Independent Citizens Oversight Committee Scientific Staff California Institute for Regenerative Medicine December 9, 2013 Dear Members

of the Independent Citizens Oversight Committee and CIRM Scientific Staff: We are writing as Directors, Managers, and users of CIRM-funded Shared Research Laboratories and Training Courses to urge continuing support of the successful programs, which are vital to current and future CIRM-funded efforts. We understand that CIRM appointed an external Scientific Advisory Board (SAB) in July 2013, which recommended CIRM discontinue its Shared Laboratory program. The SAB enthusiastically supported continuation of the training courses but not the Shared Laboratory infrastructure that supports them. Six of the 17 centers are combined CIRM Research and Teaching Laboratories; the Shared Laboratories are the places where the training takes place. The Research laboratories also provide hands-on training to collaborators. The reality is that the training programs will have to be cancelled if the laboratories are not supported. The original mission of the Shared Laboratories was motivated by concern about NIH funding limitations: "to create dedicated laboratory space for the culture and maintenance of hESCs, in particular the hESC lines that fall outside the federal guidelines, by supporting the creation of core laboratories to be used by multiple investigators conducting research in the home institution and neighboring research institutions." The principal argument for the SAB's recommendation is that the NIH has expanded their registry of human embryonic stem cells to 234 lines; this is interpreted as making the CIRMfunded labs redundant for supporting hESC research that could be funded by the NIH. In fact, many of the Shared Laboratories support research with novel hESC lines, including lines derived from single blastomeres, early-stage embryos, or parthenotes. These lines are not approved by the NIH because they do not meet the Federal definition of being derived from a blastocyst-stage human embryo. The CIRM-funded infrastructure has helped bring California researchers NIH funding that explicitly requires an existing stem cell facility. California researchers have been able to successfully compete for NIH funding because they have access to established stem cell facilities. The NIH has not stepped up to fill the void in funding of dedicated centers for human pluripotent stem cell research and this situation is not expected to improve over the next few years, as the NIH is decreasing its support of infrastructure programs. The Shared Labs have provided much needed equipment for a growing number of stem cell researchers, and have been able to support experienced research and training staff. As these grants begin to expire in the next year, the loss of support for staff salaries and supplies will decimate the Shared Laboratories. There is no alternative place for this research to take place. 1

In the worst case scenario, the loss of indirect cost support to the institutions will mean that the core lab space will be reallocated (a certainty for many independent research institutes), effectively dismantling the Shared Laboratories and putting CIRM equipment into storage. Shared Laboratory personnel provide support not only for the millions of dollars of CIRMpurchased equipment, but often also the additional equipment that has been funded by other sources as a result of the CIRM infrastructure investment. Even in the best cases, there will be no means to support the staff and maintain the equipment. Some institutions may be able to provide space without indirect costs, but will not fund personnel and equipment maintenance. Thus, the original CIRM investment in infrastructure will be lost, and CIRMs highly successful training programs for new workers (CIRM Bridges and Training Grants), will be left without homes. CIRMs clinically oriented awards depend on the Shared Labs and Training Centers. Development of protocols for generation of clinically needed cell types will not be possible without the Shared Lab infrastructure. As the clinical projects are expanding, their need for the Shared Laboratory resources increases. The Shared Laboratories have become the signature program that distinguishes the CIRM philosophy from that of other granting agencies. Over the years, the Shared Laboratories have taken on much more extensive missions than were initially envisioned and have become the heart of stem cell research efforts in California. They are the places where researchers learn technologies, share ideas, and plan collaborations. Each of the Shared Labs has developed its own character and role. Shared Laboratories are used for far more than research on non-NIH approved hESCs. They are used as training centers for Bridges trainees and for researchers from around the world; for quality-controlled generation of iPSCs; as well-maintained, pathogen-free cell culture labs; as centers for sophisticated equipment, with trained personnel for guidance; and for outreach to the community, through tours and high school internships. The media know that they can consult Shared Lab directors for accurate, understandable information about stem cells. We realize that CIRM is motivated to shift focus and funding toward clinical projects. Therefore, we urge you to consider establishing a funding mechanism that will support the ongoing efforts of successful Shared Laboratories and Training centers. We believe that given the discretionary power of CIRM's scientific program directors, a solution can be found to continue in this new context necessary support for Shared Laboratories that are used for Training Programs and for infrastructure for vital CIRM projects, including clinical projects. In summary: CIRM's Shared Laboratory and Training Centers Have evolved far beyond their original mission as havens for hESC research. Are now primary centers of innovation and collaboration that leverage the stem cell expertise of multiple scientists. Have launched a new generation of creative scientists, who are filling the need for highly trained stem cell researchers in California and the rest of the world.

Are training a cadre of young scientists who will be essential for providing technical support for the growing stem cell biotech industry. Have become crucial hubs for developing stem cell therapies for a multitude of diseases. Are raising the level of understanding of the value of stem cells among the greater community of taxpayers, lawmakers, and policy makers. Are still the only places where research with nonfederal stem cell lines can be done.

We urge you to retain the value of CIRM's investment by supporting our highly trained professional staff, providing infrastructure support, and continuing to provide training for scientists who will carry on CIRM's mission into the future. Sincerely, Peter Donovan, Ph.D. Professor, Department of Developmental and Cell Biology U.C. Irvine School of Biological Sciences University of California Irvine, CA pdonovan@uci.edu Susan Fisher, Ph.D. Professor, Ob/Gyn & Reproductive Sciences Faculty Director, Biomolecular Resource Center University of California San Francisco, CA sfisher@cgl.ucsf.edu Jeanne F. Loring, Ph.D. Professor, Department of Chemical Physiology Director, Center for Regenerative Medicine The Scripps Research Institute La Jolla, CA jloring@scripps.edu W. Travis Berggren, Ph.D. Director Stem Cell Core Salk Institute for Biological Studies La Jolla, CA tberggren@salk.edu Dennis Clegg, Ph.D. Professor and Co-Director Center for Stem Cell Biology and Engineering Department of Molecular, Cellular and Developmental Biology University of California Santa Barbara, CA

clegg@lifesci.ucsb.edu Victoria Fox, Ph.D. Director - USC Stem Cell Core Facility Program Director - USC EiHS Summer Program in Stem Cell Research Assistant Professor of Research Medicine Eli and Edythe Broad Center for Regenerative Medicine Los Angeles, California, victorif@usc.edu Linda C. Giudice, M.D., Ph.D., M.Sc. Distinguished Professor and Chair Department of Obstetrics, Gynecology & Reproductive Sciences The Robert B Jaffe MD Endowed Professor in the Reproductive Sciences University of California San Francisco giudice@obgyn.ucsf.edu Lindsay Hinck, Ph.D. Professor MCD Biology University of California Santa Cruz, CA lhinck@ucsc.edu Kathryn N. Ivey, Ph.D. Staff Research Investigator Stem Cell Core Director Gladstone Institutes San Francisco, CA kivey@gladstone.ucsf.edu Leslie Lock, Ph.D. Director of Educational and Research Outreach Sue and Bill Gross Stem Cell Research Center University of California Irvine, CA llock@uci.edu Andrew P. McMahon, Ph.D. Director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research Provost Professor and W. M. Keck Professor of Stem Cell Biology and Regenerative Medicine Chair, Department of Stem Cell Biology and Regenerative Medicine University of Southern California Los Angeles, CA amcmahon@med.usc.edu

Renee A Reijo Pera, Ph.D. Professor Director, Stanford University Doctoral Program in Stem Cell Biology & Regenerative Medicine Institute for Stem Cell Biology & Regenerative Medicine Department of Obstetrics and Gynecology Stanford University School of Medicine Lorry Lokey Stem Cell Building Stanford, CA reneer@stanford.edu Suzanne Peterson, Ph.D. Staff Scientist Manager, CIRM Shared Laboratory and Training Center Center for Regenerative Medicine The Scripps Research Institute La Jolla, CA David Schaffer, Ph.D. Professor, Department of Bioengineering and Chemical Engineering Co-Director, Berkeley Stem Cell Center University of California Berkeley, CA schaffer@berkeley.edu Evan Snyder, M.D., Ph.D. Professor Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research Director, Stem Cells and Regenerative Biology Program La Jolla, CA esnyder@sanfordburnham.org Alice F. Tarantal, PhD Professor, Departments of Pediatrics and Cell Biology and Human Anatomy, School of Medicine Associate Director, UC Davis Stem Cell Program Director, Translational Human Embryonic Stem Cell Shared Research Facility Stem Cell Shared Research Facility University of California Davis, CA aftarantal@primate.ucdavis.edu Prue Talbot, Ph.D. Professor of Cell Biology Director, UCR Stem Cell Center and Stem Cell Core Facility College of Natural and Agricultural Sciences Cell Biology & Neuroscience University of California at Riverside Riverside, CA prue.talbot@ucr.edu 5

Inder Verma, Ph.D. Irwin and Joan Jacobs Chair in Exemplary Life Science American Cancer Society Professor of Molecular Biology The Salk Institute Laboratory of Genetics La Jolla, CA verma@salk.edu David Warburton, OBE, DSc, MD, MMM, FRCP, FRCS, FRCPCH Professor of Pediatrics, Surgery and Craniofacial Biology Director, Developmental Biology and Regenerative Medicine Program Director, CIRM Training Program and Shared Laboratory Saban Research Institute Childrens Hospital Los Angeles Los Angeles, CA DWarburton@chla.usc.edu Xianmin Zeng, Ph.D. Associate Professor Director North Bay CIRM Shared Research Laboratory for Stem Cells and Aging Buck Institute for Age Research Novato, CA xzeng@buckinstitute.org