The field of human stem cell research is buffeted by the forces of hope and controversy, and the interplay between them has contributed to a highly varied environment for conducting stem cell research. International and regional policies covering this work are complex and in flux. The resulting situations both between and within jurisdictions can be termed a 'patchwork of patchworks'.
Meanwhile, the stem cell field is entering a new era. Emerging techniques such as the production of induced pluripotent stem cells and, potentially, human somatic cell nuclear transfer (SCNT) and interspecies somatic cell nuclear transfer (iSCNT), herald advances in drug development and biological understanding. These approaches, while scientifically promising, also raise new ethical and legal concerns. The US Food and Drug Administration (FDA) recently approved, for the first time, a clinical trial using products of human embryonic stem (ES) cells. The political landscape, notably in the United States, is being transformed: new policies are emerging and funding sources are changing. Furthermore, these developments are occurring in the midst of a global economic crisis which is increasing competition for resources and making efficiency all the more important.
If international collaborators hope to move their research into clinical applications, they must be able to navigate the challenges caused by variations in the stem cell research environment and potential policy conflicts. Identifying and responding to these challenges requires understanding how jurisdictions' policies and practices with regard to stem cell research and its applications vary, as well as understanding the factors influencing this variability and where there is potential for harmonization.
A complex patchwork
Stem cell research is, of course, not the only area of research in which there is jurisdictional variation. Others include genomics and genetically modified organisms. However, due to the intense controversies stem cell research generates, in this instance the patchwork is particularly patchy. It therefore provides an excellent opportunity to explore how variations in research environments affect both the direction and efficiency of research. Indeed, stem cell research can be considered a natural experiment that spans the globe. Understanding it could offer lessons for the wider field of science policy.
Stem cell research can be considered a natural experiment that spans the globe. Understanding it could offer lessons for the wider field of science policy.
Variation in stem cell research environments cannot be reduced to what is and is not permitted by law. Many other elements, from research ethics to social norms, from political history to commercialization capacity, must be considered. First though, we should highlight a few of the key variables that contribute to the overall variation.
Legal regulation of stem cell research varies profoundly. Countries differ over whether human ES cell lines can be imported into or derived within their borders (Table 1). Those that permit the derivation of such lines differ in the sorts of embryos that can be used and how such research is approved. In some cases, there is wide variation within a country. For example, in the United States, state rules differ dramatically regarding the procurement of gametes, embryos and other cells from human donors, the derivation of new Human ES cell lines, and their uses1.
Table 1: A small sample of how regulations governing human ES cell research differ from country to country.
Public perceptions regarding stem cell research also vary widely. This divergence is no surprise given the diverse religious and cultural norms that inform positions on stem cell research globally2. Attitudes toward science and regulatory institutions as well as religiosity, media use, gender and other factors all shape public views3, 4, 5.
In particular, the use of human embryos has been a flashpoint for controversy. A recent comparison of nine European countries found a plurality of perceptions on embryo research, ranging from the view that human embryos have the same status as live human beings (e.g. Austria and Germany), to the view that early-stage human embryos are insufficiently developed to constitute individual human beings (e.g. Denmark and the United Kingdom)6. Although the area has been less studied, public resistance to the use of SCNT appears greater than resistance to human ES cell research, at least in Britain7 and the United States8.
Though public opinion may be broadly suggestive of political directions9 and is, at times, implicated in policy-making discourse10, the role that public opinion actually plays in policy making varies considerably. In some cases, policy makers explicitly use it to inform decisions (e.g. the UK Human Fertilisation and Embryology Authority's public consultation on hybrids and chimaeras11). In other contexts, public opinion seems at odds with policy, as in Canada where there seems to be public support for SCNT, which is in fact prohibited by law10.
Patent policy in the general field of biotechnology is already varied, as are opinions on its role and impact. Countries vary even more widely regarding the areas of stem cell research deemed patentable. In the United States, human embryonic stem cell lines are clearly patentable (e.g. Thomson, J.A. U.S. Patent No. 5,843,780, 1998; Thomson, J.A. U.S. Patent No. 6,200,806, 2001; WARF, 2008). Conversely, the European Patent Office recently refused to grant a patent covering the use of human ES cells, on the grounds of public order and morality12. In other jurisdictions (e.g. Canada) the future of human ES cell research patents is less clear. The impact of patent policies on research is a potentially significant issue that remains uncertain and should be monitored.
How stem cell research is funded and the focus given to commercialization also varies greatly. In some jurisdictions, such as Singapore and California, stem cell research is part of a state-sponsored economic and scientific platform and its funding is part of a specific strategic initiative13. In others, research in the area is primarily supported through government funding, granting agencies and foundations (e.g. the United Kingdom and Canada). In yet others, such as the United States, funding is associated with restrictions limiting the materials or purpose of research.
There are many examples of potential variation besides legal regulation, public perception, policy making, patenting, funding, and commercialization discussed above. Other sorts of variation include the following:
- clinical trial regulations (e.g. use of biologics, privacy rules, informed consent and assessment of risk);
- research ethics norms (e.g. associated with donation of embryos and tissues; often undefined or in flux14, 15);
- standards of research conduct;
- technical research standards (e.g. derivation and maintenance of cell lines);
- jurisdictional research capacity (e.g. ability to conduct clinical trials and industry receptors), and
- health care systems (including issues of access and social justice).
Several projects are underway to harmonize policy, coordinate the ethical review of stem cell lines and materials, and promote the transparency and enforcement of regulations. Important players include the International Society for Stem Cell Research (ISSCR); the Interstate Alliance (in the United States), and the United Nations Educational and Scientific Organization. Nonetheless, much uncertainty and disagreement remains over appropriate conduct both between and within different jurisdictions.
Influence and relevance of the patchwork
How this variability impacts on the stem cell research environment is unclear, although conduct of research, collaboration, efficiency and clinical translation are almost certainly affected. For instance, differing regulations regarding the procurement, derivation, banking, distribution and use of stem cell lines will affect the sharing of materials and data and, ultimately, research productivity. It could inhibit collaboration within and between countries, restrict the flow of research and researchers, and impede clinical translation16. Policy variations on, say, the importation of gametes or other lines also may prohibit some scientists from working on potential collaborators' cell lines17, 18. For example, a line derived through an egg-sharing arrangement in the United Kingdom may not be eligible for study with funding from the California Institute of Regenerative Medicine.
A systematic analysis of the relevant factors, both individually and in combination, is critical for understanding the dynamics shaping the broad research environment. However, because these variables change over time and even vary within jurisdictions, such analysis is difficult, and identifying and measuring the influence of specific factors is particularly so. While this analysis will necessarily be broad and multifaceted, certain questions seem particularly ripe for study:
- How do divergent policy frameworks and governing regulations affect the conduct of stem cell research, including procurement, derivation, banking, distribution and use of stem cell lines?19
- To what extent, if any, do permissive regulatory policies translate to increased productivity? Though early evidence suggests policy variation impacts research outputs20, 21, further study in this area is required.
- How do intellectual property protections (i.e. patents) affect innovation and collaboration? Assessing the stem cell patent patchwork could identify hurdles in different forms of patent landscapes, in order to shape future policy22, 23, 24, 25, 26, 27.
- What potential human and ethical costs are associated with policy patchworks and how can they best be addressed? For example, international stem cell tourism, where patients seek unproven and potentially risky stem cell treatments in countries with lax regulations, is a growing concern28, 29.
- How can the movement of scientists across international borders facilitate the cross-cultural comparison of norms and inform the development of ethics education programs?
The benefits of variability should also be explored. With all the ethical, religious, intellectual, social, and cultural beliefs the world encompasses, some degree of policy variation is healthy and inevitable. Plurality invites innovation, prevents extremism, and allows unlikely but potentially fruitful collaborations. Thus, we should not strive blindly for policy convergence as it is clearly not appropriate in all circumstances.
However, in some contexts uniform policies will be particularly beneficial. For example, research standards, clinical readiness, cell-line quality and scientific integrity are areas where harmonization seems both attainable and desirable. Excellent examples of ongoing efforts to promote international cooperation for research and clinical purposes include the International Stem Cell Banking Initiative (coordinated by the UK Stem Cell Bank), the ISSCR's Registry of Provenance of Human Embryonic Stem Cell Lines and the European Commission's European Human Embryonic Stem Cell Registry16.
To best handle variability, the stem cell community needs to identify how much consistency is necessary for effective cooperation and how best to manage differences. Obviously, identifying clear and transparent policies will facilitate this process and encourage more efficient research. With so much invested in stem cell research, focused consideration on how to enhance this endeavor and promote its progress — particularly towards clinical translation — is merited. If the lessons learned can be applied to the scientific enterprise more generally, so much the better.