ethics review bodies."
This portion of the Report contains specific recommendations, in contrast to other portions of the Report. Citing to "statements of principle" such as the "Nine Points" adopted by the Association of University Technology Managers (AUTM) and others, they propose:
First, that [a]ny licensing on government‐funded stem cell inventions must:
• Reserve research rights for non‐profit institutions;
• Promote R&D on and access to technologies that can help meet critical health needs in both developing and developed nations. This can be facilitated through the use of, wherever possible, negotiated global access terms and jurisdictional and field‐of‐use limitations;
• Use non‐exclusive licensing of platform technologies and technologies of broad ancillary utility that are instrumental to the development of the field; and,
• Ensure that data and materials are available to government and academic researchers with a minimum of delay.
Second, that "[t]echnology transfer offices in government‐funded research institutions should make public their stem cell IPR, including their geographic scope and licensing history (including where rights have been reserved or non‐assert clauses have been used), in order to promote transparency and greater use of stem cell technologies.
Third, "[p]atent offices and key policymakers should reassess whether the current standards for granting stem cell patents are appropriate, given both the power of broad platform patents to block R&D, and the proliferation of patents that can create uncertainty and fragmentation in the patent landscape.
While reasonable people may differ regarding specific recommendations and the need for the recommendations in the Report in general, in some ways the most interesting aspect of the Report is the Preamble. This section contains the general justification for the recommendations and definition of the problem. Unfortunately, this is also the section that contains the least evidentiary support, and indeed has a tone and tenor that the problems are self-evident. For example:
Tension is increasing between fairly new and pervasive policies and practices governing data and materials sharing and intellectual property in science ('proprietary structures'), and norms of openness and free exchange. While intellectual property rights (IPR) can bring private investment into areas underfunded by governments and help bridge gaps between scientific invention or discovery and useful technologies, some new and emerging policies and practices risk slowing innovation in research and development (R&D) and skewing attention toward large markets, to the disadvantage of small markets, such as those for rare diseases and in some emerging economies. This is of concern, as one central goal of the life sciences is to improve global health: our shared humanity and the potential for biological knowledge to benefit all people create this obligation. Further, the self‐ regulatory structures within scientific communities, as much as the legal institutions we consciously erect for science, should be responsive to this goal.
While the proprietary dilemmas currently faced in stem cell science confound many if not all areas of cutting edge life science, they are especially pronounced in the field of stem cell research. First, the tree‐like shape of cellular differentiation makes the field especially prone to IPR holdings that can function as tollbooths to broad areas of work, creating a drag on investment and slowing down basic research. Second, the consequences of such slowing are especially severe in the stem cell field, where novel cell lines, reagents and related technologies function as platforms for broad areas of follow‐on work. Third, the competition to stake out aggressive patent positions is accentuated in the current context of competitive national innovation policies featuring stem cell science.
None of these assertions is supported by evidence, and in fact there is significant evidence to the contrary. Examples include the expiry of foundational stem cell patents, which will occur within the next 7-10 years; patent challenges to such patents in the U.S. and abroad; and the likelihood that successful commercialization of stem cell science will take much longer than the term of even the most recent patents, and that the growing body of expired patent disclosure will promote the same goals the Report now advocates. The difference, of course, is patent rights prior to expiry will foster investment when it is most critical, at the beginning of the development cycle, nurturing translation of basic research to useful medical technologies. Openness is in fact promoted by the patent system, which requires not only a written description and enabling disclosure but also (at least for now) disclosure of the best mode for practicing the invention. None of these requirements exist with regard to scientific journal articles or public grant proposals, and indeed there are significant incentives against such full disclosure in those documents. While the potential for harm recited in the Report may in fact exist, neither the preamble nor the body of the recommendations establish (or even provide evidence for) the assertion that the Report's recommendations be adopted to avoid such harm, or that the consequences of adopting the Report's recommendations would not cause other, different harms. One of those possible harms is likely to be reducing or limiting full, frank and enabling disclosure of stem cell technology as it develops over the next decades. Such a cure would be worse that the disease.
The Hinxton Group consists of:
Steering Committee:
Sarah Chan, BSc(Hons), LLB, MA (Health Care Ethics and Law)
Deputy Director & Research Fellow in Bioethics and Law
Institute for Science, Ethics and Innovation
School of Law, University of Manchester
Peter J Donovan, PhD
Professor, Departments of Biological Chemistry and Developmental & Cell Biology
Co‐Director, Sue & Bill Gross Stem Cell Center
University of California – Irvine
Ruth Faden, PhD, MPH
Philip Franklin Wagley Professor of Biomedical Ethics
Executive Director, Johns Hopkins Berman Institute of Bioethics
Professor, Department of Health Policy & Management, School of Public Health
Professor, Department of Medicine
The Johns Hopkins University
John Harris, FMedSci, BA, DPhil
Lord Alliance Professor of Bioethics Director, Institute for Science, Ethics and Innovation
School of Law
University of Manchester
Robin LovellBadge, PhD, FMedSci, FRS
Head, Division of Developmental Genetics,
MRC National Institute for Medical Research
Division of Developmental Genetics
MRC National Institute for Medical Research
Debra JH Mathews, PhD, MA
Assistant Director for Science Programs,
Johns Hopkins Berman Institute of Bioethics
Assistant Professor, Department of Pediatrics
The Johns Hopkins University
Alan Regenberg, MBe
Bioethics Research Manager, Johns Hopkins
Berman Institute of Bioethics
The Johns Hopkins University
Julian Savulescu, BMedSci, MB, BS, MA, PhD
Uehiro Chair in Practical Ethics
Director, Oxford Uehiro Centre for Practical Ethics
University of Oxford
David Winickoff, JD
Co‐Director, Science, Technology, and Society Center, University of California – Berkeley
Associate Professor of Bioethics and Society University of California – Berkeley
Executive Committee:
Robert CookDeegan, MD
Director, IGSP Center for Genome Ethics, Law & Policy
Duke University
Gregory Graff, PhD
Assistant Professor, Department of Agricultural and Resource Economics
Colorado State University
Aurora Plomer, BA, MA, LLB, PhD
Chair in Law and Bioethics, Director of SIBLE, School of Law, University of Sheffield
Director, Sheffield Institute of Biotechnology Law and Ethics
University of Sheffield
Kris Saha, PhD
Postdoctoral Fellow, Whitehead Institute for Biomedical Research, MIT
Science Technology and Society Fellow, Kennedy School of Government
Harvard University
Christopher Scott
Director, Program on Stem Cells in Society, Center for Biomedical Ethics, Stanford University
President/CEO, The Stem Cell Advisors
John Sulston, PhD
Chair, Institute of Science, Ethics, and Innovation
University of Manchester School of Law
University of Manchester
Patrick Taylor, JD
Fellow, Petrie‐Flom Center for Health Law Policy, Biotechnology and Bioethics, Harvard Law School
Assistant Clinical Professor, Harvard Medical School
Staff Scientist, Children’s Hospital, Boston, MA
Hinxton Group Members:
Elona Baum, JD (Observer*)
General Counsel, California Institute of Regenerative Medicine
Laura Biron, PhD
Greenwall Fellow in Bioethics and Health Policy, Johns Hopkins Berman Institute of Bioethics, The Johns Hopkins University
Tania Bubela, PhD
Assistant Professor, School of Public Health, University of Alberta, Canada
Francesca Cesari, PhD (Observer*)
Senior Editor, Nature
Haidan Chen, PhD
Post Doctoral Research Fellow, Center for STS, Zhejiang University, China
Jorge Contreras, JD
Director, Intellectual Property Program, School of Law
Washington University in St. Louis
Ishan Dasgupta
Research Program Coordinator, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University
Matthew DeCamp, MD, PhD
Greenwall Fellow in Bioethics and Health Policy, Johns Hopkins Berman Institute of Bioethics, Fellow in General Internal Medicine
The Johns Hopkins University
Richard Gold, SJD
Professor, McGill University Faculty of Law
President, Innovation Partnership
Søren Holm, BA, MA, MD, PhD, DrMedSci
Chair, Center for Social Ethics and Policy, University of Manchester
Professor of Medical Ethics, University of Oslo
Jim Houlihan, PhD (Observer*)
Head of Innovation Policy
UK Intellectual Property Office
Ryuichi Ida, LLB, LLM
Professor of International Law, Kyoto University Graduate School of Law
Member, Expert Panel on Bioethics, Council for Science and Technology Policy,
Japan Member, Bioethics & Biosafety Committee, Ministry of Education, Culture, Sport, Science & Technology, Japan
Kazuto Kato, PhD
Associate Professor of Science Communication and Bioethics, Institute of Research in Humanities, Graduate School of Biostudies
Kyoto University
Annabelle Lever, PhD
Wellcome Interdisciplinary Research Fellow, Institute of Science, Ethics, and Innovation
University of Manchester
Jacob Leveridge (Observer*)
Biomedical Ethics & Medical Humanities Adviser
Wellcome Trust
Reinhard Merkel, Prof, Dr
Institut für Kriminalwissenschaften
Universität Hamburg
Dianne Nicol, LLM, PhD
Professor
University of Tasmania, Australia
Amanda OdellWest, PhD
Lecturer in Law, School of Law
University of Manchester
Beverly A Purnell, PhD
Senior Editor, Science Magazine
Mahendra Rao, MD, PhD
Vice President, Stem Cells at Invitrogen
Adjunct Professor, Buck Institute of Age Research
Vice President, Medicine at Life Technologies
Brock Reeve, MPhil, MBA
Executive Director, Harvard Stem Cell Institute
Harvard University
Mark Rohrbaugh, PhD, JD (Observer*)
Director, Office of Technology Transfer
National Institutes of Health
Mark Sheehan, PhD, MA
BRC Ethics Fellow, The Ethox Centre
James Martin Research Fellow in the Program on the Ethics of the New Biosciences
Oxford University
Glyn Stacey, PhD
Head of Division of Cell Biology and Imaging, National Institute for Biological Standards and Control, Director, The UK Stem Cell Bank
Jeremy Sugarman, MD, MPH, MA
Harvey M Meyerhoff Professor of Bioethics and Medicine
Deputy Director for Medicine, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University
Dieter Treichel, PhD
Patent and Start‐up Manager
Max Planck Innovation
Fanyi Zeng, MD, PhD
Professor, Associate Director, Shanghai Institute of Medical Genetics, Shanghai Stem Cell Institute, Shanghai Jiao Tong University, China
