Connecticut Stem Cell

Transcription

1 Connecticut Stem Cell Research Program Accomplishments February 2013 A Report By The Connecticut Academy of Science and Engineering For The Connecticut Department of Public Health and Connecticut Innovations

2

3 Connecticut Stem Cell Research Program Accomplishments A Report By The Connecticut Academy of Science and Engineering Origin of Inquiry: The Connecticut Department of public Health Connecticut Innovations Date Inquiry Established: september 3, 2012 Date Response Released: february 21, 2013 Copyright, Connecticut Academy of Science and Engineering, Inc. All rights reserved

4 This study was initiated at the request of the Connecticut Department of Public Health and Connecticut Innovations, Inc., on September 3, The project was conducted by an Academy Study Committee with the support of Study Manager Maria Borowski, MA. The content of this report lies within the province of the Academy s Biomedical Research Technical Board. Martha Sherman, the Academy s Managing Editor, edited the report. The report is hereby released with the approval of the Academy Council. richard H. Strauss executive Director ii

5 MEMBERS OF THE STUDY COMMITTEE ON connecticut stem cell research program accomplishments Jane E. Aubin, PhD Chief Scientific Officer and Vice-President Research and Knowledge Translation Canadian Institutes of Health Research Troyen Brennan, MD (Academy Member Corresponding) Executive Vice President and Chief Medical Officer CVS Caremark Charles Jennings, PhD Director, McGovern Institute Neurotechnology (MINT) Program MIT Matthew Kohn, PhD NYSTEM Scientific Officer New York State Department of Health Wadsworth Center Jeanne F. Loring, PhD Professor of Developmental Neurobiology Director, Center for Regenerative Medicine Department of Chemical Physiology, California Campus The Scripps Research Institute STUDY MANAGER Maria Borowski, MA, Project Associate for the Cancer Center of Excellence University of Massachusetts Medical School ACADEMY PROJECT STAFF Richard H. Strauss, Executive Director Terri Clark, Associate Director Ann G. Bertini, Assistant Director for Programs iii

6 iv

7 Table of Contents table of contents...v EXECUTIVE SUMMARY... vii I. introduction...1 II. The Connecticut stem cell research program...5 III. findings...13 IV. recommendations...31 V. references...35 Appendices Appendix A: CONNECTICUT STEM CELL PROGRAM RELATED WEBSITES...37 Appendix B: REQUEST FOR PROPOSAL CONTENT AND REVISIONS: Appendix C: CORE FACILITIES QUESTIONNAIRES...58 Appendix D: PRINCIPAL INVESTIGATOR SURVEY Appendix E: PRINCIPAL INVESTIGATOR SURVEY RESPONSES Appendix F: ALL PROPOSALS AWARDED TO DATE v

8 vi

9 executive summary Executive Summary Stem cell research has the potential for significant benefits to human health. Scientists are exploring the use of stem cells for the growth and development of tissues and organs, developing new drugs and studying genetic diseases. In 2005, Connecticut joined California and New Jersey as the only states to allocate public funds for stem cell research (Public Act ). The Connecticut Stem Cell Research Program was appropriated $20M for grants-in-aid for embryonic or human adult stem cell research. Additionally, this act allocated a total of $80M to be used over the course of seven years ( ) from the state s Tobacco Settlement Fund to support additional stem cell research. The stated purpose of the program is to support the advancement of embryonic and/or human adult stem cell research in Connecticut. While the political and scientific environments of today are quite changed from when the act was adopted, the need for funding stem cell research has not diminished. At year six of the Connecticut Stem Cell Research Program, the Connecticut Department of Public Health (DPH) and Connecticut Innovations (CI) asked the Connecticut Academy of Science and Engineering (CASE) to conduct an analysis of the accomplishments of the program, and to report findings and recommendations to DPH and CI. Connecticut Stem Cell Research Program DPH is tasked with overseeing the Connecticut Stem Cell Research Program and CI provides administrative support. The act enabling the program also mandated the creation of the Stem Cell Research Advisory Committee (SCRAC that is chaired by the DPH commissioner. The committee is comprised of experts from the fields of stem cell research, bioethics, embryology, genetics, cellular biology and business or financial investments. A Stem Cell Research Peer Review Committee also was mandated for the purpose of reviewing all grant applications for scientific and ethical merit and to make recommendations on grant recipients to the SCRAC. Five types of proposals have been accepted for funding consideration over the course of the program, each with its own criteria and award amounts: Core Facilities Established Investigators Group Projects, including Disease Directed Collaboration Group Projects (starting in 2011) Hybrid (in 2006 only) Seed vii

10 executive summary Review of Accomplishments To assess the stem cell research accomplishments, stem cell research leaders at each institution awarded grant funding completed a questionnaire and were interviewed, leaders of the Connecticut stem cell core facilities completed a questionnaire, and every Principal Investigator (PI) with grant funding awarded up through 2011 was asked to complete a survey. Notably, for the PI survey, a 98% response rate was achieved. Institutions and PIs reported on both direct accomplishments (i.e., an accomplishment as a result of a project funded by the program) and indirect accomplishments (i.e., an accomplishment where a resource, such as a core facility, was used for research or results from a funded project allowed researchers to acquire additional funding to continue research from other sources). Therefore, the accomplishments and outcomes cited in this report represent both direct and indirect accomplishments cited by the institutions and PIs surveyed for this study. Additionally, since accomplishments and outcomes of project research are for the most part reported following completion of a project, it is important to note that at the time of this study, the end of 2012, only 52% of grants awarded funding through 2011 had been completed. To better assess the accomplishments and outcomes of the Connecticut Stem Cell Research Program moving forward, it is suggested that metrics for grant reporting and program review should be established and used on an ongoing basis. Grant reporting and program review requirements should be provided in advance to institutions and PIs, with such requirements memorialized in grant assistance agreements. This will assure consistent information is collected and reported for analysis. In summary, accomplishments include leveraging funding received from the Connecticut Stem Cell Research Program to pursue/obtain additional funding for research from other sources; contributions and research outcomes in the form of published papers, new methodologies, etc. and direct achievements including patent applications, new technology, etc.; creation of new jobs in the state of Connecticut to support stem cell research; and development of partnerships and collaborations. Major accomplishments of the Connecticut Stem Cell Research Program include 129 grants awarded through 2012, for a total of $68.8M of the $100M allocated for the program. The program s award funding is on target, with the remainder of the original $100M allocation planned to be awarded by Leveraging the funding received from the Connecticut Stem Cell Research Program to pursue/obtain additional funds for stem cell research from other sources. Many of the PIs responded that as a result of the funding they received, they were able to pursue and/or obtain funding to either continue their research or expand their research endeavors. PIs reported the following related to additional funding from other sources: viii

11 executive summary vv vv vv 9 awards were funded and completed. Grant funding sources included the National Institutes of Health (NIH, 2 awards), corporations (3), private foundations (1), and other sources (3). 33 awards are currently being funded with research in-process. Grant award sources include NIH (17), private foundations (7), public foundations (2), Department of Defense (1), National Science Foundation (1), corporations (1) and other sources (4). 21 proposals were awaiting a funding decision as of November Possible grant sources include NIH (12), private foundations (6), public foundations (1), and other sources (2). It is noted that stem cell research institutional leaders, consistent with the results of the PI survey, reported Connecticut Stem Cell Research Program funding awarded to their institutions has been a contributing factor in leveraging stem cell research funding from other sources. Also, one of the SCRAC s objectives, as specified in the program s enabling legislation, was to develop a donated funds program to encourage funding from sources other than state appropriations. In the early years of the program, the development of a donated funds program to leverage state funding was explored. Initial findings were that potential funders would most likely require projects to be funded in an area of their interest. Under this assumption, unless the Connecticut Stem Cell Research Program was prepared to commit funds to the areas of interest of potential donors, the success of a donated funds program would probably be unlikely. In the future, perhaps creative approaches to seeking donated funds to match Connecticut s funding could be explored. The universities receiving Connecticut Stem Cell Research Program funding (University of Connecticut (UConn)/University of Connecticut Health Center (UCHC), Wesleyan University, and Yale University) reported total grant awards for the period of for the following: total institutional scientific research funding; total stem cell research funding; Connecticut Stem Cell Research Program funding; and stem cell research funding from other sources. Table 1-ES shows that for this period, Connecticut Stem Cell Research Program funding was 19.2% of total stem cell research funding awarded to these institutions. This indicates significant leveraging of Connecticut Stem Cell Research Program funding. This table also shows the scale of total stem cell research funding to total scientific research funding, and total Connecticut Stem Cell Research Program funding to total scientific research funding. ix

12 executive summary Table 1-ES: Connecticut Stem Cell Research Program Funding as Compared to Total Stem Cell Research Funding and Total Scientific Research Funding ( ) Period: Total Institutional Scientific Research Funding Total Stem Cell Research Funding Stem Cell Research Funding CT Stem Cell Research Funding Stem Cell Research - Other Sources Total Stem Cell Research Funding v. Total Institutional Scientific Research Funding (%) CT Stem Cell Research Funding v. Total Scientific Research Funding (%) CT Stem Cell Research Funding v. Total Stem Cell Research Funding (%) UConn/ UCHC* $1,258,300,000 $120,558,813 $32,663,813 $ 87,895, % 2.60% 27.09% Wesleyan $ 33,481,000 $ 4,518,278 $ 2,128,278 $ 2,390, % 6.36% 47.10% Yale $3,429,403,018 $233,373,746 $34,054,964 $199,318, % 0.99% 14.59% Total $4,721,184,018 $358,450,837 $68,847,055 $289,603, % 1.46% 19.21% * Note: UConn/UCHC Connecticut Stem Cell Research Funding includes one grant award of $1,290,499 to Chondrogenics in 2011 ($831,185 of this award is sub-contracted to UCHC) x

13 executive summary Contributions and research outcomes: These outcomes included creation of stem cellrelated companies, articles published in peer-reviewed journals, contributions to the general knowledge base in stem cell biology, and the development of outreach and training programs. vv vv vv vv PI s reported 166 peer-reviewed articles and journals, 59 new research methods, 45 new theories, 24 new laboratories, 55 novel human stem cell lines, 17 new practices (clinical, tools, instruments, procedures/techniques), 9 patent applications, 7 software/databases, and 2 licenses, as outcomes of Connecticut Stem Cell Research Program funding. Wesleyan continues to progress on a stem cell-based therapy for Temporal Lobe Epilepsy, as reported at the Biosciences and Economy Forum for the General Assembly Appropriations Committee on September 24, Additionally, Wesleyan s stem cell research leadership reported 18 peer-reviewed research papers/journal articles published and one new stem cell line. Three of the five stem cell-dedicated laboratories at Wesleyan are funded by the Connecticut Stem Cell Research Program. Wesleyan s reported accomplishments/outcomes are those that can be attributed both directly and indirectly to the Connecticut Stem Cell Research Program. Yale stem cell research leadership reported 470 papers published, 192 invention disclosures, 132 patent applications, and 26 licenses obtained. Yale is researching the use of stem cells for treating Parkinson s disease; repairing damage of the central nervous system; building blood vessels to treat congenital heart defects; creating living, growing blood vessels from scratch; and rebuilding a heart. Yale Core Facilities have developed training classes to help support the researchers requesting stem cell lines. To date, approximately 300 Yale-affiliated scientists have been certified in stem cell culture, cell imaging and gene knockdown through the Yale Core Facilities. Yale s Stem Cell Research Center includes 12,776 square feet of laboratory and administrative space in the university s 120,000 square foot Amistad Building. Yale s reported accomplishments/outcomes are those that can be attributed both directly and indirectly to the Connecticut Stem Cell Research Program. UConn/UCHC stem cell leadership reported the start-up of three companies; derivation of four stem cell lines with distribution to 227 recipients in the United States and worldwide; 150 publications, including journal articles, book chapters, public media and presentations; 15 training sessions on human embryonic stem cell (hesc) culture for 100 researchers and graduate students; and production of patient-specific induced pluripotent stem cells (ipscs) using cutting-edge techniques that do not require any manipulation of human embryos. UConn noted in its 2013 Program Report Card for the General Assembly that recently published articles in medical literature cite progress toward treatment of patients with serious health issues, including promising results in cancer, multiple sclerosis, and severe periodontal diseases. UConn s reported accomplishments/ outcomes are those that can be attributed both directly and indirectly to the Connecticut Stem Cell Research Program. The UConn Stem Cell Institute includes 7,600 square feet of laboratory, administrative and incubator space for stem cell research in the 120,000 square foot UCHC Cell and Genome Sciences Building. It is noted that UConn/UCHC s construction/renovation of the xi

14 executive summary vv building was dependent upon the establishment of the Connecticut Stem Cell Research Program. Core Facility Development Yale University established and maintains five state-of-the-art core laboratories that are located at Yale s Stem Cell Research Center in the Amistad Building, including: Human Embryonic Stem Cell (hesc) Core, Cell Imaging Core, Cell Manipulation Core, Genomics Core, and Fluorescence Activated Cell Sorting (FACS) Core. The cores offer key stem cell technologies to Yale stem cell researchers and stem cell laboratories at other institutions in Connecticut. The Core facility has been in operation since 2007 and includes 1,836 square feet of space. Since 2007, the Yale Core Facilities have been awarded $5,300,000 in Core Facility grant funding from the Connecticut Stem Cell Research Program. The UConn Stem Cell Core facility at UCHC (UCHC Core Facility) that is shared with Wesleyan has been in operation since The Core Facility s 3,600 square foot lab space was renovated in 2010, and is located in UCHC s Cell and Genome Sciences Building. Since 2007, the UCHC Core Facility has been awarded $5,650,000 in Core Facility grant funding from the Connecticut Stem Cell Research Program. Creation of new jobs in the state of Connecticut to support stem cell research. Over the funded years of the program, employment and staffing have steadily increased. It was reported in the PI survey response that 222 researchers and support staff supporting their Connecticut stem cell research grant were new to the stem cell research field; and that approximately 92 staff hired to support the grant awards relocated to Connecticut. Development of partnerships and collaborations. PIs reported 15 separate collaborations that were made possible directly from this funding, and when asked about the importance of collaborations, 82 respondents classified it as either very important or important. Activities such as retreats, workshops and conferences are held annually by the stem cell research community in Connecticut. Connecticut also sponsors StemCONN, a major biennial stem cell conference that is attended by stem cell experts from Connecticut, other states and countries. These types of activities provide a collaborative environment for stem cell research in Connecticut. Based on information provided through this study s surveys, interviews and questionnaires, there were no royalty payments due to the state in accordance with provisions of the grant award assistance agreements. In summary, the Connecticut Stem Cell Research Grant Program has increased stem cell research capacity in the state of Connecticut, established stem cell core facilities, attracted research professionals to the state, and created numerous occupation opportunities along the continuum of scientific research-related employment. As noted in this report, basic science comprises most of the funded research grants. The accomplishments identified in this report illustrate that the program is poised to build on these xii

15 executive summary results and move toward clinical translation while maintaining basic research still needed in this emerging field. Recommendations The following recommendations are offered for consideration regarding identifying and reporting on the accomplishments and performance of the Connecticut Stem Cell Research Program to assure accountability of the state s public investment in stem cell research. The recommendations encompass the following: Annual Program Review, Program Administration, Core Facilities, and Funding. 1. Annual Program Review: Conduct an annual review of the Connecticut Stem Cell Research Program to assess program operations, including administrative operations, and proposal peer review and the selection award process; progress of all grantees awarded funding for in-process and completed projects; and overall accomplishments and benefits to the institutions that receive Connecticut Stem Cell Research Program funding. Each institution should be asked to provide an annual report that identifies the overall accomplishments that resulted from Connecticut Stem Cell Research Program funding, including additional grant funding from other sources that can be attributed to the program, an update on recruitment and retention of stem cell-related faculty and staff, infrastructure improvements to support stem cell research, and a projection on the program s continuing benefits for the upcoming year. The purpose of the annual review process would be to adapt award criteria to position the program based on lessons learned, past achievements, and scientific developments; adjust funding levels between the types of grant funding to capitalize on current needs for basic, translational and clinical research; address funding gaps and redirect funds where needed to support research goals; benchmark the program with similar programs in other areas of the country to support decisions including those related to the investment and management of public funds used for scientific research; and identify best practices for management and investment of public funds in support of stem cell research. The requirements of the current grantee Annual Technical and Fiscal Progress Report, and Final Report should be modified to include annual review process metrics and data, to be determined, for grantees and their institutions. This requirement should be included in the annual Request for Proposals and in grantee assistance agreements. It is suggested that the reporting metrics and data be developed in consultation with the stem cell research leadership of the institutions/companies that receive program xiii

16 executive summary funding. Based on initial lessons learned from this review, suggestions for future metrics for reporting on accomplishments and outcomes include the following: Institutional Research Funding: research award funding as presented in this report should continue to be reported annually so as to clearly show the leveraging of state funding with that from other sources, and to show the scale of stem cell research in relation to total scientific research being conducted at participating universities and companies. Financial reporting terminology and periods should be identified and used by all reporting institutions so that consistent and accurate information can be used for analysis. Staffing and Job Creation: Suggested data to be reported include the following: vv vv vv Project staffing and jobs created should be reported on a full-time-equivalent basis Wages paid, which would be useful for conducting an economic impact analysis of the program in the future New staff relocating to Connecticut as a result of project funding Training Programs: number and types of training programs provided, and the number of participants and where they are from Accomplishments and Outcomes: Many research accomplishments and outcomes occur after the completion of a project, and therefore after a final project report is submitted by the PI. Therefore, consideration should be given to requiring ongoing annual reporting by PIs for grants that have been completed for as long as the program continues and is subject to regular review or for a period of time as determined, with this requirement being a condition of grantee assistance agreements. 2. Program Administration: Program staff designated to manage and oversee the Connecticut Stem Cell Research Program should continually seek to improve the administration of the program and bring uniformity to the grant funding procedures and annual reporting processes. Staff would manage program operations; identify key high-level metrics for the annual review of program accomplishments and administrative performance, in consultation with the program s leadership, including the SCRAC, and the Peer Review Committee; manage the annual review process, including reporting to the SCRAC, state agencies, CGA, research institutions, and others as appropriate; establish relationships between states and/or institutions based on a mutual need for the sharing and reporting of common metrics in collaboration with stem cell researchers and institutional leaders; and research best practices for scientific research grant funding, economic development, and institutional practices and processes in collaboration with stem cell researchers and institutional leaders. xiv

17 executive summary 3. Core Facilities: Consistent with the Core Facilities award goals as described in the most recent Request for Proposals, the Core Facilities at the Yale Stem Cell Center and the Stem Cell Core at UCHC should continue to transition from a reliance on Connecticut Stem Cell Research Program funding to a self-sustaining enterprise serving a broader and deeper range of users, including researchers and labs from other institutions, businesses and entities within the state, regionally and nationally to further support both continued scientific progress in the stem cell field and economic development. Connecticut s core facility administrators should assess user satisfaction with current core facility services and technology and identify services and technology that may be needed in the future; increase collaborative activities between the leaders of the core facilities to ensure that future activities are explored and agreement reached on joint strategies to efficiently make these activities available, while respecting the need for each core facility to focus on approaches unique to their institution s strategic plan; implement outreach plans to increase visibility and use of the facilities by researchers, students and educators, and the general public; and seek to increase the share of core facility revenue from fee-based services and other grant funding sources. 4. Funding: Enact legislation to stabilize research funding to further strengthen the state s preeminence in the stem cell field for a sufficient period of time to enable research institutions and others receiving Connecticut Stem Cell Research Program funding to commit to expand infrastructure necessary for stem cell research; increase the capacity of institutions to leverage funding from other sources; and recruit and retain stem cell researchers and staff It is suggested that the legislation provide for a multi-year (such as five years), rolling funded program that would require legislative action to terminate the program. Termination would only take effect following a trailer of the full funded period (i.e., in the case of a 5-year program, then at the end of the 5 th year so as to provide for a commitment of 5 years of funding prior to termination taking effect). Also, consideration should be given to including in the legislation a formula to determine the annual level of funding to be provided, such as with the first five years at a set level, with each subsequent year then being increased at a rate of x%, or to provide the General Assembly with the option to increase such annual amount of funding by a to-bedetermined inflation factor. Concluding Remarks An important aspect of the state s economic development strategy is to further strengthen the state s competitive position in scientific research and development through its support of biomedical and stem cell research, and expansion into genomics and personalized medicine, as evidenced by 2013 legislation proposed by the governor. xv

18 executive summary The state should consider establishing one entity responsible for administering the state s public investments in scientific research-related grant funding, including the existing biomedical and stem cell research programs as well as the proposed genomics research initiative, and others as may be determined. A centralized administrative structure would effect efficiencies in management, establish a source for scientific research policy advice, and bring uniformity to the grant funding procedures and annual reporting processes to assure accountability of public funding of the state s scientific research initiatives. xvi

19 introduction I. INTRODUCTION In 2005, Connecticut joined California and New Jersey as the only states to have passed legislation to use public funds for embryonic stem cell research. Public Act , entitled An Act Permitting Stem Cell Research and Banning the Cloning of Human Beings, was approved by the General Assembly and signed into law by Governor M. Jodi Rell on June 15, 2005, and incorporated into the Connecticut General Statutes. The act appropriated $20 million for grants-in-aid for embryonic or human adult stem cell research. Additionally, this act allocated a total of $80 million to be used over the course of seven years ( ) from the state s Tobacco Settlement Fund to support additional research through the Stem Cell Research Fund [Connecticut Stem Cell Research Program, 2012]. The stated purpose of this program is to support the advancement of embryonic and/or human adult stem cell research in Connecticut [RFP, 2012] The purpose of this act was to fill a void in funding for stem cell research due to the federal ban on embryonic stem cell research imposed by executive order of President George W. Bush at that time, as well as to secure Connecticut s place as a leader and resource in this burgeoning field. The act also mandated the creation of advisory and peer review committees with the commissioner of the Connecticut Department of Public Health (DPH) serving as chair of the Stem Cell Research Advisory Committee (SCRAC). SCRAC members are appointed by the Connecticut General Assembly (CGA) and the governor, and the committee is composed of experts from the fields of stem cell research, bioethics, embryology, genetics, cellular biology and business or financial investments. When this committee was created, in accordance with enabling legislation, SCRAC was given the following three objectives: [Connecticut Stem Cell Research Program - Committees] develop and oversee the stem cell research grants-in-aid program develop a donated funds program to encourage funding from sources other than state appropriations promote for-profit and not-for-profit stem cell and related research in the state Since its inaugural meeting on November 29, 2005, the primary focus of the SCRAC has been awarding grants-in-aid to eligible institutions in a fair, transparent, and timely manner. This was important for creating and sustaining a vibrant stem cell research community in the state, for the state s ability to administer the funds, and to establish a strong foundation for continued support. Connecticut Innovations, Incorporated (CI) serves as administrative staff for the program on behalf of DPH and SCRAC. CI responsibilities include conducting the annual RFP process including reviewing grant applications for compliance with terms and conditions of requests for proposals; and 1

20 introduction serving as the fiduciary agent for the program, including preparing and executing assistance agreements and assuring grantee compliance with the terms and conditions of the agreements. The legislation for the Stem Cell Research Program also established a Stem Cell Research Peer Review Committee. The purpose of this committee is to review all grant applications for scientific and ethical merit and make recommendations on grant recipients to the SCRAC. Members are appointed by the DPH commissioner, for two- or four-year terms, and have knowledge, understanding and experience of the ethical and scientific implications of embryonic and adult stem cell research. To avoid potential conflict of interest concerns, all (15) members appointed are from out of state and abroad. [SCRAC] Additionally, the DPH with SCRAC developed collaborative relationships with members of the local, national and international stem cell research community, including scientists, policy makers, advocates and consumers. Overview of Stem Cell Biology Stem cell research is a relatively new area of exploration for scientists, with the potential for significant benefit to human health. This is due to the two unique qualities of stem cells, the ability to develop into different cell types and their capacity for indefinite growth or selfrenewal. Scientists can use these special cells to study the growth and development of tissues and organs, to develop new drugs and to study genetic diseases from the earliest stages. Because their growth can be guided in the laboratory, researchers can push them via a process called differentiation into becoming a specific cell type. For example, a scientist researching spinal cord injury can culture new nerve cells from stem cells. This work has provided many successes in laboratory studies of disease, including diabetes, cardiac disorders, Parkinson s disease, Alzheimer s disease and many more. Although more research is needed to make the jump to consistent successes in humans, many hopes lie in the promise of what may come, including the creation of new tissues and organs, insights into the causes of birth defects and genetic abnormalities, and the development of new drugs. [NIH Stem Cell Basics] Although the term stem cells is often used collectively, there are actually a number of different types of stem cells, each with their own characteristics. Adult stem cells were the first type of stem cells to be explored for clinical use. In an adult, stem cells are present in many tissues and organs, including bone marrow, skin, muscle and fat, in which they produce new, healthy cells to replace those that have been damaged. Bone marrow transplantation is a characteristic example of the use of adult stems cells and remains a therapy that effectively treats many cancer patients each year. Unfortunately, adult stem cells do not have the potential to develop into any cell type, but are restricted to becoming only one or a few specific types of cells. Additionally, they are difficult to maintain and do not multiply indefinitely in culture. A type of stem cell first isolated in humans in 1998, the embryonic stem cell (ESC), is free of these restrictions. These cells are isolated from a blastocyst, or early-stage embryo, can develop into any cell in the body, and can be cultured and expanded in a laboratory indefinitely [Thomson, 1998]. Because of these qualities, ESCs are thought to hold the potential for generating new tissues and organs. Additionally, they are useful as a research tool because seemingly limitless quantities can be obtained from a single blastocyst due to their ability to regenerate. [NIH Stem Cell Basics] 2

21 introduction However, isolating ESCs results in destruction of the fertilized human embryo, which raises ethical issues. Those issues include the moral status of an embryo, and were relevant enough to drive researchers to look for other ways to harness cells with the qualities of ESCs. In 2007, a paper was published that detailed how a human somatic cell (adult skin fibroblast cell) could be reprogrammed to have stem cell qualities namely, limitless renewal and the ability to become any cell type. This new discovery seemingly circumvented the bioethical issues that constrained embryonic stem cell research [Yu, 2007; Yamanaka, 2007]. While researchers agree that induced pluripotent stem cells (ipscs) have an important role in research, the boundaries of their use and limits are far from being known. Like ESCs, these cells can be differentiated into any desired cell type and replicated indefinitely. However, there are important questions that need to be addressed before these cells can be used for clinical therapies, such as do they retain any memory of the original cell and what does the process of creating these cells mean for downstream use, such as implanting them into a patient? There are many expectations and hopes for the potential applications of ESCs and ipcss. Therapeutic applications include use in tissue and organ regeneration, the potential for drug screening and toxicity assessment, and interfaces with gene therapy and tissue engineering. However, funding is still needed for research into the basic biology of stem cells as well as their translation into clinical applications. [NIH Induced Pluripotent Stem Cells] The Political Environment When the CGA established the fund to sponsor stem cell research in 2005, the majority of stem cell researchers in Connecticut were focused on unraveling the potential of ESCs. However, on August 9, 2001, President George W. Bush had introduced a ban on federal funding for research on newly created human embryonic stem cell lines. The policy specified that research on the 71 lines created prior to that date would still be eligible for funding from federal agencies such as the NIH. Unfortunately, only 21 of the stem cell lines proved to be useful for research purposes, leaving many stem cell scientists in an environment where they would not be eligible to receive federal funding for continuing their research [NIH, Stem Cell Policy]. In response, some states including California, New Jersey and Connecticut created their own initiatives to provide funding for stem cell research. In part, these initiatives were intended to keep US scientists and biotechnology firms competitive on an international level. Today, stem cell researchers find the world a very different place. In 2007, the landmark discovery of ips cells was published, and soon after, protocols for creating these cells became accessible to laboratories all over the world. The availability for study of these malleable cells without raising bioethical issues was, and remains, attractive politically, financially and scientifically as they open a new realm of possibilities. The discovery of ips cells has literally opened up a new sub-field of stem cell research for scientists to explore. The political world of 2012 is also changed. In 2009, President Barack Obama repealed the executive order banning federal funding, allowing funding for the use of additional approved stem cell lines [NIH, Stem Cell Policy]. The repeal has helped ESC scientists to access more funding than before, but they face another obstacle. Scientists as a group are facing record lows in federal funding for basic biological research. This is particularly true of the NIH, the organization where stem cell scientists traditionally have looked for research funding. The NIH budget for 2012 and proposed budget for 2013 are $4 billion lower than 2003, the peak year for funding. Also, the number of research project grants funded by NIH has declined every year since

22 introduction Figure 1: Trends in Basic Research by Agency, FY (projected) [AAAS, 2009, FAESB, 2012] Funding incentives for translational and clinical research drive many funding decisions, and for stem cell research, a niche still in its early stages, many researchers are frustrated that basic questions still need to be answered to unlock the use of these cells as a therapeutic tool. 4

23 the connecticut stem cell research program II. THE CONNECTICUT STEM CELL RESEARCH PROGRAM Through 2012, the Connecticut Stem Cell Research Program has awarded 129 grants for a total of $68.8M of the $100M allocated for the program. Five types of proposals have been accepted over the course of the program, each with its own criteria and award amounts: Core Facilities Established Investigators Group Projects, including Disease Directed Collaboration Group Projects (starting in 2011) Hybrid (in 2006 only) Seed All proposals are judged on the same criteria (see 2013 Connecticut Stem Cell Research Program RFP in Appendix A), but consideration is given to the type of grant being applied for as each has distinct goals as stated in the RFP. Table 1 shows information on the number of proposals that were submitted and awarded by institution. For the six RFP processes conducted from , a total of 490 proposals were submitted with 129 (26.3%) being funded. During this period 21 proposals (4.3%) were submitted by companies/organizations other than universities, with one company s proposal being funded in Over this period the average number of proposals submitted per RFP was 81 proposals, with a range of from 70 to 89 proposals; and the average number of proposals funded per RFP was 21.5, with a range of from proposals being funded. For the 2013 RFP currently in process, 109 proposals were submitted for consideration, four or which were submitted by companies. 5

24 the connecticut stem cell research program Table 1: Connecticut Stem Cell Research Program RFP Process: Proposals Submitted/Awarded by Institution ( ) Prop Award Prop Award Prop Award Prop Award Prop Award Prop Award Artificial Cell Tech., Inc. 1 0 CCSU 1 0 Cell Design 1 0 Cheminpharma 2 0 Chondrogenics 1 1 Cognate BioServices 1 0 Connecticut College 1 0 Diagnostic Devices 1 0 Evergen Biotechnologies, Inc. 2 0 Hartford Hospital 1 0 Minerva Tech. 1 0 New Heart, LLC 1 0 Raindance 1 0 Recombinant Tech Triton Thalassic Technologies, Inc. 1 0 UCONN/UCHC Univ. of Hartford WCSU 1 0 Wesleyan Yale Zenith Biotech, LLC 2 0 Subtotal by Year Total Proposals 490 Total Awards 129 Table 2 shows information on the number of proposals submitted and funded by grant type for the six RFP processes conducted from The following provides a summary of the information provided in the table: Core Facilities: 14 proposals were submitted, with 9 being funded Established Investigators: 170 proposals were submitted (with a range from per RFP process) with 50 proposals (29.4%) being funded (with a range of from 7 9 proposals funded per RFP process). For the 2013 RFP process, 39 proposals were submitted for consideration. Group: 21 proposals were submitted (with a range from 1 7 per RFP process), with 4 proposals (19%) being funded (with a range of from 0 2 proposals funded per RFP process). For the 2013 RFP process, 2 proposals were submitted for consideration. 6

25 the connecticut stem cell research program Group - Disease Directed: This grant type was included in the RFP process beginning in For the RFP processes in 2011 and 2012, a total of 5 proposals were submitted with 2 proposals (40%) being funded (with one proposal funded per RFP process). For the 2013 RFP process, 5 proposals were submitted for consideration. Hybrid: This grant type was only included in the RFP process in Four proposals were submitted with 1 proposal (25%) being funded. Seed: 276 proposals were submitted (with a range from per RFP process) with 63 proposals (22.8%) being funded (with a range of from 8 14 proposals funded per RFP process). For the 2013 RFP process, 61 proposals were submitted for consideration. Table 2: Connecticut Stem Cell Research Program RFP Process: Proposals Submitted/Awarded by Grant Type ( ) Grant Type Prop Award Prop Award Prop Award Prop Award Prop Award Prop Award Core Established Group Group - DD Hybrid 4 1 Seed Totals Table 3 shows the number of awards and budget for grants awarded by the program through The table also shows the number of completed grants and actual awards, with many of the awarded grants still in progress. Table 3: Connecticut Stem Cell Research Program Grants Awarded by Grant Type ( ) Connecticut Stem Cell Research Program Grants Awarded by Grant Type Type of Grant Awards Completed Grants # of Grants Budgeted Award # of Grants Actual Award Seed 63 $ 12,564, $ 6,163,710 Established 50 $ 31,860, $ 10,507,606 Group 4 $ 6,565,379 3 $ 5,274,238 Group - DD 2 $ 3,090,499 0 $ - Hybrid 1 $ 3,815,478 1 $ 3,815,478 Core 9 $ 10,950,000 4 $ 7,048,006 Total 129 $ 68,847, $ 32,809,038 7

26 the connecticut stem cell research program Additionally, it is noted that grants that were awarded in 2012 are just in the process of getting started. Therefore, the following provides an overview of the status of the grants awarded through 2011: 110 grants were awarded totaling $59,047, grants, 52% of the total grants awarded, have been completed, totaling $32,809,038 (56%) of the total dollars awarded The number of grants awarded by grant type is shown in Figure 2. Figure 2: Number of Grants Awarded by Grant Type ( ) The amount of funding awarded by grant type is shown in Figure 3. 8

27 the connecticut stem cell research program Figure 3: Amount of Funding Awarded by Grant Type ( ) Each year, SCRAC makes the RFP for the grants available to researchers via the DPH website. Over the course of the program, criteria for some of the grants have been revised. Below is a review of the grant types, the criteria and any major changes that have occurred to the descriptions. This information is presented in Appendix B, RFP Content and Revisions from Seed Grant Awards: These awards are intended to support the early stages of projects that are not yet ready for larger scale funding, whether from federal or non-federal sources. Established investigators new to stem cell research or developing new methodologies, and junior investigators are all eligible for this type of grant. Seed grants may be awarded for a maximum of $200,000 (including indirect costs) and may be expended over two years. Over the course of the program, the criteria for seed grants has not changed significantly; the only the additions have been to encourage junior investigators and those with disease directed research to apply. Established Investigator Awards: These awards are intended for investigators with experience within the stem cell field of research. Awards may be up to (currently) $750,000 (including indirect costs) and may be expended over 4 years. The Established Investigator awards have undergone the most funding changes over the years, with the amount starting at a maximum of $1 million per grant, dropping to $500,000 in 2007, and back to $1million. The funding has been at its current level since

28 the connecticut stem cell research program Group Project Awards: These awards are intended to support coordinated approaches to ambitious strategic goals that are beyond the scope of a typical single laboratory. Two separate types of Group Project Awards are available. Basic group projects can be awarded up to $1.5 million (including indirect costs) and may be budgeted for up to 4 years. The second type of group grant is Disease Directed Collaboration Group Project. Priority is given to projects involving disease directed collaborative arrangements between industry, medical centers and/ or academic institutions, and funding may be may be awarded up to $2 million (including indirect costs) for up to 4 years. These projects should have the intention of beginning Federal Food and Drug Administration review within four years of the awarding of the grant. There have been significant revisions and additions to the criteria of this type of award. In 2007, the funding request allowed decreased to $2 million from $4 million. In 2011, the Disease Directed Group Projects were added as a new type of potential project with a requested funding allowance of a maximum of $2 million for this type of award, while regular Group Project awards were allotted a maximum of $1.5 million. Also, in 2011 a note was added that priority will be given to projects involving disease directed collaboration. Core Facilities Awards: These awards are intended to provide shared core facilities for stem cell researchers at eligible Connecticut institutions, hospitals or companies. Cores operate as service providers both to the institution and beyond, and are allowed to determine fees for service to recover costs. The amount available for funding core facilities in 2013 from the Connecticut Stem Cell Research Program was not to exceed $1 million dollars. The goals and objectives of core facilities include providing expert stem cell materials, analysis, technologies and education to researchers in Connecticut and beyond. In 2007 the amount of funding available decreased from $5 million to $2.5 million, and decreased again in 2012 to $1 million, although that is distributed over the course of 2 years and not 4 years as it was previously. The next most significant changes occurred in 2010 when it was noted that core funding was not a priority in that year. Further, in 2012 the RFP requested a plan for existing core facilities to attain future funding from sources other than the state of Connecticut with such being noted in the budget justification section of the proposal. Hybrid Projects In 2006, hybrid projects were included in the RFP, but this type of project has not been included in the years since. For this project type, applicants were able to propose projects with elements from both Group Projects and Core Facilities. Requested funding for Hybrid Awards was up to a maximum of $5 million (including indirect costs) with funding expended over 4 years. Figure 4 shows the relative amount of funding for each grant type over the course of the Connecticut Stem Cell Research Program thus far. 10

29 the connecticut stem cell research program $7,000,000 Connecticut Stem Cell Research Program Grant Funding by Grant Type ( ) $6,000,000 $5,000,000 $4,000,000 $3,000,000 $2,000,000 $1,000,000 $ (***) Seed $1,984,132 $1,988,676 $2,400,000 $2,799,839 $1,792,086 $1,600,000 Established $5,466,468 $4,046,344 $5,498,216 $6,523,042 $4,926,896 $5,400,000 Group $3,520,000 $1,754,880 $- $- $1,290,499 $- Group - DD $- $- $- $- $1,290,499 $1,800,000 Hybrid $3,815,478 $- $- $- $- $- Core $5,000,000 $2,050,000 $1,900,000 $500,000 $500,000 $1,000,000 Seed Established Group Group - DD Hybrid Core *** Note: The 1st RFP process for the Connecticut Stem Cell Research Program was in It included two years of grant awards totaling $19,786,078, with projects receiving grant awards being under contract in March Figure 4: Connecticut Stem Cell Research Program Grant Funding by Grant Type ( ) GRANT RECIPIENTS Through 2012, all but one of the grants have been awarded to academic institutions. In 2011, Chondrogenics, Inc., a private stem cell company, received a grant award of $1,290,499, with $831,185 being subcontracted to the University of Connecticut Health Center (UCHC). The three academic institutions that have received funding are the University of Connecticut and UCHC, Wesleyan University and Yale University. Funding totals over the first six years of the program are shown in Table 2. It is noted that stem cell research institutional leaders reported Connecticut Stem Cell Research Program funding awarded to their institutions has been a contributing factor in leveraging stem cell research funding from other sources. The universities receiving Connecticut Stem Cell Research Program funding reported total grant awards for the following: total institutional scientific research funding, total stem cell research funding, Connecticut Stem Cell Research Program funding, and stem cell research funding from other sources. Table 4 shows that for this period, Connecticut Stem Cell Research Program funding was 20.8% of total stem cell research funding awarded to these institutions. The table also shows the scale of total stem cell research funding to total scientific research funding, and total Connecticut Stem Cell Research Program Funding to total scientific research funding. 11