Governance and stem cell research: towards the clinic.

• Author: McDonald, Michael
• Position: Canada

This is one of five background papers commissioned for a stem cell research ethics workshop held in Montreal in February 2007, as part of the Canadian Stem Cell Network (SCN) project Towards the Clinic? Ethical, Legal and Social Issues (ELSI) Relevant to Emerging Stem Cell Therapies. In this paper we focus on ELSI issues that are relevant to the governance of stem cell research as it moves towards clinical applications. We have, by and large, focused our attention on the Canadian context--which is complicated enough in its own right--and not tried to provide a comprehensive or comparative international study.

Our strategy in this paper is to first give an overview of the context of Canadian stem cell research as it moves toward clinical applications. In Part 1, we identify principal agents and stakeholders and then describe their interests, accountability relationships and interactions. In Part 2, we identify ethical, legal and social issues that seem novel or unique to stem cell research. Most of these involve the derivation and use of embryonic stem cells. Part 3 highlights "generic" research ethics issues that we deem most pertinent to stem cell research. Finally, in Part 4, we offer some recommendations, most prominent of which is the need to recognise the special opportunity presented by stem cell research for improving ethical governance of health research more generally.

Before turning to the context of Canadian stem cell research, it is important to say a bit about what we mean by the governance of such research and how we identified ELSI issues. One thing that we do not mean to imply is that there is or ought to be a single means of governance for all stem cell research in Canada. As noted in Part 1 below, there are multiple institutional actors and stakeholders that are involved in the movement of stem cell research from the bench to the bedside. Many of these have their own governance structures, which are intended to achieve often divergent and competitive organisational objectives. (1) Their interrelationships are complex.

We would also note that governance involves the use of various forms of power (legal, bureaucratic, financial, rhetorical, etc.) to bring about results either within an organization or in relation to other organizations. (2) Governance is not only about organizational and inter-organizational lines of authority and accountability; it is also about organizational culture and socialization. Hence, governance involves bottom-up as well as top-down considerations.

Our interest is in governance designed to achieve ethical objectives. In many cases, there is a widespread social agreement on ethical objectives. For example, with regard to the ethical treatment of human subjects in research, there is a general consensus that research subjects are volunteers, not conscripts; research should only be conducted when there is sufficient promise of social benefit, the risks to subjects are reasonable and then only with the subjects' consent (or their duly constituted representatives'). Other ethical values are contested, e.g., whether an embryo is entitled to the same protections as human subjects. We note, however, that even when there is consensus around ethical standards, there may still be significant failures in governance arrangements. One of us has argued that this is the case with human subjects protection, claiming in particular that we lack in Canada a demonstrably effective and appropriately accountable evidence-based system of protection. (3) Some of the most challenging governance issues with respect to novel technologies may well be in the most mundane and familiar areas rather than in their novel aspects. We will also argue that even for issues that seem specific to stem cell research, there are important lessons to be learned from earlier developed areas of research-based clinical practice, in particular gene transfer and solid organ transplantation.

1. Context

   The use of stem cells in biomedical research has been the subject of enormous, and often vociferous, public and policy debate around the world, and Canada has been no exception. The promises and hopes for this field of inquiry are substantial, but so too are the ethical, religious or social concerns and challenges. Many of these challenges relate to the nature and conduct of modern bioscience research.

   As with other areas of applied science and biomedicine, such as genomics or nanotechnology, stem cell research operates as a complex, international field of inquiry in which a diversity of stakeholders is involved in a wide range of basic and applied research, e.g., understanding disease aetiology, drug development, and novel therapeutics. Scientists, clinicians and industry partners are increasingly collaborating with governments and civil society (often represented through advocacy groups or charitable organisations) in the development of and debates about the practice and goals of stem cell research. (4) Bioscientists, and for our purposes all those working on stem cells, do not conduct their research in isolation, free from the economic, social, ethical or political concerns of their colleagues or society at large. (5) Instead, these scientists, clinicians and, indeed, bioethicists are embedded, participating in the shaping of stem cell science, public discourse and policy.

   Such complexity may be increasingly the norm in the biosciences--"big science" is now international, increasingly networked and often political. (6) But just because it is normal does not mean that it is stable or free from ethical concern. It is our contention that the very interconnectedness and complexity of relations between the stakeholders in stem cell research raises challenging socio-ethical issues, e.g., with relation to the sourcing of material, conflicts of interest in university-industry-government partnerships, and the framing of appropriate lines of inquiry. As such, reflection about the ethics and governance of stem cell research also needs to pay attention to the complex context and networks within which stem cell research is conducted.

   1. The Stem Cell Network

      In Canada, as in most other developed countries, the vast majority of stem cell research is happening in university research centres, hospitals and laboratories, although biotechnology and pharmaceutical companies are also becoming active in this field. A focal point for stem cell research in Canada is the Stem Cell Network (SCN), a non-profit corporation that began in 2001 with federal funding from a Networks of Centres of Excellence (NCE) grant. (7) The network's mandate is to facilitate the investigation and development of the therapeutic potential of stem cells to treat incurable diseases. It does so by bringing together researchers at 24 university and hospital research centres, with partners in industry, government and non-governmental organizations (NGOs). The major partners in the SCN can be grouped into roughly five categories: 1) universities and research centres; 2) for-profit corporations; 3) professional and medical groups; 4) government departments, agencies and funding councils; and 5) NGOs, disease and charitable foundations and advocacy groups. The network is thus an organisation that brings together stakeholders interested in basic and applied sciences, commercialization and economic development in order to capitalise on the potential of stem cell research to produce novel medicines and treatments.

      Apart from its core NCE funding ($5 million/year), the SCN obtains the bulk of its support from disease advocacy groups or charitable foundations. Governmental support for the SCN comes largely from federal and provincial agencies or departments involved in economic development. Some of the partners receive funding from Canada's major banks (e.g., Toronto Dominion Bank, Scotiabank, Bank of Montreal, RBC Royal Bank), as well as the private sector, especially pharmaceutical companies. The Heart and Stroke Foundation (HSF) and the Juvenile Diabetes Research Foundation (JDRF) are key funders of stem cell research in Canada and active in lobbying for stem cell research, as are many other not-for-profits and foundations. Through these key stakeholders, the SCN is able to mobilise a diverse set of influential interest groups and is becoming an important actor itself in the organisation and development of stem cell research in Canada. As such, it is also a key locus for the examination of the socio-ethical and governance issues in stem cell research. In Figure 1, we provide a concept map of SCN relationships.

      [FIGURE 1 OMITTED]

      One of the major challenges of such networked and socially embedded science is the management of conflicts of interest and conflicting interests. Conflicts of interest (COI) arise when competing interests unduly influence or bias the judgment of a decision-maker who has a fiduciary responsibility to a third party--for example, when a patient advocacy group lobbies government on behalf of a corporate research sponsor in order to achieve various objectives, including ensuring funding for their group. (8) But while COIs receive much attention, they can often be managed through various mechanisms, such as disclosure to ensure transparency of interests, or the removal of interested parties from the decision making process. (9) Conflicting interests, however, may be more difficult to manage because they do not necessarily involve interests that bias a decision maker, but instead arise with the often legitimate competition between different agendas and interests, e.g., differences between stakeholders involved in basic science, commercialization, economic development or disease treatment.

      Whether we are dealing with conflicts of interest or conflicting interests, a key ethics and governance question is, how or should various and often divergent interests be aligned? While all the stakeholders involved in stem cell research--and more...