Click for next page ( 14


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 13
1 Introduction and Context On November 2, 2004, Proposition 711 (The California Stem Cell Research and Cures Act, reproduced in Appendix C) was adopted by the voters of California. Its purpose was to provide substantial state support for a comprehensive in-state stem cell research program or, more broadly speaking, to make a significant investment in biomedical research within the field of regenerative medicine in California. Proposition 71 also amended the state constitution to provide freedom to conduct pluripotent and progenitor stem cell research and established a distinctive model of both governance and long-term finance for this publicly financed activity in biomedical research.2 In 2005, the California Institute for Regenerative Medicine (CIRM), charged by Proposition 71 with determining the most effective means of distributing $3 billion in state funds for stem cell research over at least 10 years, was created and began its operations. CIRM’s principal aims were to accelerate certain critical aspects of the science of regenerative medicine, emphasizing pluripotent stem cell and progenitor cell research and other vital medical technologies, and its translation into the treatment of a spectrum of currently intractable human diseases. In addition, CIRM sought to establish California as one of the world’s principal hubs in this area of biomedicine.3 Under the terms of Proposition 71, the Institute was to be governed by an Independent Citizens Oversight Committee (ICOC). In both its formation and its ongoing operations, CIRM has sought advice from a wide range of sources and has been the subject of a series of external evaluations. During the initial campaign for Proposition 71, the California Research and Cures Coalition, comprising the principal advocates for Proposition 71, consulted from time to time with the National Academy of Sciences (NAS) and the Institute of Medicine (IOM), as well as others, as they designed the proposition’s details. Once established, CIRM again consulted the NAS and IOM for help in establishing the initial set of ethical guidelines for its research program (IOM, 2005). In addition, a number of studies have been commissioned to assess the potential economic impact of CIRM’s activities. One such study, by the Analysis Group (Baker and Deal, 2004), preceded the 1 California Stem Cell Research and Cures Initiative, Proposition 71 (2004) (codified at California Health and Safety Codes § 125291.10-125291.85). 2 In September 2002, California had enacted a law to permit research involving human embryonic stem cells. California Health and Safety Codes § 123440, 24185, 12115-7, 125300-320. 3 Operations were delayed for more than a year by various legal challenges to Proposition 71, but the courts of California ruled decisively against these challenges. During this delay, CIRM initiated its operations through financing provided by private philanthropy and a loan from the State of California. PREPUBLICATION COPY: UNCORRECTED PROOFS 1-1

OCR for page 13
1-2 THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE Institute’s establishment, and two others (an update by the Analysis Group [Baker and Deal, 2008] and an independent study by Jose Alberro [2011]) were completed more recently. In 2009, California’s Little Hoover Commission, responding to a suggestion by two California legislators, undertook an evaluation of CIRM’s governance structure, its conflict of interest policies, and its responsibilities in the area of accountability.4 The Commission issued a report suggesting some significant changes in these areas, only a few of which CIRM adopted (LHC, 2009).5 In addition, every 2 years, as required by California law, CIRM must report on the quality of its system of internal control. In 2012, as required under Senate Bill (SB) 10646 (2010, also reproduced in Appendix D), which amended certain provisions of Proposition 71, CIRM underwent an independent performance review aimed at evaluating its administrative procedures and its compliance with various responsibilities as laid out in both Proposition 71 and SB 1064 (Moss Adams, LLP, 2012). Finally, in 2010 CIRM convened a broad-based External Advisory Panel (EAP) comprising a distinguished international group of scientists, industry representatives, and global health leaders to assess the broad nature of CIRM’s scientific program and future plans (EAP, 2010). The EAP’s report encouraged CIRM to continue its programs, but with a sharper emphasis on moving research in regenerative medicine toward clinical applications. Reports resulting from these various reviews have in general been highly positive, although, as noted above, the Little Hoover Commission made a series of recommendations, some echoed in the recent performance review (Moss Adams, LLP, 2012), regarding more efficient/effective governance and administration. STATEMENT OF TASK AND STUDY APPROACH In 2010, as CIRM approached the midpoint of its 10-year state funding horizon, it asked the IOM to provide an independent assessment of the process through which it was established and of its programmatic and scientific scope, organizational and management systems, funding model, and intellectual property policies. The IOM Committee on a Review of the California Institute for Regenerative Medicine, comprising experts in developmental biology, stem cell research, research administration, bioethics, economics, business administration, finance, program evaluation, intellectual property, consumer perspectives, and policy, was assembled in 2011 to critically review the Institute and produce a report containing recommendations for ways in which it could improve its performance. The committee’s statement of task is presented in Box 1-1. 4 The Little Hoover Commission is an independent state oversight agency whose mission is to investigate state government operations with the aim of promoting efficiency, economy, and improved service. The Commission selects its own agenda in deciding which government operations it wishes to study. 5 CIRM’S response to the Little Hoover Commission’s report (CIRM, 2012). 6 California Legislature (Sen. Bill No. 1064), approved by Governor September 30, 2010. Filed with Secretary of State September 30, 2010. PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
INTRODUCTION AND CONTEXT 1-3 BOX 1-1 Statement of Task The California Institute for Regenerative Medicine (CIRM) asked the Institute of Medicine (IOM) to convene a committee to produce a report providing an independent assessment of CIRM’s programs, operations, strategies, and performance since 2005. Specifically, the committee was charged with addressing the following questions:  CIRM’s initial processes—What can be learned from the history and process of building consensus in the public and scientific communities to support the inception and work of CIRM?  CIRM’s programmatic and scientific scope—Does CIRM have the portfolio of projects and grant opportunities necessary to meet its scientific goals? How can CIRM improve upon its existing array of programs? What additional programs and initiatives are recommended to meet its goals? What impacts have been seen from international agreements? Does CIRM’s scientific strategic plan address the range of relevant issues in regenerative medicine within CIRM’s mandated scope of work?  CIRM’s organizational and management systems—Are the internal organizational and management systems (in particular the board and working group structures and operations, the peer review system, the conflict of interest guidelines, and the grants management system) effective in working toward the institute’s scientific goals? Are the systems that are in place scientifically and ethically valid and rigorous? Do they achieve the level of transparency and the level of stakeholder and scientific community involvement needed to meet the institute’s public responsibilities and scientific goals?  CIRM’s funding model—Has the funding model for CIRM had an impact on the work of the institute? What are the advantages of CIRM’s model for covering long-term costs of medical research? Could aspects of this funding model serve as a paradigm for other states or countries? What has been the economic impact of CIRM’s research and facilities awards and grants?  CIRM’s intellectual property policies—What are the strengths and weaknesses of CIRM’s policy for sharing revenue generated by intellectual property? How does this model compare to the model governing federally-supported research? The principal objective of this review was to ensure that all aspects of CIRM’s operations are functioning at peak performance. The committee was asked to provide recommendations regarding short-, medium-, and long-term actions that could improve the performance of CIRM. The committee used several methods for data collection. First, it held five meetings and hosted three public meetings (one in Washington, DC, and two in California) to gather information on topics related to the study charge and to hear stakeholder perspectives on the operations of CIRM. The committee also received an extensive set of documents from CIRM describing its history, structure, operations, and policies; reviewed previous reports, detailed above, evaluating various aspects of the Institute; and gathered information through several PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
1-4 THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE questionnaires.7 In addition, committee members visited three institutions that receive CIRM funding for facilities, research, and training to review some of the facilities funded by CIRM, to speak with both CIRM-funded investigators and the leaders of these institutions, and to learn firsthand about the CIRM-funded work being conducted.8 The study methods are described more fully in Appendix A. The purpose of this report is to present the committee’s assessment of CIRM’s organization, policies, and performance. The committee’s findings, conclusions, and recommendations are intended to address particular aspects of CIRM’s operations and to assist the Institute in its future planning. Additional audiences for the report include other entities that fund biomedical research, policy makers, researchers, and the public. It is important to be clear that this committee was not asked to assess the wisdom of the California voters in passing Proposition 71. However, many of the detailed provisions of Proposition 71 directly impact aspects of CIRM’s operations that the committee was asked to evaluate in its statement of task. For example, Proposition 71 details certain aspects of CIRM’s management and governance structure, as well as its funding model. The committee was not charged with rigorously evaluating the details of CIRM’s scientific contributions, specific grant awards, or its impact on the field of regenerative medicine; however, the committee did examine CIRM’s overall scientific priorities and the quality of the processes instituted to guide its funding priorities and decisions. In summary, the conclusions expressed throughout this report address some of the unique aspects of CIRM’s beginnings, its governance structure, its policies, and its ongoing efforts. The report considers the vitality and success of the important dimensions of the Institute’s activities and presents the committee’s assessment of whether this is a useful model for others to consider. Finally, the report is intended to help CIRM consider the best path forward as it works to meet its obligations to the citizens of California and the field of regenerative medicine. The remainder of this chapter briefly reviews the character and potential of stem cell research and the controversy that provides the historical context for the creation of CIRM. CHARACTER AND POTENTIAL OF STEM CELL RESEARCH Research on stem cells remains an important area of biomedical research because of its anticipated potential to yield new and more effective treatments for a wide variety of diseases. Stem cells have the critical characteristic that they can self-renew and also differentiate into a variety of specialized cell types (NIH, 2010; The National Academies, 2009). There are two major types of stem cells—adult and embryonic. Adult stem cells, sometimes referred to as “tissue-specific” or “somatic,” generally are thought to have more limited developmental potential—for example, giving rise only to cells within a particular tissue or organ. Human embryonic stem (hES) cells are pluripotent cells derived from the inner cells of the 3- to 5-day- old embryo (the blastocyst), which give rise to the entire body of the human organism (Thomson et al., 1998) and retain the potential to differentiate into almost all types of cells (ISSCR, 2011). More recently, scientists have been able to reprogram differentiated adult cells into cells that closely resemble hES cells (Takahashi and Yamanaka, 2006; Takahashi et al., 2007); however, the full therapeutic and scientific potential of these induced pluripotent stem (iPS) cells requires 7 The committee wishes to acknowledge the assistance of CIRM staff in expeditiously assembling a great deal of information for this study. 8 The institutions visited were the University of California, San Francisco; Stanford University; and the University of California, Davis. PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
INTRODUCTION AND CONTEXT 1-5 continued exploration (Robinton and Daley, 2012). Both hES and iPS cells are often referred to as pluripotent stem cells because they have, in principle, the capability to give rise to all adult tissues. The ability of these different types of stem cells to self-renew and differentiate into more mature cell types is the foundation of the regenerative medicine field, providing hope for repairing or supplementing a patient’s damaged tissue (Robinton and Daley, 2012). Furthermore, stem cell therapy, if successfully developed, could potentially treat diseases, such as Parkinson’s disease, type 1 diabetes, and spinal cord injury, for which current forms of therapy are less than adequate, and although even more challenging, could potentially be used in treatment of other serious diseases that historically have had poor outcomes, such as Alzheimer’s disease, stroke, and some types of cancer. Another use of stem cells is to help test and develop new drugs (Grskovic et al., 2011). Since pluripotent stem cells can differentiate into a variety of differentiated cell types, drug testing can be performed on these cells before clinical trials are conducted on human subjects, making it possible to test the drugs’ effectiveness and adverse effects more efficiently, particularly in patient-specific stem cell lines (Yu and Thomson, 2010). Pluripotent stem cells (both hES and iPS) derived from patients with specific diseases have also proved useful in studying disease pathogenesis. This has been clearly demonstrated for “cell- autonomous” diseases such as long QT syndrome, in which cardiomyocytes differentiated from patient-specific pluripotent stem cells display the abnormal electrophysiologic phenotype characteristic of the disease. Regenerative medicine can be defined as the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. This can be done through a variety of approaches including the replacement of tissue function with synthetic constructs (artificial organs) an using cellular therapies such as stem cells or genetically modified cells to generate new tissues and organs (ESF, 2012). THE STEM CELL CONTROVERSY Since the derivation of hES cells involves the destruction of human embryos, the scientific community and others immediately recognized that the use of these cells raises important ethical questions regarding the moral status of the embryo; whether research that involves the destruction of embryos is morally acceptable; and if so, whether such research should be funded by federal or state governments. Given the continuing and sharply different perspectives on these key ethical issues, the controversy regarding the appropriateness of public funding for research that requires creating and/or using hES cells has remained unresolved. The tension between this unsettled ethical controversy and the perceived potential of this new area of biomedical research is reflected in the fact that Presidents Clinton, George W. Bush, and Obama all found it necessary to clarify their differing views on these matters by issuing a series of policy guidelines governing the provision of federal funds for research that involves creating and/or using hES cells.9 9 See National Institute of Health Guidelines for Research Using Human Pluripotent Stem Cells (65 Fed. Reg., 51976-51981 [2000]) for the Clinton Administration’s policy; Address to the Nation on Stem Cell Research from Crawford, Texas (37 Weekly Comp. Pres. Doc. 1149 [August 9, 2001]) for the Bush Administration’s policy; and Removing Barriers to Responsible Scientific Research Involving Human Stem Cells (74 Fed. Reg. 10667 [2009]), and National Institute of Health Guidelines for Human Stem Cell Research Notice (74 Fed. Reg. 32170 [2009]) for the Obama Administration’s policy. PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
1-6 THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE It is also important to recall that the controversy over federal funding of research using human embryos or aborted fetuses predates these more recent developments in stem cell research. Embryo research was, for example, the focus of considerable controversy in the mid- 1990s, which led to the Dickey-Wicker Amendment of 1995 forbidding the expenditure of federal funds for research that created or harmed human embryos. Indeed, as early as the 1960s, scientists were already experimenting with the use of aborted human fetal tissue in an effort to understand human development (e.g., August et al., 1968; IOM, 1994; NIH, 1994). As a matter of policy, however, no federal funding was available for research using human embryos during the administrations of Presidents Regan and George H.W. Bush. This moratorium on federally funded research using human fetal tissue was lifted, with certain restrictions, relatively early in the administration of President Clinton.10 Very soon thereafter, however, President Clinton further clarified his views to ensure that federal funds would not be used for research involving the destruction of human embryos.11 After Thomson and colleagues (1998) had demonstrated the possibility of creating and sustaining hES cell lines, the Clinton Administration, through the National Institutes of Health (NIH), issued guidelines in 2000 for grants funding hES cell research. No federal funding was to be allowed for the creation of new hES cell lines, and in fact, no grants for research with hES cells were issued before the end of the Clinton Administration.12 The administration of George W. Bush took an immediate interest in this controversy, and on August 9, 2001, the President announced that federal funds would be available only for work with hES cell lines that had been developed prior to that date.13 The impact of this new policy was widely debated in the scholarly and disease advocacy communities.14 In fact, because NIH was unable to take the lead in this area, the National Academies convened a committee to draft voluntary guidelines for hES cell research (NRC and IOM, 2005). In March 2009, shortly after taking office, President Obama issued an executive order allowing NIH support for hES cell research to the extent permitted by law. Executive Order 13505—Removing Barriers to Responsible Scientific Research Involving Human Stem Cells— states that the Secretary of Health and Human Services, through the director of NIH, “may support and conduct responsible, scientifically worthy human stem cell research, including human embryonic stem cell (hESC) research, to the extent permitted by law”15 Recognizing the controversial ethical issues involved, the new guidelines, issued in July 2009, contain provisions designed to ensure informed consent from donors, address potential conflicts of interest, and limit federal funding to research on hES cell lines derived from embryos originally created for reproductive purposes. Specifically, the guidelines state that, to be eligible for federal funding, hES cell lines must be created from embryos that were produced for reproductive purposes and 10 National Institute of Health Revitalization Act of 1993, Public Law 103-43, 107 Stat. 122 (1993), 42 U.S.C. § 201. 11 Statement on the Federal Funding of Research on Human Embryos, 30 Weekly Comp. Pres. Doc. 2459 (December 2, 1994). 12 National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells (65 Fed. Reg., 51976- 51981 [2000]). 13 Address to the Nation on Stem Cell Research from Crawford, Texas, 37 Weekly Comp. Pres. Doc. 1149 (August 9, 2001). 14 Approximately 1 month after the President’s announcement, an NAS report and an unpublished NIH analysis both stated that additional hES cell lines would have to be available to federally funded researchers to fulfill the promise of research announced in 2001 (NRC, 2002). In addition, several studies have examined the geographic distribution of publications in the field (e.g., Levine, 2008; Owen-Smith and McCormick, 2006). 15 Removing Barriers to Responsible Scientific Research Involving Human Stem Cells (74 Fed. Reg. 10667 [2009]). PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
INTRODUCTION AND CONTEXT 1-7 are no longer needed for that purpose, that the embryos used to produce the lines must be donated by individuals who sought reproductive treatment and who have given voluntary consent for the embryos to be used for research purposes, and that no payments—cash or in kind—must be offered for the donated embryos. NIH also established a stem cell working group to formulate recommendations for the NIH Advisory Committee to present to the director regarding the acceptability of lines that predate the new guidelines. With the new guidelines in place, 178 hES cell lines have been approved by NIH as being eligible for federal funding (as of August 30, 2012). In August 2009, a suit was filed in United States District Court to block the Department of Health and Human Services (HHS) from implementing the new guidelines on the grounds that they were in violation of the Dickey-Wicker Amendment.16 In August 2010, the court ruled in favor of the plaintiffs and issued a preliminary injunction ordering HHS to cease funding research using hES cells. The Obama Administration appealed this decision to the U.S. Court of Appeals for the District of Columbia Circuit, which resulted, in September 2010, in a preliminary stay of the injunction and then, in April 2011, its reversal. Following this decision, in July 2011, the underlying case was decided in District Court in favor of the Obama Administration. This ruling has been appealed to the U.S. Court of Appeals for the District of Columbia, and as of this writing, a final decision is being awaited. Thus the last decade and a half has seen continuing uncertainty regarding the federal government’s willingness to fund research using hES cells—an ongoing disappointment to those scientists and other citizens who believe the nation is foregoing a highly promising opportunity to relieve human suffering. Given that the federal government has traditionally been the largest source of funding for biomedical research outside of industry and the largest funder of basic research, it appeared to some that the United States was foregoing an important opportunity to be a pioneer in developing the basic research necessary to produce critical new clinical applications. Within industry itself, the uncertainty surrounding both state and federal policies on this research also has produced some hesitancy to enter this research arena. It was in this context that a broad group of California-based scientists, leaders in California higher education, disease advocates, and others mounted the Proposition 71 initiative. Since the early years of this century, when the campaign for CIRM was energetically under way, a great deal of progress has been made in stem cell research. In particular, the increased ability to reprogram adult cells has made the field of regenerative medicine somewhat less dependent on hES cells, a development that is fully reflected both in CIRM’s programs and the field of regenerative medicine worldwide. Indeed, this is one of the key factors that CIRM has considered in updating its strategic plan. These issues are discussed more fully in Chapter 4. ORGANIZATION OF THIS REPORT The remainder of this report presents the results of the committee’s response to its statement of task (Box 1-1), including its findings, conclusions, and recommendations; Table 1-1 shows where in the report each element of the statement of task is addressed. Chapter 2 provides an overview of the process by which CIRM was created and the committee’s assessment of what can be learned from this history, as well as the impact of the Institute’s funding model and whether it might serve as a model for other states or countries. This chapter also provides, for 16 Sherely et al. v. Sebelius et al., 686 F. Supp. 2d 1 (D.D.C. 2009). PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
1-8 THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE comparative purposes, a review of analogous efforts by other states. Chapter 3 assesses the effectiveness of CIRM’s governance structure, including issues of conflict of interest. Chapter 4 evaluates CIRM’s scientific and programmatic scope and how the organization can improve its processes and programs to better meet its goals. Finally, Chapter 5 provides an assessment of CIRM’s intellectual property policies. The committee’s findings are presented throughout these chapters; each chapter ends with the committee’s conclusions and recommendations on the respective topic. It is important to note that CIRM is in a constant state of transition in various aspects of its work as it adapts to its own experience, to rapid scientific developments in regenerative medicine, to some public concerns, and to its own concerns regarding its longer-term financial condition. This assessment is as current as the committee could make it, but inevitably some further changes in response to these various influences are under way even as the committee completes this report. TABLE 1-1 Elements of the Study Charge and Chapters Where They Are Addressed Element of Charge Chapter CIRM’s initial processes—What can be learned from the history and process 2 of building consensus in the public and scientific communities to support the inception and work of CIRM? CIRM’s programmatic and scientific scope—Does CIRM have the portfolio 4 of projects and grant opportunities necessary to meet its scientific goals? How can CIRM improve upon its existing array of programs? What additional programs and initiatives are recommended to meet its goals? What impacts have been seen from international agreements? Does CIRM’s scientific strategic plan address the range of relevant issues in regenerative medicine within CIRM’s mandated scope of work? CIRM’s organizational and management systems—Are the internal 3 organizational and management systems (in particular the board and working group structures and operations, the peer review system, the conflict of interest guidelines, and the grants management system) effective in working toward the institute’s scientific goals? Are the systems that are in place scientifically and ethically valid and rigorous? Do they achieve the level of transparency and the level of stakeholder and scientific community involvement needed to meet the institute’s public responsibilities and scientific goals? CIRM’s funding model—Has the funding model for CIRM had an impact on 2 the work of the institute? What are the advantages of CIRM’s model for covering long-term costs of medical research? Could aspects of this funding model serve as a paradigm for other states or countries? What has been the economic impact of CIRM’s research and facilities awards and grants? CIRM’s intellectual property policies—What are the strengths and 5 weaknesses of CIRM’s policy for sharing revenue generated by intellectual property? How does this model compare to the model governing federally- supported research? PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
INTRODUCTION AND CONTEXT 1-9 REFERENCES Alberro, J. 2011. Economic impact of research funded by the California Institute for Regenerative Medicine. http://www.cirm.ca.gov/files/PDFs/Publications/Economic_Impact_March_2011.pdf (accessed July 2, 2012). August, C. S., F. S. Rosen, R. M. Filler, C. A. Janeway, B. Markowski, and H. E. Kay. 1968. Implantation of a foetal thymus, restoring immunological competence in a patient with thymic aplasia (Digeorge’s syndrome). Lancet 2(7580):1210-1211. Baker, L., and B. Deal. 2004. Economic impact analysis—Proposition 71 California Stem Cell Research and Cures Initiative. http://www.analysisgroup.com/uploadedFiles/News_and_Events/News/Proposition_71_report.pdf (accessed July 2, 2012). Baker, L., and B. Deal. 2008. CIRM—Interim economic impact review. http://www.cirm.ca.gov/pub/pdf/EcoEval_091008_rpt.pdf (accessed July 2, 2012). CIRM (California Institute for Regenerative Medicine). 2012. CIRM’s response to the Little Hoover Commission report on CIRM. http://www.cirm.ca.gov/files/meetings/pdf/2009/081909_item_7A.pdf (accessed July 13, 2012). EAP (External Advisory Panel). 2010. Report of the External Advisory Panel. http://www.cirm.ca.gov/files/PDFs/Administrative/CIRM-EAP_Report.pdf (accessed July 2, 2012). ESF (European Science Foundation). 2012. Regenerative Medicine (REMEDIC). http://www.esf.org/nc/activities/research-networking-programmes/medical-sciences-emrc/current-esf- research-networking-programmes/regenerative-medicine-remedic.html (accessed November 14, 2012) Grskovic, M., A. Javaherian, B. Strulovici, and G. Q. Daley. 2011. Induced pluripotent stem cells— opportunities for disease modeling and drug discovery. Nature Reviews Drug Discovery 10(12):915- 929. IOM (Institute of Medicine). 1994. Fetal research and applications: A conference summary. Washington, DC: National Academy Press. IOM. 2005. Guidelines for human embryonic stem cell research. Washington, DC: The National Academies Press. ISSCR (International Society for Stem Cell Research). 2011. Stem cell facts. http://www.isscr.org/public/ISSCR08_PubEdBroch.pdf (accessed August 30, 2011). Levine, A. D. 2008. Identifying under- and over-performing countries in research related to human embryonic stem cells. Cell Stem Cell 2(6):521-524. LHC (Little Hoover Commission). 2009. Stem cell research: Strengthening governance to further the voters’ mandate. http://www.lhc.ca.gov/studies/198/report198.html (accessed July 2, 2012). Moss Adams, LLP. 2012. California Institute for Regenerative Medicine FY 2010-2011 performance audit. http://cirm.ca.gov/files/meetings/pdf/2012/052412_item_6.pdf (accessed July 13, 2012). The National Academies. 2009. Understanding stem cells: An overview of the science and issues from The National Academies. http://dels.nas.edu/resources/static-assets/materials-based-on- reports/booklets/Understanding_Stem_Cells.pdf (accessed August 30, 2011). NIH (National Institutes of Health). 1994. Report of the Human Embryo Research Panel. Bethesda, MD: NIH. NIH. 2010. Resource for stem cell research: Glossary. http://stemcells.nih.gov/StemCells/Templates/StemCellContentPage.aspx?NRMODE=Published&NR NODEGUID={3C35BAB6-0FE6-4C4E-95F2- 2CB61B58D96D}&NRORIGINALURL=%2finfo%2fglossary.asp&NRCACHEHINT=NoModifyGu est#stemcells (accessed August 30, 2011). PREPUBLICATION COPY: UNCORRECTED PROOFS

OCR for page 13
1-10 THE CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE NRC (National Research Council). 2002. Stem cells and the future of regenerative medicine. Washington, DC: The National Academies Press. NRC and IOM. 2005. Guidelines for human embryonic stem cell research. Washington, DC: The National Academies Press. Owen-Smith, J., and J. McCormick. 2006. An international gap in human ES research. Nature Biotechnology 24(4):391-392. Robinton, D. A., and G. Q. Daley. 2012. The promise of induced pluripotent stem cells in research and therapy. Nature 481(7381):295-305. Takahashi, K., and S. Yamanaka. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663-676. Takahashi, K., K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861- 872. Thomson, J. A., J. Itskovitz-Eldor, S. S. Shapiro, M. A. Waknitz, J. J. Swiergiel, V. S. Marshall, and J. M. Jones. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145- 1147. Yu, J., and J. A. Thomson. 2010. Embryonic stem cells. http://stemcells.nih.gov/info/Regenerative_Medicine/2006chapter1.htm (accessed July 2, 2012). PREPUBLICATION COPY: UNCORRECTED PROOFS