Stem Cells: Ethical and Regulatory Issues Sidney H Golub, Ph.D Chair, UC Irvine Human Stem Cell Research Oversight Committee (hSCRO) Nobel Laureates 2012 John Gurdon Shinya Yamanaka Stem Cells Make Copies of Themselves Through Cell Division, or … …Stem Cells Adapt for Many Parts of the Body Stem Cells Brain Bone marrow Fat Heart Pancreas Pluripotent Stem Cell Sources • Embryonic Obtained from excess blastocysts from IVF procedures • Fetal Obtained from miscarriages or abortions Some promise shown in treating CNS diseases or injuries • Nuclear transfer to generate blastocysts Same technology for reproductive cloning Unsuccessful thus far in humans • Induced pluripotent stem cells (iPS) created by transferring about genes into adult cells Dominic Doyle Human Blastocyst 0.1-0.2mm diameter Day 4-5 post fertilization Source: NIH website hESC Ethical Issues • Blastocysts as a potential human life • “Respect” for fetal-embryonic materials • Nuclear transfer technology raises the possibility of human reproductive cloning • Research use of human-animal ‘chimeras’ might alter our definition of ‘human’ • Defining the rights of the donors of the genetic material • Equitable use of stem cell products SCNT Current Status • • • • • Theoretical approach to custom design stem cell products and minimize rejection of transplants Wor ks in rodents and large mammals (sheep, dogs) but not yet in humans Claims of SCNT success from South Korea now completely discounted as fraudulent Induced pluripotent stem cells largely supplant SCNT although successful cell fusion with oocyte repor t ed (2011) Restore Homo neander t halensis ? Nobel Prize Winning Experiments Stem Cell to Gamete Nature 491:535-6, 2012 Nature 491:535-6, 2012 Chimeras: Myth or Mad Science? Etruscan chimera statue (Photo: National Geographic) Chimeras are organisms composed of stable combinations of cells derived from different species Chimera Issues • Can human embr y onic stem cells differentiated into brain cells and inser t ed into mouse brain make the mouse think like a human? • Outcome If human stem cells were inser t ed into developing non-human embr y o? • Use non-human oocytes for human SCNT? L Kass “The Wisdom of Repugnance.” • Self-imposed r ules: No breeding of recipient animals, No inter-species blastocysts hESC Ethical Issues • Blastocysts as a potential human life • “Respect” for fetal-embryonic materials • Nuclear transfer technology raises the possibility of human reproductive cloning • Research use of human-animal ‘chimeras’ might alter our definition of ‘human’ • Defining the rights of the donors of the genetic material Views of IVF Patients • • Lyer l y and Faden, Science (2007) 317:46 1244 sur v ey respondents – 1020 with stored embryos • Propor t ion likely to donate for : – infertility research 63% – disease or injury research 62% – stem cell research (derivation) 60% – to infertile couple 22% – thaw and discard 22% • Stem Cell Professional Regulation Guidelines from National Academy of Sciences, ISSCR, other scientific gr oups • Califor n ia and other state standards • Consensus on key points: – Altruistic and consented donations of genetic materials – Provenance of cells and tissues – No reproductive cloning, no reproducing chimeras – Local oversight (SCROs) Current Federal Policy • 1995 NIH appropriation amendment (Dickey-W icker) prohibits federal funding to create or destroy human embr y os for research Renewed annually Legal issues resolved • President G W Bush 2001 limitations on funding lifted by President Obama in 2009 NIH review process: 207 lines eligible for funding, 56 pending (3/2013) • 2005 law promotes umbilical cord blood banking as an alter n ative to ESCs • Fetal cells allowed for transplants (1993) Sale of fetal/embr y onic materials prohibited (2006) Cur r ent Federal Policy Does NOT Affect: • Legality of embr y onic stem cell research • Legality of research using somatic cell nuclear transfer • Authority of states to expand, fund, limit or prohibit stem cell research • Anything to with IVF States with permissive stem cell Legislation or Executive Orders States limiting research (criminal) on embryonic or fetal materials WA MT ME ND OR MN ID WI $ SD WY NV PA UT CO KA AZ OK NM MO IL $ OH IN WV KY MA $ RI CT $ NJ $$ DE MD $ VA NC TN AR SC MS TX MI IA NE CA $$$ NY $$ VT NH AL GA LA AK FL HI 2010 California Proposition 71: “Stem Cell Research and Cures Initiative” • Authorizes $3 billion toward stem cell research (an annual spending limit of $350 million) • Creates "Califor n ia Institute for Regenerative Medicine." • Establishes constitutional right to conduct stem cell research • Prohibits state funding of human reproductive cloning • Passed Nov 2004 with 59% statewide, 52% UCI Human Stem Cell Research Oversight (hSCRO) Committee • Appointed October 2005 • 9-10 members (stem cell science, clinical investigation, fer t ility medicine, ethics, science policy, community reps) • Policy and scientific review About 300 reviews so far, about a third were new 36 ongoing • Coordinates with IRB, IACUC and other oversight bodies UCI hSCRO: Issues Considered To Date • Provenance of cell lines; original consent for donation of materials • Use of pluripotent and differentiated human cell lines in animals • Donation of blastocysts • Donation of oocytes • Parthenogenesis and SCNT • Reprogramming of adult cells The Sue & Bill Gross Stem-Cell Research Center at the University of California, Irvine ... Shinya Yamanaka Stem Cells Make Copies of Themselves Through Cell Division, or … ? ?Stem Cells Adapt for Many Parts of the Body Stem Cells Brain Bone marrow Fat Heart Pancreas Pluripotent Stem Cell Sources... Embryonic Stem Cells from Somatic Cell Nuclear Transfer (SCNT) If inner cell mass is placed in culture, the stem cells will divide Develops into a blastocyst Asexual production of pluripotent stem cells. .. organisms composed of stable combinations of cells derived from different species Chimera Issues • Can human embr y onic stem cells differentiated into brain cells and inser t ed into mouse brain make