The ethics of stem cell research and treatment Bernard Lo, M.D. March 12, 2009 1
hesc: ethical controversies Moral status of embryo? Clearly a potential person Some believe a person with rights Is hesc derivation morally acceptable? If embryo a person, deriving hesc line tantamount to murder 5
Pro-life support for stem cell research from Sen Hatch This research is consistent with bedrock pro-life, pro-family values. Stem cell research facilitates life; abortion destroys life. 8
Pro-life support for stem cell research from Sen Hatch I cannot equate... abortion... with the simple act of disposing of a frozen embryo that will never complete the journey toward birth. 9
2001 U.S. policy for hes cells Federal NIH funding permitted for research using existing hesc cell lines No funding to use other lines No funding to derive new hesc lines 10
2001 U.S. policy for hes cells Federal funding permitted for Adult, cord blood stem cells ips cells 11
Proposition 71 Established right to carry out research with pluripotent stem cells Including SCNT for research Priority to research that may not be funded by NIH May not pay donors of materials beyond expenses 13
2009 Executive Order Allow federal funding for hesc research using frozen embryos that Otherwise be destroyed or remain frozen 14
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Stem cell lines with specific DNA Models for studying disease in lab Identify new targets for therapies Test effectiveness of candidate drugs For stem cell therapy Autologous Allogeneic 16
Induced pluripotent stem cells (ips cells)
Beta cells for transplantation Islet cell transplantation Differentiation of hesc cells Differentiation of ips cells No immune rejection Direct nuclear reprogramming of pancreatic exocrine cells 19
A new era in stem cell research? ips cells do not involve embryos President s Council on Bioethics Ethically unproblematic and acceptable for use in humans 20
Are new hesc lines still needed? Concerns about cancer Oncogenes Insertional mutagenesis from retrovirus vectors 21
Donor concerns about basic research Genetic modification of cells Large-scale genome sequencing Injection of cells into animals Patenting of discoveries Sharing with other researchers 22
Donor concerns about basic research Common research techniques Other types of stem cells Other kinds in research Usually not discussed with donors Some donors would object 23
San Francisco Chronicle UCSF researcher injected human neural cells into mouse brains Never told me, donor says Ethics committee approved study 24
Donor concerns about downstream research Transplantation into other persons Reproductive research Other studies that cannot anticipate 25
Resolving informed consent challenges May not violate preferences of donors Need to explain stem cell research 26
Resolving informed consent challenges Use only donors who agree to Basic stem cell research Genetic sequencing and manipulation Injection into animals Patenting Sharing with other researchers Be recontacted in future 27
Resolving informed consent challenges Additional specific consent for sensitive downstream research Autologous transplantation Reproductive research 28
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Rationale for stem cell transplantation Shortage of donors for Islet cell transplantation Transplant beta cells Derived from stem cells Direct reprogramming of pancreatic exocrine cells 30
Ethical issues in any clinical trial 1. Risk / benefit balance Outcomes are uncertain Participants at risk, but not designed to benefit them IRB must approve 31
Stem cell risks Pluripotent Differentiate into unintended cells Integrate into unintended targets Multicentric tumors In vitro manipulation Reprogramming do awry 32
Particular concerns about risk Long-term adverse effects in chronic illness Hard to discontinue intervention 33
Stem cell risks Pluripotent Differentiate into unintended cells Integrate into unintended targets Multicentric tumors In vitro manipulation Reprogramming do awry 34
Stem cell transplants in Parkinson Embryonic dopaminergic neurons Transplanted cells Localized to target areas Grew Produced dopamine NEJM 2001;344:710 35
Stem cell transplants worsened Parkinson No improvement in clinical outcomes Late disabling dyskinesia and dystonia in 15% Continued despite adjustment in medication Believed due to excess of dopamine NEJM 2001;344:710 36
What is different about SC clinical trials? Limited experience in humans Hope, expectations 37
Ethical issues in any clinical trial 2. Informed consent Therapeutic misconception IRB tend to require longer consent forms 38
Stem cell barriers to consent Strong scientific plausibility Limited experience in humans Hope, expectations 39
Improving the consent process Assess comprehension of key features of trial Clinical Trials 2008; 5: 517-522 40
Key features of stem cell trials Different than clinical care Not sure that intervention effective or safe May have serious side effects May be unexpected Cannot reverse the intervention 41
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Selection of participants In Phase 1 trial Children May be more effective early in disease Most to lose if severe adverse events Cannot give informed consent to accept risk Adults 43
Selection of participants In pivotal Phase 3 trial Children Most to gain if effective and safe Adults 44
Recommendations for clinical trials 1. Coordinated scientific and ethical review If science flawed, risks not acceptable Review by IRB, FDA problematic IRB should evaluate scientific merit 45
Recommendations for clinical trials 2. Enhanced informed consent IRBs emphasize consent forms Therapeutic misconception Administer questionnaire to test comprehension 46
Recommendations for clinical trials 2. Enhanced informed consent State if cell-based therapies from hescs 47
Recommendations for clinical trials 3. Publish findings even if negative 48
Summary Stem cell research progressing rapidly Ethics and policy need to keep pace with science Implications for other types of research 49
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