Governing controversial science: Lessons from stem cell research

Manuscript prepared for special issue of Policy and Society on the theme of Policy and Genomics.

Abstract

Developments in genomic science and biotechnology are creating new governance challenges concerning funding, oversight, and regulation of the underlying science and its applications. Among forms of genomics and biotechnology, human stem cell research has been one of the most controversial. It holds great promise for the development of medical therapies, but the link between human reproduction and research on embryonic stem cells has fuelled serious opposition. We contend that good policy design can reduce tensions around the advancement of controversial science and technologies flowing from it. This article examines issues in the governance of human stem cell research using evidence from California. Four lessons are drawn for the effective governance of other areas of human genomics and biotechnology. They are (1) isolate structural design from controversy; (2) make room for laypeople in the governance structures; (3) promote transparency, minimize secrecy; and (4) create opportunities for learning and innovation.

Controversy can often stall and frustrate public policymaking. This has led various observers to doubt the ability of public entities to be developed and operated effectively (Bok, 2001; Moe, 1991; Wills, 1999). But thorough debate about issues and reflection on why controversy has arisen can sometimes promote good policy design (Schön & Rein, 1994; Thacher & Rein, 2004). Developments in genomic science and biotechnology are creating new governance challenges for governments operating both at the national and sub-national levels around the world. Questions concerning the funding, oversight, and regulation of the underlying science and its applications are complicated by the use of human tissue in this work, and ethical concerns that arise from that. Among forms of human genomics and biotechnology, human stem cell research has been one of the most controversial (Johnson & Williams, 2005; Magill, 2002). It holds great promise for the development of medical therapies for patients suffering from life-threatening diseases. But the linkage between human reproduction and research on embryonic stem cells has fuelled serious opposition from groups who campaign for the right to life of the human foetus. Significant moral issues have arisen. Beyond this, some scientists, taking a more pure science approach, have argued for their freedom to explore where the science leads them. Meanwhile, from an economic development perspective, funding research involving human stem cells has been seen as an investment that, while risky, could yield huge future gains. All of these issues have raised questions regarding the governance of this controversial science (Mintrom, 2009).

A useful definition of public governance views it as the regime of laws, rules, and administrative practices that constrain, prescribe, and enable the provision of publicly supported goods and services (Heinrich, Hill, & Lynn, 2004). We follow a similar definition here. Using evidence from California, we examine issues in the governance of human stem cell research. We focus on strategies for funding, oversight, and regulation of that research. Relative to other states in the United States, California has done an enormous amount of capacity building in scientific research over many decades. That investment has delivered major pay-offs. For example, California hosts 10 universities ranked among the top 100 in the world in 2007.¹ In addition, relative to other states in the United States, California has consistently been ranked top of the nation in attracting high amounts of research funding per capita from national funding sources, such as the National Science Foundation, the Department of Defense, and the National Institutes of Health.² But California has not been immune to controversy over the scientific work conducted there. Considerable controversy has surrounded the funding of stem cell research in the state. The governance of this research in California encourages public input into shaping the guiding rules for scientists. Controversy and the response of promoting broad participation in decision-making and scientific governance do not appear to have unduly inhibited the research process. Indeed, good grounds exist for arguing that the allocation of funding, oversight processes, and regulation of stem cell research in California are very effective at promoting efficient outcomes, even in the face of complexity and controversy.

The governance of human stem cell research in California offers lessons for other jurisdictions that have been wrestling with the governance of controversial science. To make those lessons explicit in this article, we have followed Richard Rose's prescriptions for lesson-drawing in comparative public policy (Rose, 1993, 2005). That is, we have chosen to focus on a specific governance regime that appears to have been successful at achieving its intended goals. We have then sought to abstract a cause-and-effect model from what we have observed. Finally, we have speculated on the likely consequences of applying the model elsewhere. In so doing, we have been cognizant of the following observation made by Rose: “A lesson is not a photocopy of a foreign program, nor is it a model devoid of national context. A lesson is created by ‘re-contextualizing’ the generic model.” (Rose, 2005, p. 10). Use of this lesson-drawing approach allows us to leverage knowledge from California to inform policy design elsewhere. More specifically, we have drawn four lessons from the California case: (1) isolate structural design from controversy; (2) make room for laypeople in the governance structures; (3) promote transparency, minimize secrecy; and (4) create opportunities for learning and innovation.

We have structured this article in four main parts. First, a brief overview is provided of human genomic science and human stem cell research. An explanation is given here for why a focus on the governance of human stem cell research represents a useful way to explore broader issues in the governance of controversial science. Second, an investigation is presented of the linkages between aspects of governance regimes and scientific outcomes. This part of the discussion provides a justification for the focus on governance of human stem cell research in California. Third, salient aspects are reviewed of the governance, funding, and regulation of human stem cell research in California. Fourth, we present and discuss the lessons we have drawn from the California case with the purpose of informing policy design for the governance of other areas of genomics and biotechnology. The overarching goal of this article is to highlight how good policy design can reduce tensions around the advancement of controversial science and related applications.

1 Genomic science and stem cell research

In almost every cell of every living organism, genetic material exists containing the essential information necessary to guide the organism's development and operation. This genetic material is contained on chromosomes, which are complexes comprising DNA (de-oxyribonucleic acid) and proteins. Every chromosome contains a number of genes, each of which has a specific molecular sequence of DNA that codes information. Each cell (with a few exceptions) contains one set of complete chromosomes. This is called a genome—the set of genetic material for that organism. Although all cells within an organism contain the same genetic information, as they develop they become specialized, which allows them to carry out very different and specific functions throughout the body. The genome interacts with the environment, molecules, other cells, and itself to regulate which proteins are produced, and in what quantities. Each cell uses this genetic information to make a large variety of proteins. These proteins can perform a range of functions, including structural, storage, and hormonal functions.

In contrast to specialized cells, stem cells are uncommitted cells serving no specific purpose. They remain uncommitted until they receive signals to develop into specialized cells. Scientists have speculated about stem cells and their qualities for over a century (Ramalho-Santos & Willenbring, 2007). The existence of stem cells was discovered mainly through investigations into animals, particularly mice. Stem cells are known to exist in both adults and embryos, and stem cell researchers have studied the behaviour of both adult stem cells and embryonic stem cells. However, questions remain concerning the plasticity of non-embryonic stem cells—that is, their ability to transform into a variety of specialized cells (National Institutes of Health, 2006).

In 1981, researchers from Cambridge University in the United Kingdom reported methods for growing mouse embryonic stem cells (Evans & Kaufman, 1981). In 1998, researchers from the University of Wisconsin—Madison reported the isolation of human embryonic stem cells (Thomson et al., 1998). Embryonic stem cells are derived from cells called the inner cell mass, which is part of several-day-old embryos, or blastocysts. If left in the right environment, these cells would develop into an embryo. Once removed from the blastocyst, the cells of the inner cell mass can be cultured into embryonic stem cells. These embryonic stem cells are not themselves embryos and evidence has shown that these cells do not behave in the laboratory as they would in the developing embryo. After researchers have isolated stem cells from a human embryo, the cells can often replicate indefinitely if kept in the correct environment. This creates what is termed a “cell line”.

The ability of the Wisconsin team to isolate human embryonic stem cells and cultivate stem cell lines was a significant scientific breakthrough. Evidence has subsequently emerged that these cells are capable of becoming almost all of the specialized cells of the body and may have the potential to generate replacement cells for a large number of tissues and organs, such as the heart, the pancreas, and the nervous system. Because of this, stem cells are seen as having several important scientific and medical applications. These include being used for repair or replacement of cells or tissues that are damaged or destroyed by a variety of diseases and disabilities, testing new drugs in a controlled and safe setting, and studying genetic function and development processes (National Institutes of Health, 2001).

Genomic science aims to determine the entire DNA sequence of organisms, and then understand the function and interaction of the genes involving fine-scale mapping of individual genes. Developments in genomic science have produced important insights concerning the nature and function of stem cells. Understanding the total genetic component of the stem cells allows investigation into the specific molecular mechanisms of development and specialization. It also advances stem cell research by improving understanding and characterization of the source cells. In turn, stem cell research has contributed much to genomic science, by advancing knowledge of the characterization of genomes and the function and purpose of genes.

Controversy surrounds the study of human embryonic stem cells because their harvest to date has required the destruction of fertilized human eggs. The deliberate creation of a potentially viable human embryo purely for the harvesting of stem cells has been viewed by many as immoral. People taking this position have opposed human embryonic stem cell research because they hold that human life begins as soon as an egg is fertilized, and they consider a human embryo to be a human being. They therefore consider any research that necessitates the destruction of a human embryo to be immoral. Meanwhile, proponents of such research have pointed out that in the natural reproductive process, human eggs are often fertilized but fail to implant in the uterus. A fertilized egg, they argue, while it may have the potential for human life, cannot be considered equivalent to a human being until it has at least been successfully implanted in a woman's uterus (AAAS, 2007).

While some have considered embryonic stem cell research to be justifiable for the advancement of scientific knowledge, they have worried greatly about the future (Fukuyama, 2005). Looking ahead, the possibility arises of extensive growth in markets for the trading of human eggs. This would create incentives for women to produce and sell eggs that would then be fertilized to create embryos solely for the purpose of destroying them at the blastocyst stage to harvest the stem cells. As is, trading of human eggs has become common in response to the demands of infertile couples to gain access to donor eggs for making babies (Withrow, 2007). Scientists seeking to work with human embryos for stem cell research obtain human eggs from in vitro fertilization clinics. In the process of treating infertility, more eggs are produced than are used for the purposes of creating viable embryos. Surplus eggs can be stored, discarded, or donated to research (Trivedi, 2007). Proponents of embryonic stem cell research have held that it is morally permissible to use surplus embryos for potentially life-saving biomedical research. Opponents have objected to this argument, however, saying that such research would still condone the destruction of embryos.

Some stem cell research is non-controversial, such as that performed on cells derived from placentas discarded at birth or tissue from adult skin cells. Indeed, work by James Thomson and his Wisconsin team announced in November 2007 could eventually take much of the heat away from the controversy over embryonic stem cell research. This is because Thomson's team have discovered how to use genetic modification to reprogram non-embryonic human cells so that they exhibit the essential characteristics of embryonic stem cells (Yu et al., 2007). This work holds significant promise because it allows for the possibility of using a patient's own skin cells to create genetically matched stem cells that could be used to make replacement cells and tissues for that patient, without the risk of rejection by the immune system. However, questions remain about the similarities and differences between embryonic stem cells and stem cells derived through genetic modification, making on-going work with human embryonic stem cells crucial to the advancement of this scientific work (Kolata, 2007).

Issues surrounding human cloning also arise in the management of human embryos and the harvesting of embryonic stem cells. That is because the only technique known so far for growing stem cells genetically matched to a subject has involved injecting cells from that subject into a human egg to clone that person and then extract the embryonic stem cells from the blastocyst. Such a procedure and the moral issues associated with it could also be rendered redundant through the research into reprogramming of non-embryonic human cells into stem cells. However, to date, the issue of cloning has created another point of deep controversy, both in the United States and elsewhere (Fukuyama, 2005).

Human stem cell research has been advancing rapidly over the past decade. As it has developed, a range of controversial issues have arisen around management of the science. Given the current state of work on human stem cells, the controversy that has surrounded it, and the public policy challenges that this research has posed for governments both at the national and sub-national levels, many opportunities exist for learning how this science can be effectively governed. Here, we have chosen to focus on the governance of stem cell research as a way of drawing lessons concerning the governance of other controversial science, including human genomics and its applications. Consistent with comments made by other scholars and commentators, William B. Hurlbut has argued that “[t]he current conflict over embryonic stem cell research is just the first in a series of difficult controversies that will require us to define with clarity and precision the moral boundaries we seek to defend” (Hurlbut, 2006, p. 823). We concur with Hurlbut that the controversy over stem cell research has served as a bellwether for future controversies relating to human genomics and its applications. The effective governance of any controversial science calls for careful and coordinated development of funding, oversight, and regulatory regimes. Policy design work prompted by the controversy over stem cell research can hold lessons for governance of other aspects of controversial science.

2 Governance and scientific outcomes

We have presented our rationale for focusing on the governance of stem cell research to draw lessons about the governance of controversial science more generally. We now present our rationale for treating California as an exemplary jurisdiction, from which lesson-drawing for elsewhere makes good sense.

We initiated the case-selection process by asking: where is stem cell research being done? We studied the contents of two top ranked scientific journals, Science and Nature. During the period from January 1998 through December 2008, 64 original research articles published in Science contained the term “stem cell” in either the title or the abstract. We performed a place-of-origin analysis on those articles. Of the 64, the lead authorship for 41.5 (65%) was attributed to scientists based in the United States. The second-most productive country was Japan. In that same period, scientists from Japan served as lead authors on 4.5 (7%) of the articles on stem cells published in Science. Results of an analysis of publications in Nature over the same period were consistent with the results of the Science analysis. During the period from 1998 through 2008, Nature published 134 articles on stem cell research. Of these, the lead authorship of 97 (72%) was attributed to scientists based in the United States. Despite concerns raised during the years when the administration of President George W. Bush placed significant restrictions on the use of human embryos in stem cell research funded by the United States Government, the pre-eminence of the United States as the leader in this research never waned.

Based on the significance of the United States in our place-of-origin analysis of major contributions to stem cell research, we decided to confine our investigation of governance regimes to the United States. The governance of science in the United States is strongly affected by laws and funding processes operating at the state-level. We performed at the state-level in the United States an identical place-of-origin analysis of contributions to Science and Nature. During the period from January 1998 through December 2008, 41.5 original research articles on stem cells published in Science had lead authorship attributed to scientists based in the United States. Of those 41.5 articles, 27.25 (66%) were attributed to scientists located in just four states. Specifically, 9.75 (24%) came out of California, 6.5 (16%) came out of Maryland, 6 (14%) came out of Massachusetts, and 5 (12%) came out of New York. An analysis of publications in Nature over the same period produced consistent findings. From 1998 through 2008, 97 original research articles on stem cells published in Nature had lead authorship attributed to scientists based in the United States. Of those articles, 79 (81%) were attributed to scientists located in the four states noted above. Specifically, 31 (32%) came out of California, 30 (31%) came out of Massachusetts, 12 (12%) came out of New York, and 6 (6%) came out of Maryland. While scientists in 26 states in the United States contributed articles on stem cells to Science and Nature during the period from 1998 through 2008, contributions from California were the most consistently strong.

These results of the place-of-origin analyses of published stem cell research suggested that a focus on California would be appropriate for our investigation of policy design for the governance of controversial science. But further preliminary analysis was performed to explore the differences across jurisdictions in their engagement with stem cell research. This work initiated our consideration of differences in governance arrangements across jurisdictions.

In seeking to account for the concentration of stem cell research in specific places, we hypothesized that the strength of local scientific communities would matter. To test this, we performed difference-of-means tests on the location of universities ranked among the top 100 in the world and the place-of-origin of the stem cell publications in Science from January 1998 through December 2008. Scientists from 13 countries published articles on stem cells in Science during this period. All but one of those countries were members of the OECD.³ Among the 30 OECD member countries, 12 host at least one university ranked in the top 100 in the world in 2007.⁴ The OECD countries produced 63 papers published in Science on stems cells during the period, for an average of about 2 publications per country. However, the average number of publications for the 12 countries hosting one or more top ranked universities was 5. This compares with an average of close to 0 for the 18 countries without a top ranked university (t =1.78, d.f.=1,28, p <0.043, one-tailed test).⁵

We performed a similar analysis for states within the United States. The United States hosts 50 universities that were ranked in the top 100 in the world in 2007. These universities are located within 23 states. Within those 23 states, the distribution of top ranked universities is uneven. California hosts 10, making it the lead state for the concentration of world-ranked universities. (Indeed, if California were an independent country, it would rank third in the world, behind the United States and the United Kingdom, for hosting the largest number of universities in the top 100 in the world.) The states in the United States with the next highest concentrations of top ranked universities are New York (5), Pennsylvania and Texas (4 each) and Illinois and Massachusetts (3 each). The United States produced 41.5 papers published in Science on stems cells from January 1998 to December 2008, for an average of less than one per state. The average number of publications for the 23 states hosting one or more top ranked universities was about 2. This compares with an average of close to 0 for the 27 states without a top ranked university (t =3.53, d.f.=1,48, p <0.001, one-tailed test). These findings reveal the importance of a strong local scientific community in accounting for the concentration of stem cell research.⁶

To further test the argument that the concentration of stem cell research in specific places is dependent upon the strength of local scientific communities, we considered the flow of money from the National Institutes of Health (NIH) in the United States to the individual state-level. We converted the dollar amounts flowing to each state into per capita amounts. In 2008, states received, on average, $59 per capita in NIH research funds.⁷ In the 23 states where scientists published articles on stem cells in Science between January 1998 and December 2008, the average amount of NIH funds received per capita was $89, versus $43 per capita in the 27 states where no scientists published articles on stem cells in Science (n =50, d.f.=1,48, t =3.04, p <0.002, one-tailed test).⁸

An argument could be made for focusing on more than one state in the United States in order to assess approaches to the governance of stem cell science. However, we chose to focus exclusively on California for three reasons. First, California has a very strong science community contributing to this research. Second, scientists in California have exhibited sustained consistency both in the quality and quantity of their contributions to advancing stem cell science (as measured by publications in top science journals). Finally, California was the first state in the United States to move to creating a supportive local environment for stem cell research, following the restrictions on federal research funding announced by President George W. Bush in August 2001. The first move towards creating this environment was initiated in 2002.⁹

3 Governing stem cell research—a focus on California

California's efforts to fund, oversee, and regulate human stem cell research have occurred within the context of actions taken at the national level by the United States Government. Since 1995 – before stem cell research became controversial – the United States Congress banned funding through the National Institutes of Health for any research that would involve creating or destroying human embryos. After the announcement in November 1998 that James Thomson and his team in Wisconsin had isolated human stems cells and created stem cell lines, the question arose as to whether federal funds could be used to support research on human embryonic stem cells.¹⁰ After deliberations that occurred during the end of the presidency of William J. Clinton and the beginning of the presidency of George W. Bush, the National Institutes of Health developed a set of guidelines concerning the funding of human stem cell research.

On August 9, 2001, President Bush made a primetime address to the nation on the topic. To avoid the potential for the federal government to fund the destruction of human embryos in the service of stem cell research, President Bush announced that federal funds would be made available to support research only on stem cell lines derived from human embryos prior to that day, August 9, 2001. He said funding should be permissible for research on these stem cell lines where “the life and death decision has already been made”. President Bush further noted that stem cells can be derived from sources other than embryos and that federal funding would be made available to promote more stem cell research of this kind. President Bush also announced the establishment of President's Council on Bioethics.

After 2001, Democratic Party members of the United States Congress and their moderate Republican Party counterparts made various bi-partisan efforts to expand the set of human embryonic stem cell lines on which research could be conducted with federal funding. Those efforts were prompted by claims from members of the scientific community that the stem cell lines permitted for use under the Bush funding regime were inadequate in number and quality. In July 2006 and again in June 2007, President Bush vetoed bills that would have expanded the set of human embryonic stem cell lines on which research could be conducted with federal funding.

President Bush's address of 9 August 2001 focused exclusively on the issue of federal funding of this controversial science. He placed restrictions only upon federal funding, not upon human embryonic stem cell research itself. Thus, restricted federal funding became available for this research, where no federal funding had been previously available. The establishment of a President's Council on Bioethics suggested the future possibility of national regulations concerning stem cell research. However, while the Council on Bioethics produced a range of background papers on relevant ethical issues, no such regulatory framework was subsequently developed. Taken together, President Bush's clear signalling of the national significance of human stem cell research, his provision for limited federal funding, and the lack of effort to establish national regulation of this controversial science served as an invitation for state-level actions.¹¹

In 2002, California became the first state in the United States to pass legislation that explicitly allowed stem cell research involving both the destruction and donation of human embryos. The bill, sponsored by State Senator Deborah Oritz and co-authored by Assembly Member Howard Wayne (both Democrats) and signed into law by Governor Gray Davis (also a Democrat) was intended to bolster the attractiveness of California as a location for stem cell researchers. No new funding was associated with passage of this law. It required that research involving the derivation and use of human embryonic stem cells, human embryonic germ cells, and human adult stem cells be reviewed by an approved Institutional Review Board. This law also facilitated the voluntary donation of embryos for stem cell research. It required that individuals receiving infertility treatments be provided information regarding the disposal of an embryo, including the possibility of donating embryos for research. It prohibited the sale of embryos.

In 2004, Governor Arnold Schwarzenegger (a Republican) gave his endorsement to Proposition 71, the California Stem Cell Research and Cures Act. The Proposition was designed to amend the state constitution to further facilitate embryonic stem cell research. The proposition also established the California Institute for Regenerative Medicine (CIRM) – the state stem cell agency – and authorized a bond sale to allow around $300 million per year for embryonic stem cell research over a 10-year period. That level of expenditure represented significantly more than what the federal government was committing to stem cell research at the time. The move to secure extensive state support for stem cell research in California was spearheaded by a coalition consisting of venture capitalists, leaders of biotechnology firms, and representatives of the state's strong scientific and medical research communities. They were readily able to make powerful arguments to state political leaders and citizens alike that funding for stem cell research promised major pay-offs for California. These pay-offs were presented as the saving of lives through scientific advancement and the securing of greater economic prosperity through the expansion of high-technology industries.

California's Proposition 71 passed with support from a strong majority of voters. However, opponents of the proposition, led by conservative Christian groups, subsequently initiated a series of law suits that hindered the ability of CIRM to be funded from bond issues. Until 2007, the Institute and its programs were funded through the state budget and private donations. To date, it has established a variety of policy frameworks, research guidelines, and project funding streams. The work of the Institute is guided by the Independent Citizens’ Oversight Committee (ICOC). As of early 2009, the CIRM governing board had approved over 200 research and facility grants totalling more than $614 million. This made CIRM the largest source of funding for human stem cell research in the world.

The law change of 2002, Proposition 71 approved in 2004, and the subsequent development of the state stem cell agency have all been premised on the desire to keep California at the forefront of stem cell research. But these measures have been taken against a backdrop of controversy. Citizen groups in California – especially those organized on the basis of religious affiliation or specific disabilities – have questioned the ethics of this research and the merits of directing funds into scientific work rather the alleviation of suffering using current medical practices (Benjamin, 2008). While it is extremely difficult for those designing governance regimes to meet the criticisms of all interested parties, considerable consultation efforts have occurred in California. These efforts do not appear to have been cynical exercises designed to silence critics.

As efforts have been made in California to promote human stem cell research, public input has been accepted as a procedural step that can improve the quality of the governance regime. This can be seen most clearly in the language of Proposition 71 and in the subsequent operations of the Independent Citizens’ Oversight Committee (ICOC) that governs the California Institute for Regenerative Medicine (CIRM). Robert Klein –who drafted Proposition 71, who thus was the architect of these governance arrangements, and who now chairs the Oversight Committee – has been careful to be respectful of citizen concerns while seeking to create the best possible conditions for researchers. For instance, when asked to explain why he did not make provision for full public disclosure of the financial interests of researchers applying for funding or peer reviewers, Klein stated:

When I wrote the initiative I looked at practices throughout the country – at patient advocacy groups, grant-making organizations and the National Institutes of Health (NIH) – and came to the conclusion that if we are going to attract the best and brightest minds, we have to give them confidentiality for their brilliant new ideas.

Those wanting more financial disclosure fall into two categories: people that legitimately want as much public disclosure as possible and those who are ideologically opposed to the research and make unreasonable demands for public disclosure as a way to undermine the research. This is a dynamic balance and we will provide as much disclosure as possible (Check, 2007).

Next we review the design principles and actual operations of the California Institute for Regenerative Medicine and the Independent Citizens’ Oversight Committee. We explain why the California model represents good governance of controversial science.

3.1 Structure and function of the Independent Citizens’ Oversight Committee

Proposition 71 contained detailed descriptions of the structures to be used to govern stem cell research in California. Those details have subsequently been followed during implementation. The California Institute for Regenerative Medicine (CIRM) is governed by a 29-member Independent Citizens’ Oversight Committee (ICOC). That Committee is comprised of 19 representatives of specified University of California campuses, other public or private California universities, non-profit academic and medical research institutions, companies with expertise in developing medical therapies, and disease research advocacy groups. The Governor and other top-ranking appointed or elected state officials are required to appoint 10 laypeople to serve on the ICOC. Those laypeople represent particular disease advocacy groups, such as advocates for patients with spinal cord injury, Parkinson's disease, or HIV/AIDS. The meetings are governed by California's open meetings act and public records act.

The structure of the ICOC includes three working groups. The Scientific and Medical Research Funding Working Group is responsible for deciding the allocation of funds to researchers. The Scientific and Medical Research Facilities Working Group allocates funding for infrastructure to support stem cell research in California. The Scientific and Medical Research Standards Working Group has established the regulatory framework guiding research funded by the Institute. By designs written into Proposition 71, all of these working groups are composed of several laypersons from the ICOC representing disease advocacy groups augmented by a larger group of individuals with relevant and recognized expertise in the area. The ICOC is required to take advice from the working groups regarding funding allocations and regulation of funded research. It must also ensure that the Institute generates annual reports documenting its activities and its financial status. We note that the CIRM website provides extensive documentation of the agendas and discussions of the public meetings of the ICOC and the working groups. There is a high degree of transparency concerning the governance and operations of the agency.

3.2 Funding of research and research facilities

The primary purpose of the California Institute for Regenerative Medicine is to raise and disburse funds for stem cell research in the state. Grants are made only to California-based research institutions and are funded primarily by state bond issues. All grants are made following peer review of the applications. The Scientific and Medical Research Funding Working Group of the ICOC was established for two purposes. First, it recommends to the ICOC criteria, standards, and requirements for reviewing research applications. Second, using those criteria and standards, the working group reviews grant and loan applications, making funding recommendations to the ICOC for the award of research, therapy development, and clinical trials grants and loans. While this working group contains eight laypeople, only its 15 scientist members score grant and loan award applications for their scientific merit. The Scientific and Medical Research Facilities Working Group was established to award grants and loans for buildings, building leases, and capital equipment. The initiative required that all funded facilities and equipment be located in California and further required that all grantees be non-profit entities. Finally, the initiative required that each grantee secure matching funds equal to at least 20% of the award. The majority of members of this working group are drawn from the membership of the Scientific and Medical Research Funding Working Group. However, those members are augmented by four real estate specialists based in California.

3.3 Regulation of funded research

The political and ethical sensitivities around human embryonic stem cell research make it imperative that public funding of this work is effectively regulated. Towards this end, the Scientific and Medical Accountability Standards Working Group of the ICOC is charged with recommending to the ICOC scientific, medical, and ethical standards for medical research and clinical trials. This includes setting standards for safe and ethical procedures for obtaining materials and cells for research and for appropriate treatment of human subjects in medical research. As well as consisting of five layperson members and nine scientists nationally recognized for their work on human stem cells, the working group also contains four medical ethicists. Along with making regulations to guide funded research, this working group has also been charged with making recommendations to the ICOC for oversight of that scientific work, a topic we discuss next.

Following Lomax, Hall, and Lo (2007) – who were closely involved in developing these regulations – we here highlight four features of the regulatory framework promulgated by the Scientific and Medical Accountability Standards Working Group. First, efforts have been made to encourage institutions and researchers to develop best practices for ethical conduct of stem cell research. Within the United States, each research institution takes primary responsibility for reviewing proposed research projects involving human participants. CIRM requires that a Stem Cell Research Oversight Committee (SCRO) be established in each funded institution. But the regulations concerning the review processes have been left flexible so that the work of the SCRO can be effectively coordinated with the practices of existing research review boards. As well as this, the regulations have been designed to encourage the attainment of high performance standards and documentation of how those are being reached, rather than emphasizing the achievement of minimum standards. This has left a lot of room for development of effective procedure for ensuring informed consent of research participants in a field when knowledge and procedures are advancing rapidly. A focus on minimum standards could lock in ways of doing things that could quickly become obsolete.

Second, the working group sought to avoid imposing on researchers unnecessary regulatory burdens. The working group has done so by isolating areas of research that are novel, versus those where a reasonable amount is known and appropriate ethical procedures have already been developed. This approach means that most effort on the part of both CIRM and the individual research institutes goes into determining appropriate approaches to dealing with ethical concerns in fields of research that have not been tackled before. Such an approach also helps to keep Californian science and science management at the cutting edge.

Third, the Scientific and Medical Accountability Standards Working Group has involved the public in development of its regulations. Here, a virtue has been made out of the requirement that the ICOC operates in a transparent manner. When operations were first being set up in 2005, the working group proposed adoption of the 2005 National Academy of Science Guidelines for Human Embryonic Stem Cell Research as interim regulations. Eight public meetings were held in the following year to facilitate the development of permanent regulations. After receiving public comment at those meetings, the working group made adjustments to regulations and then posted the draft revisions on its website. Those drafts were then open to more comment. The final regulations were also subject to review and approval by the California Office of Administrative Law. In the view of Lomax et al. (2007), this process resulted in a stronger set of regulations that reflected both professional and public input.

Finally, the working group has sought to develop regulations that are consistent with existing laws and ethical guidelines. It is well understood that differences in regulatory guidelines between jurisdictions can create major barriers to the formation of effective scientific teams. To address this problem, the working group decided not to insist on exact conformity with CIRM regulations in all cases. Rather, where ethical guidelines tended to be inconsistent, the working group has undertaken to assess matters on a case-by-case basis, to achieve an effective outcome. Of course, problems cannot be ignored and strict rules set at the state-level must be observed (such as the California prohibition on payment of egg donors). But room often exists for finding effective solutions to problems. Rather than ruling out a fruitful line of research because of a disjuncture between guidelines across jurisdictions, the commitment here is to working to find a way forward.

3.4 Oversight of funded research

Oversight of research can occur through the careful observation of operations at specific sites, by requiring careful systems of reporting and documentation of operations, or by a combination of both. At this relatively early stage in the funding of stem cell research, evidence shows staff at the Institute and members of the Scientific and Medical Accountability Standards Working Group are seeking to develop methods of oversight that are both effective and non-onerous to the funded researchers and institutions. For example, recent meeting discussions illustrate efforts to develop reporting procedures that reduce the need for intensive investigations at the site level. However, it is well-recognized that good record-keeping at the site level can greatly assist investigators, should the need arise to carefully review research processes.¹² Practices of this kind, where the regulators engage in dialogue with research managers, increase the opportunities for best practices to evolve in a cooperative fashion and to be spread across sites (Bardach & Kagan, 2002; Scholz, 1991). The knowledge generated through such practices can also be drawn upon to make incremental improvements to the reporting templates and check-lists developed by the Institute and implemented at the research sites. That appears to be happening in California.

4 Lesson-drawing

Our focus on the governance of stem cell science in California was guided by a place-of-origin analysis of where the leading edge research was being produced. As we acquired more information about the science community in California, the support it has received from the state over decades, and its success in attracting federal funding, the case for focusing on California became more compelling. Of course, we knew that the state had adopted Proposition 71 in 2004 and that this had opened the way for very large investments in stem cell research in the state. But we did not know anything about the details of the governance structures that have been designed to guide those investments. Thus, in accordance with the lesson-drawing approach proposed by Rose (1993, 2005) we chose to focus on a specific governance regime that appeared to have been successful at achieving its intended goals.

In the previous section, we summarized key details of the operations of the California Institute for Regenerative Medicine (CIRM), the Independent Citizens’ Oversight Committee (ICOC), and the Oversight Committee's three working groups. Now, continuing with the lesson-drawing approach, we here make some cause-and-effect claims tying details of the governance regime to the generation of high-quality research outputs. Our purpose is to offer lessons that might assist in both the diagnosis and the design of governance regimes elsewhere. We have not been thinking exclusively about lessons for transfer to the governance of human stem cell research. Rather, our intention is that these lessons could inform analysis of governance structures to facilitate advances in many areas of controversial science, such as genomics and other scientific research falling under the broad rubric of biotechnology. We have drawn four lessons. They cover: first, the initial management of structural choices; second, the inclusion of laypeople in governance; third, transparency of operations; and, finally, creating opportunities for regulatory and oversight practices to remain synchronized with evolving scientific practices.

4.1 Isolate structural design from controversy

The possibility that disagreements will get played out in the design of new governmental agencies is a major concern in the public realm. Moe (1991) has suggested that many agencies “loom as structural nightmares” because compromises have occurred in the design work, as opponents of a new agency have injected “structures fully intended to promote disability and failure” (p. 127). The initiative process in California offers a way for advocates of new agencies to design structures that are less prone to “disability and failure,” simply because there is less need to compromise with opponents in the design work.¹³ Proposition 71 contained detailed descriptions of the structures to be used to govern stem cell research in California. When the initiative won a majority of the popular vote, those details were automatically translated into public law. Of course, inevitably, the details contained in initiatives must involve some compromise, as the backers seek to win wide public support for their ideas. But at no stage do the backers cede ground to opponents and let them get involved in the actual design work.

While the conditions that allowed for the creation of the governance structures guiding the funding, regulation, and oversight of stem cell research in California would be difficult to replicate elsewhere, a useful lesson can be drawn from this case. That is, where possible, advocates of a new governance regime should try to isolate the design work from the bigger set of controversies that might surround the scientific work in question. To this end, several useful strategies can be employed by designers. First, they should develop detailed plans before placing a proposal in the public domain. Second, they should be prepared to manage public controversies so that a clear separation can be drawn between disputes about, say, the morality of a specific scientific practice and efforts to design governance structures. Third, they should incorporate features into the design with the aim of expanding the range of supporters for the proposal. This can reduce the opportunities for opponents to set the agenda on structural design.

4.2 Make room for laypeople in the governance structures

Stem cell science is highly complex and good arguments could be made for keeping the decision-making around governance structures solely in the hands of experts. Indeed, empirical studies have revealed a tendency for elected officials to delegate decisions on the regulation of complex technologies to individuals with relevant expert knowledge (Gormley, 1983; Ringquist, Worsham, & Eisner, 2003). However, governance of stem cell science in California is structured to ensure that all major decisions are informed by interested laypeople. By design, the composition of the Independent Citizens’ Oversight Committee and its associated working groups blends laypeople representing specified disease advocacy groups with experts who variously bring knowledge of stem cell science, medical ethics, and real estate development to the table. One explanation for this composition of the Oversight Committee and working groups is that it was little more than a politically astute move on the part of the authors of Proposition 71 to gain popular support for the initiative. But making room for laypeople in the governance structures can do a lot to improve the quality of decision-making. Here, we focus on three positives of this approach to governance.

First, the presence of laypeople on decision-making bodies forces the experts who are present to make their arguments clearly, in ways that can be understood by non-experts. Often, this effort to achieve clarity improves the quality of the argument being made (Samples, 2002). Further, as observers of the social structures supporting scientific collaborations have noted, clear communication is vital to the advancement of the scientific enterprise (Hara, Solomon, Kim, & Sonnenwald, 2003). Hence, it is good practice in general for experts to be forced out of their comfortable ways of communicating among themselves and find ways to effectively engage with others who, while they might well be experts in their own right, do not share their specialist knowledge and vocabulary. The upshot of this perspective is that the need for experts to communicate effectively with laypeople can serve to improve the quality of decision-making and of scientific communication more generally. As scientists work to communicate effectively with laypeople the chances increase that they will gain the trust of their audience, and that is very important when the reason for that communication in the first place is to contribute to the governance of controversial science.

Second, laypeople spend the bulk of their time communicating with other laypeople. When lay members of a decision-making body have positive experiences on it, they are likely to talk about them. That can help to promote the diffusion among grassroots groups of greater trust for the decision-making process and the experts involved. But laypeople should not be treated simply as potential ambassadors for science among the grassroots. Having their ear to the ground, they can also serve as vital conduits for feeding back into the governance discussions any concerns that they have been noting among members of the groups they represent. As such, laypeople on decision-making bodies can serve as critical friends to the experts involved; helping to keep the experts aware of the broader social context within which the science in question takes place.

Finally, the presence of laypeople on decision-making bodies can encourage public input at meetings. If citizens knew that a decision-making body was composed solely of people with high levels of specific expert knowledge, they might find it intimidating to interact with them or to question their statements. Knowing that laypeople are integral to the decision-making body can change the dynamics of public meetings. The breaking down of barriers between members of the public and members of the decision-making body can promote more open dialogue and the development of trust. The creations of comfortable spaces for public deliberation increases the odds that good decisions will be made (Forester, 1999).

4.3 Promote transparency, minimize secrecy

California has a tradition of requiring high levels of transparency in the operations of public entities.¹⁴ The operations of the California Institute for Regenerative Medicine and the Independent Citizens’ Oversight Committee conform closely to this tradition. Public meetings are regularly scheduled and high levels of information are made available to the public at those meetings and in the transcripts of the meetings that are routinely posted on the CIRM website. Transparency is particularly important in cases where complex systems or processes are concerned. Often controversy can be fuelled by secrecy (Covey, 2006). Although there are good moral reasons why people might disagree about aspects of stem cell science, it is important that suspicions and disputes are not unnecessarily promoted. Creating transparency is a way to reduce public concerns. Of course, there are times when the privacy of human subjects and of researchers themselves should be respected. However, CIRM and the ICOC appear to have found ways to effectively balance the need for minimal levels of secrecy against the need to be as open as possible with taxpayers and concerned citizens. In short, controversial science can often be made much less controversial through efforts to understand and meet the information needs of the public.

4.4 Create opportunities for learning and innovation

It has long been recognized that regulations designed to create improved outcomes in a given set of circumstances at a given time can become counter-productive (Friedman, 1962; McCraw, 1984). That is because regulations are often predicated on current knowledge and they create incentives for conformity rather than incentives to make performance improvements (Schultze, 1977). In the case of stem cell research in California, concerted efforts have been made to develop regulations and oversight practices that perform effectively without creating onerous burdens for researchers and their institutions. The Scientific and Medical Accountability Standards Working Group has allowed institutions drawing funds from CIRM to come to their own decisions about the structure and practices of their Stem Cell Research Oversight Committees and how those committees relate to their broader Institutional Review Boards. The combination of this decentralized decision-making and central monitoring from CIRM creates excellent conditions for encouraging good practice and learning. Keeping decision-making close to where the science is being done raises the likelihood that reviews and oversight of research will be conducted in ways that take specific contextual conditions and concerns into account. In turn, this can create opportunities for learning and for that learning to be communicated back to the CIRM. For its part, through site visits, conversations with institutional representatives, and more formal kinds of monitoring, CIRM officials can become diffusers of incremental improvements and innovations in regulatory compliance across the science system. The key to effectiveness here is the willingness on the part of all concerned to prioritize the advancement of scientific excellence over narrow adherence to rules that might not always make sense. As with the other lessons drawn here, again we see an important role for trust in the promotion of good system outcomes.

The governance of stem cell research in California follows a unique design. That uniqueness is partly a function of the state's political institutions and the structure of the scientific enterprise that has evolved there. Given this, it is unlikely that the Californian model could be precisely followed elsewhere. But replication is distinct from lesson-drawing. The four lessons drawn here are intended to offer guidance for the diagnosis and design of other governance regimes for the funding, regulation, and oversight of controversial science.

5 Conclusion

Developments in genomics and biotechnology have met with a variety of responses from governments operating both at the national and sub-national levels around the world. Among forms of human genomics and biotechnology, human stem cell research has been one of the most controversial. On the one hand, it offers great promise for the development of medical therapies that could effectively treat patients suffering from life-threatening diseases. On the other, the linkage between human reproduction and research on embryonic stem cells has fuelled serious opposition from groups who campaign for the right to life of the human foetus. In this article, we have drawn lessons for governing controversial science by focusing on the governance of stem cell research in California. Stem cell science has raised various issues that have created major public controversy. At the same time, making investments in this science has been justified on the basis of the medical therapies that could result from it and the economic benefits that could accrue to the locations where both the basic science is performed and commercial developments are spun off from it.

The United States has held an unchallenged place as the world leader in the advancement of stem cell science. Within the United States, California has held a strong and consistent place as the location where a significant amount of stem cell research occurs, where state funding has been huge, and where a great deal of careful thought has gone into the design of public policies relating to the governance of this science. Here, we discussed the evolution in California of current governance arrangements. In so doing, we noted how morality politics and the imperatives of economic development have produced policy controversies and how those controversies have influenced subsequent policy design. We then drew out four lessons from the California case concerning the governance of other areas of genomics and biotechnology. Based on this study, we contend that good policy design can address significant public concerns about controversial science without unduly inhibiting advances in the science itself and its applications.

Notes

Manuscript prepared for special issue of Policy and Society on the theme of Policy and Genomics.

1 Source: Authors’ calculations based on Academic Ranking of World Universities 2007, produced by the Institute of Higher Education, Shanghai Jiao Tong University. (http://ed.sjtu.edu.cn/ranking.htm accessed 5 June 2008.) This ranking system was preferred to all others available because it ranks universities by several indicators of academic or research performance, including alumni and staff winning Nobel Prizes and Fields Medals, highly cited researchers, articles published in Nature and Science, articles indexed in major citation indices, and the per capita academic performance of an institution.

2 For a useful summary of relevant evidence, the National Science Foundation's Science and Engineering State Profiles: 2005–07 (NSF 08-314 | August 2008), especially the state profile for California. Available at: http://www.nsf.gov/statistics/nsf08314/.

3 The exception was Israel. One paper published in Science during the period from January 1998 through December 2008 was authored by scientists based in Israel.

4 Source: Authors’ calculations based on Academic Ranking of World Universities 2007, produced by the Institute of Higher Education, Shanghai Jiao Tong University. (http://ed.sjtu.edu.cn/ranking.htm accessed 5 June 2008.) This ranking system was preferred to all others available because it ranks universities by several indicators of academic or research performance, including alumni and staff winning Nobel Prizes and Fields Medals, highly cited researchers, articles published in Nature and Science, articles indexed in major citation indices, and the per capita academic performance of an institution.

5 These differences hold when the United States, which is an obvious outlier, is dropped from the analysis. Indeed, the difference between the groups of countries becomes more statistically significant when the United States is dropped from the analysis because the variance among cases is reduced.

6 We replicated this analysis using evidence from our place-of-original analysis of articles appearing in Nature from January 1998 through December 2008. The average number of publications for the 23 states hosting one or more top ranked universities was about 4. This compares with an average of close to 0 for the 27 states without a top ranked university (t =2.18, d.f.=1,48, p <0.018, one-tailed test).

7 Source: Authors’ calculations from two sources. (1) National Institutes of Health Research Portfolio Online Reporting Tool, NIH dollars awarded per state in 2008. (http://report.nih.gov/award/trends/State_Congressional/StateOverview.cfm accessed 24 March 2009.) (2) U.S. Bureau of the Census estimated population for each state as of July 2008. (http://factfinder.census.gov/ accessed 24 March 2009.)

8 We replicated this text using our data on publications in Nature. In the 17 states where scientists published articles on stem cells in Nature between January 1998 and December 2008, the average amount of NIH funds received per capita was $84, versus $47 per capita in the 33 states where no scientists published articles on stem cells in Science (n =50, d.f.=1,48, t =2.31, p <0.013, one-tailed test).

9 As of 2008, 10 states had agreed to fund stem cell research. These were California, Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New Mexico, New York, Ohio, and Wisconsin. For more detailed analysis of the reasons why states have funded stem cell research, see Mintrom (2009).

10 Thomson's breakthrough research was not eligible for funding by the National Institutes of Health. To conduct this work, Thomson had established a separate laboratory at the University of Wisconsin supported by private funding from the Geron Corporation of Menlo Park, California and the Wisconsin Alumni Research Foundation.

11 On 9 March 2009, President Barack Obama announced that he would remove restrictions on federal funding for embryonic stem cell research. He did not offer details of the changes he intended to make. Among other things, he stated: “The majority of Americans – from across the political spectrum, of all backgrounds and beliefs – have come to a consensus that we should pursue this research. That the potential it offers is great, and with proper guidelines and strict oversight, the perils can be avoided”.

12 Note these comments from Geoffrey Lomax at the Regular Meeting of the Scientific and Medical Accountability Standards Working Group held on 12 December 2008 “…Just to remind folks, we have been implementing our compliance program. We’ve developed protocols for evaluating compliance with the regulations and administrative requirements. A big piece of that is going out and looking at the institutions, how they’ve established oversight committees, and looking to ensure—we go in and look for assurance that they are implementing, the SCRO [Stem Cell Research Oversight] committees, our regulations as described. As of December 2008, we’ve visited five sites which represent 42 percent of CIRM funding. We’ve, in general, found substantial compliance with the regulations. We have identified some areas where we’ve seen room for improvement, and we’ve communicated that information to the grantees. In addition, we’re using this opportunity to develop a series of guidance documents and technical assistance fact sheets on issues; for example, like what the ideal oversight SCRO approval letter would look like in terms of documenting the approval, the types of cell lines approved, etc. So it is really giving us an opportunity to interact directly with the regulated community and identify ways in which we can be most effective in terms of regulations, assurance, and documentation. And our goal is to visit all sites with funding greater than $5 million by the first half of next year [2009], and we’ll be looking forward to providing you with a full report once we’ve completed our first cycle.” Retrieved from http://www.cirm.ca.gov/workgroups/ on 30 March 2009.

13 To date, limited analysis has been done of the comparative effectiveness of public policies and public agencies promulgated via initiative rather than the legislative process. However, in a survey of the literature, Lupia and Matsusaka (2004) note that the extant literature portrays in quite positive terms the effectiveness of public policy made via initiatives.

14 The Bagley-Keene Act of 1967, officially known as the Bagley-Keene Open Meeting Act, mandates open meetings for California State agencies, boards, and commissions in order to facilitate accountability and transparency of government activities and protect the rights of citizens to participate in State government deliberations. Legislation enacting the California Public Records Act (CPRA) was signed in 1968. The fundamental precept of the CPRA is that governmental records shall be disclosed to the public, upon request, unless there is a specific reason not to do so.