Presentation on theme: "Class 12 ethical issues related to stem cells"— Presentation transcript:
1 Class 12 ethical issues related to stem cells What are stem cells?adult, lineage-specific (e.g. bone marrow-blood)embryonal, pluri-(or toti-)-potentWhat is differentiation?Where do embryonal stem cells (ESC) come from?blastocyst, inner cell mass,~ day 5, before implantationin vitro fertilization (IVF)
2 Other sources of stem cells Fetal germ cell (sperm, egg) precursorsSomatic cell nuclear transfer (SCNT) ->enucleated egg (cloning)Induced, pluripotent stem cells (iPSC)somatic (non-germ cell) cells, e.g. skin cellstimulated to de-differentiate usingDNA or RNA or proteins involvedin controlling differentiation
3 What are potential uses of stem cells? reproductive cloningcell therapy to replace damaged tissuese.g. after heart attack, spinal corddamage, Parkinson’sIF you can control differentiationhow well can we control differentiation?are these likelihoods exaggerated?iPSC are most impressive example,but be skeptical…
4 What kinds of evidence suggest that some cells are pluripotent or totipotent?In vitro, or in animal (in vivo) expression ofproteins typical of 3 “primary” developmentaltissues (endo-, ecto-, meso-derm)Chimeras – mix black strain mouse ESC with whitemouse strain embryo -> implant in utero -> puphas black/white coat (some cells from each setof parents); note DNA does NOT mix - cells keep their genetic identity. Breed chimeric pup with black mouse; if sperm/egg from chimera has“black” genotype, you get pure black strain offspring; this proves ESC were totipotent
5 What are ethical dilemmas? hESC come from embryos (or germinal ridgeof aborted fetuses)Should a 5-day embryo be considered a human?When does life begin in a moral sense?Is it problematic to set a criterion, e.g. gamete fusion,implantation, formation of primitive streak, abilityto feel, to think? Are these arbitrary, do theydistinguish us from animals, are they too late?
6 Suppose you could treat gametes in way that precluded their developmentinto embryo or fetus, but allowedthem to form hESC…would this avoid the ethical problem?or is it a “gimmick” that relies on arbitrarinessof “when life begins” definition?is it different from just deciding not to implantfertilized eggs?
7 Do many, even those with fairly absolutist views, implicitly recognize an intermediate status?e.g., those opposed to abortion except in caseof rape; the fetus is not guilty, so rape does notjustify its abortion; suggests the holder of this view views the fetus as not equivalent to a childGiven lack of agreement, and strength of views,should governments seek a middle position,e.g. no taxpayer money for hESC researchbut allow it to be done privately?
8 What would Kant say?What is a Utilitarian view?What are views of different religious groups?Who’s interests are denied if you don’t allowgovernment funding of stem cell research?Alta Charro’s view: don’t focus on unanswerablequestions but on balancing political rights:the more intense the views of those opposedand the more limited their political options, thegreater the likelihood of medical progress mustbe to justify government funding; => don’t hype
9 In vitro fertilization quandaries Multiple embryos usually created at oncebecause of medical risks of collecting eggs? impracticality of freezing-thawing eggsNon-implanted embryos are frozenWhat to do with unused embryos?Donate to another couple?Keep frozen indefinitely?Discard?Use for research?
10 If used for research, is this “using” a human being? Should it be the parents’ decision?If the sperm comes from an anonymous donor,should the mother be able to donote w/ofather’s consent?Should the issue of donation be discussed onlyafter a decision to destroy the embryo, toavoid biasing toward research use?Should IVF physician and researcher be differentpeople to avoid conflict of interest?
11 Should it be illegal to pay for donation, to avoid financial inducement?Should the parent(s) have the right to limituse of resulting stem cells, e.g. foruse of family members?Should parent(s) have the right to withdrawuse of stem cells at some future date?Is it ok to create embryos by in vitro fertilizationexpressly for research, i.e. not asby-products of reproduction?
12 Should government funding for research use of hESC be more tightly regulated thanprivate funding?Should there be limits to how long human embryoscan be cultured in vitro – e.g. stop beforedevelopment of primitive streak?Should reproductive cloning be illegal? Why?Should there be restrictions on mixing hESC withother species’ blastocysts and implantingin animal uteri to see how the hESC cellsdevelop? Will animal studies like this be necess-ary for FDA approval of therapeutic hESC lines?
13 Bush era policy:I. No federal funding for research that involvesdestroying an embryo (Dickey-Wicker amend.)II. Federal funds can be used to study hESClines that were already in existenceIs II unethical if you accept I? Is this analagous to:surgeons who transplant murder victims’ organsdon’t condone murder; what if the donors wereprisoners executed for capital crimes?Only ~ 20 hESC lines were in existence at that time,and many were patented. Is this a problem?
14 2005 - National Academy of Science (NAS) Guidelines To provide guidelines for private sector and stategovernment funded hESC researchOK to create hESC for research aloneprovided fully informed, un-coerced consent,no monetary payment or other inducements,All parents must consent – so can’t useembryos with anonymous sperm donorOK to inject hESC into animals but no progenyanimals can be bred out of concern that humangerm cells might be produced
15 NAS Guidelines – cont’d Must set-up local ESC Research OversightCommittees - like IRBs - because someresearch involving hESCs escapesIRB review (hESCs are not consideredhuman subjects)No reproductive cloningNo injecting ESCs into human uteriNo injecting hESCs into non-human primate uteriNot legally binding
16 2009 - Obama relaxes some Bush restrictions Allow federally funded research on new hESClines (derived without federal funds)All hESC used in federal research must haverigorously obtained parental consentStill no federal funding for creation of hESC(as this involves destroying embryos)No funding for SCNT experiments
17 Obama ironies –Some Bush era hESC lines did not haveadequate consent documentation - solist of approved cell lines went down!2010 – DC District Court Judge declared all NIHresearch on hESC illegal, on theory that itviolates prohibition on destroying embryos(Dickey-Wicker amendment, passed everyyear since 1996 by foes of hESC research)
18 Do you agree with the District judge that you shouldn’t be able to use federal fundsto study objects you can’t use federalfunds to create?Even it Congress was fully aware of theethical compromise and supported it?The Appeals Court ruled the NIH can continueto fund hESC research while the DistrictCourt’s decision is appealed
19 iPSCs – is this a way out of ethical quandaries? iPSC = pluripotent stem cells from somatic cellsso no need to destroy an embryoMajor scientific advance in terms of control ofdifferentiation stateFirst done by injecting 4 cancer-causing/transcription regulatory genes; butinjecting DNA -> mutation; eventuallyrepeated by transient exposureto small # of proteins
20 But controversies:Do iPSCs have same broad differentiationpotential as hESCs?iPSCs appear to have more mutations,epigenetic changes than hESCsWhat are cancer risks assoc. with stem-celltherapies, given close connectionbetween de-differentiation and cancer?
21 Main pointsTechnology challenges old ways of makingdistinctions in complex moral problemsTough to balance differing views whenfundamental issues of life andreproduction are involvedhESC are derived from ~5 day old embryos;they can differentiate into lots of tissues;they have promise (so far unrealized) forcell therapy of several diseases
22 US government has taken intermediate position allowing federal funding for researchuse but not creation of hESC lines,provided parents give informed consentThis compromise has had Republican andDemocratic support, but is being challengedin court; challenge could be “mooted”if Congress abolished Dickey-WickerPrivate sector is freer to develop hESC; thiswork is subject to voluntary regulation