Let's Be Clear About the Science and Ethics of iPS Cell Research and Its Reproductive Possibilities


1 Winston L. Duke, "The new biology", in Reason, Magazine, "Parahuman Reproduction, Android Cloning, The New Biology, Artificial Synthesis, Genetic Engineering Brain Transfers" (August 1972), pp. 4-11; see analysis by Dianne N. Irving, "Historic roots of human genetic engineering: Reason, Duke, and parahuman reproduction (1972)", July 11, 2004, at: http://www.lifeissues.net/writers/irvi/irvi_34winstonduke.html. [Back]

2 UNESCO, Report of the Eighteenth Session of the International Bioethics Committee (31 May - 2 June 2011), Baku, Azerbaijan; Human Cloning and International Governance (June 2, 2011), at: http://www.unesco.org/new/fileadmin/MULTIMEDIA/HQ/SHS/pdf/Human-Cloning_IBC18_2011.pdf. [Back]

3 Ibid. [Back]

4 Kathy A. Fackelmann, "Researchers 'clone' human embryos" (October 30, 1993), Sci News.;144(18):276, at: http://findarticles.com/p/articles/mi_m1200/is_n18_v144/ai_14289947/; also at PubMed: http://www.ncbi.nlm.nih.gov/pubmed/11659660. [Back]

5 Ibid. [Back]

6 Ibid. [Back]

7 Kathy A. Fackelmann, "University probe faults 'cloning' research; George Washington University board concludes approval for research was attained without full disclosure of facts" (December 17, 1994), Sci News;146(25):406, at: http://findarticles.com/p/articles/mi_m1200/is_n25_v146/ai_16027235/; also at: http://www.ncbi.nlm.nih.gov/pubmed/11659894. [Back]

8 James A. Thomson, Joseph Itskovitz-Eldor, Sander S. Shapiro, Michelle A. Waknitz, Jennifer J. Swiergiel, Vivienne S. Marshall and Jeffrey M. Jones, "Embryonic Stem Cell Lines Derived from Human Blastocysts" (November 6, 1998), Science, Vol. 282 no. 5391 pp. 1145-1147; doi: 10.1126/science.282.5391.1145; at: http://www.sciencemag.org/content/282/5391/1145.full [Back]

9 James A. Thomson, Yu, J. et al., "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells", Science (2007), 318, 1917-1920; at: http://www.sciencemag.org/content/318/5858/1917.abstract. [Back]

10 John D. Gearhart, Michael Shamblott et al, "Derivation of pluripotent stem cells from cultured human primordial germ cells" (November 10, 1998), Proc Natl Acad Sci USA, 95(23):13726-13731; PMCID:PMC24887, at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC24887/. [Back]

11 Kazutoshi Takahashi1 and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors" (August 25, 2006), Cell, Volume 126, Issue 4, 663-676, doi:10.1016/j.cell.2006.07.024, at: http://www.cell.com/retrieve/pii/S0092867406009767. [Back]

12 Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors" (November 30, 2007), Cell, Volume 131, Issue 5, 861-872, doi:10.1016/j.cell.2007.11.019; at: http://www.cell.com/abstract/S0092-8674(07)01471-7. [Back]

13 "Genetic Abnormalities Identified in Pluripotent Stem Cell Lines" (January 6, 2011), UC San Diego Health System News, at: http://health.ucsd.edu/news/2011/Pages/01-06-genetic-abnormalities.aspx. See also, Louise Laurent, Igor Ulitsky, Ileana Slavin, Ha Tran et al, "Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and iPSCs during Reprogramming and Time in Culture" (January 7, 2011), Cell Stem Cell, Volume 8, Issue 1, 106-118, at: http://health.ucsd.edu/news/2011/Pages/01-06-genetic-abnormalities.aspx. [Back]

14 Rebecca Robey, "Stem cell setback: Reprogrammed stem cells may induce immune response", BioNews (May 23, 2011), at: http://articles.latimes.com/2011/feb/03/health/la-he-stem-cells-20110203. [Back]

15 "Some stem cells hold on to their past, researchers say" (February 3, 2011), Los Angeles Times, at: http://articles.latimes.com/2011/feb/03/health/la-he-stem-cells-20110203. See also: Charles Q. Choi, "Cell-Off: Induced Pluripotent Stem Cells Fall Short of Potential Found in Embryonic Version" (February 11, 2010, Scientific American, at: http://www.scientificamerican.com/article.cfm?id=cell-induced-pluripotent. [Back]

16 Zhao T, Zhang ZN, Rong Z, Xu Y, "Immunogenicity of induced pluripotent stem cells", Nature, May 13, 2011; 474(7350):212-5. doi: 10.1038/nature10135; at: http://www.ncbi.nlm.nih.gov/pubmed/21572395. [Back]

17 Bradley J. Fikes, "Stem cell and regenerative medicine's future: Video from Ian Wilmut's speech" (December 5, 2011), North County Times, at: http://www.nctimes.com/blogsnew/business/scitech/stem-cell-and-regenerative-medicine-s-future-video-from-ian/article_6f87eb38-3405-5ffd-9fec-d565555e1eba.html. [Back]

18 Lee ST, Chu K, Jung KH, Song YM, Jeon D, Kim SU, Kim M, Lee SK, Roh JK., "Direct generation of neurosphere-like cells from human dermal fibroblasts" (July 13, 2011), PLoS One:6(7):e21801, PMID 21765916; at: http://www.ncbi.nlm.nih.gov/pubmed?term=%22direct%20reprograming%22. [Back]

19 "Tetraploid complementation", at: http://stemcells.nih.gov/info/glossary.asp. [Back]

20 A Nagy, J Rossant, R Nagy, W Abramow-Newerly, and J C Roder, "Derivation of completely cell culture-derived mice from early-passage embryonic stem cells" (September 15, 1993), PNAS vol. 90 no. 18 8424-8428, at: http://www.pnas.org/content/90/18/8424.abstract?ijkey=6ab68791138142043b37cf616d8709d6c886b026&keytype2=tf_ipsecsha. [Back]

21 Patrick P. L. Tam and Janet Rossant, "Mouse embryonic chimeras: tools for studying mammalian development" (December 22, 2003), Development 130, 6155-6163; doi: 10.1242/dev.00893; at: http://dev.biologists.org/content/130/25/6155.full. [Back]

22 Lan Kang, Jianle Wang, Yu Zhang, Zhaohui Kou, Shaorong Gao. 2009. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell, doi 10.1016/j.stem 2009.07.001, PMID 19631602, at: http://www.ncbi.nlm.nih.gov/pubmed?term=19631602. [Back]

23 Xiao-yang Zhao, Wei Li, Zhuo Lv, Lei Liu et al, "iPS cells produce viable mice through tetraploid complementation" (September 3, 2009) Nature 461, 86-90, doi:10.1038/nature08267; Published online 23 July 2009, at: http://www.nature.com/nature/journal/v461/n7260/abs/nature08267.html. [Back]

24 Ronald Naumann, "Production Of Tetraploid Mouse Embryos By Electrofusion", Biocompare: The Buyer's Guide for Life Scientists, (as of November 2, 2011); at: http://www.biocompare.com/Articles/ApplicationNote/1642/Production-Of-Tetraploid-Mouse-Embryos-By-Electrofusion.html. [Back]

25 Roger Bertolotti, "Fully pluripotent iPS cells: Mouse tetraploid complementation, ethical human ES-like cells and reproductive cloning ban", World Scientific Journals (June 19, 2010), Volume: 6, Issue: 1(2011) pp. 21-32; doi 10.1142/S1568558610000148, at: http://www.worldscinet.com/gtr/06/0601/S1568558610000148.html. [Back]

26 Denker, H. W., "Induced pluripotent stem cells: how to deal with the developmental potential", Reprod Biomed Online. 2009;19 Suppl 1:34-7, at: http://www.ncbi.nlm.nih.gov/pubmed/19622249. [Back]

27 Shi V. Liu, Ke-Ming Cui and Wei-Kang Zhang, "Why Do We Need "Fully Pluripotent" iPS Cells?" (August 19, 2009), Top Watch 4(2):29-30, at: http://im1.biz/albums/userpics/10001/TW2009V4N2A2_iPS_full.pdf. [Back]

28 Shi V. Liu, Ke-Ming Cui and Wei-Kang Zhang, "iPS Mice: Passing Acid Test Or Breaking Basic Ethics?" (August 11, 2009), Top Watch 4(2):27-28, at: http://im1.biz/albums/userpics/10001/TW2009V4N2A1_iPS_mice.pdf. [Back]

29 Ibid. [Back]

30 Ibid. [Back]

31 Man Tong, Zhuo Lv, Lei Liu, Hui Zhu, Qin-Yuan Zheng, Xiao-Yang Zhao, Wei Li, Yi-Bo Wu, Hai-Jiang Zhang, Hua-Jun Wu, Zhi-Kun Li, Fanyi Zeng, Liu Wang, Xiu-Jie Wang, Jia-Hao Sha and Qi Zhou, "Mice generated from tetraploid complementation competent iPS cells show similar developmental features as those from ES cells but are prone to tumorigenesis", Cell Research, (August 30, 2011), doi:10.1038/cr.2011.143, at: http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2011143a.html. [Back]

32 Shi-Lung Lin, "Concise Review: Deciphering the Mechanism Behind Induced Pluripotent Stem Cell Generation" (October 25, 2011), Stem Cells, 2011;29:1645-1649, doi: 10.1002/stem.744, at: http://onlinelibrary.wiley.com/doi/10.1002/stem.744/abstract. [Back]

33 David Cyranoski, "Mice made from induced stem cells; Technical feat shows that the different route to stem cells can indeed make a full mammal body", Nature 460, 560 (July 23, 2009), doi:10.1038/460560a, at: http://www.nature.com/news/2009/090723/full/460560a.htm; see also; Xiao-yang Zhao, Wei Li, Zhuo Lv, Lei Liu, Man Tong1, Tang Hai, Jie Hao, Chang-long Guo, Qing-wen Ma, Liu Wang, Fanyi Zeng & Qi Zhou, "iPS cells produce viable mice through tetraploid complementation", Nature 461, 86-90 (September 3, 2009), doi:10.1038/nature0826, at: http://www.nature.com/nature/journal/v461/n7260/abs/nature08267.html. [Back]

34 Lo B, Parham L, Alvarez-Buylla A, Cedars M, Conklin B, Fisher S, Gates E, Giudice L, Halme DG, Hershon W, Kriegstein A, Kwok PY, Wagner R., "Cloning mice and men: prohibiting the use of iPS cells for human reproductive cloning", Cell Stem Cell. (January 8, 2010); 6(1):16-20, at: http://www.ncbi.nlm.nih.gov/pubmed/20085739. [Back]

35 Andrew Pollack, "Stem cells: Tissue rejection blurs treatment hopes", New York Times (May 14, 2011(, at: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2011/05/13/MNRH1JG69R.DTL. [Back]

36 The Hinxton Group: An International Consortium on Stem Cells, Ethics and Law (as of Nov. 3, 2011); "The Science, Ethics and Policy Challenges of Pluripotent Stem Cell-Derived Gametes (PSCDG)"; Listing of references on the science, ethics and same sex topics; Note this list of references ranges only from 2000 - 2008; the field has exploded since then; at: http://www.hinxtongroup.org/au_pscdg_refs.html.

LIST: SCIENCE; PSCDG Review Articles: Aflatoonian B, Moore H., "Germ cells from mouse and human embryonic stem cells", Reproduction 2006; 132(5):699-707; Clark AT, Reijo Pera RA., "Modeling human germ cell development with embryonic stem cells", Regen Med 2006; 1(1):85-93; Daley GQ., "Gametes from embryonic stem cells: a cup half empty or half full?", Science 2007; 316(5823):409-410; Kehler J, Hubner K, Garrett S, Scholer HR, "Generating oocytes and sperm from embryonic stem cells", Semin Reprod Med 2005; 23(3):222-233; Nagano, MC, "In vitro gamete derivation from pluripotent stem cells: progress and perspective", Biol Reprod 2007; 76(4):546-551; PSCDG Articles: Clark AT, Bodnar MS, Fox M et al, "Spontaneous differentiation of germ cells from human embryonic stem cells in vitro", Hum Mol Genet 2004; 13(7):727-739; Drusenheimer N, Wulf G, Nolte J et al, "Putative human male germ cells from bone marrow stem cells", Soc Reprod Fertil Suppl 2007; 63:69-76; Dyce PW, Wen L, Li J., "In vitro germline potential of stem cells derived from fetal porcine skin", Nat Cell Biol 2006; 8(4):384-390; Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, Daley GQ., "Derivation of embryonic germ cells and male gametes from embryonic stem cells", Nature 2004; 427(6970):148-154; Hubner K, Fuhrmann G, Christenson LK et al, "Derivation of oocytes from mouse embryonic stem cells", Science 2003; 300(5623):1251-1256; Kerkis A, Fonseca SA, Serafim RC et al, "In vitro differentiation of male mouse embryonic stem cells into both presumptive sperm cells and oocytes", Cloning Stem Cells 2007; 9(4):535-548; Lacham-Kaplan O, Chy H, Trounson A., "Testicular cell conditioned medium supports differentiation of embryonic stem cells into ovarian structures containing oocytes", Stem Cells 2006; 24(2):266-273; Nayernia K, Li M, Jaroszynski L et al, "Stem cell based therapeutical approach of male infertility by teratocarcinoma derived germ cells", Hum Mol Genet 2004; 13(14):1451-1460; Nayernia K, Nolte J, Michelmann HW et al, "In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice", Dev Cell 2006; 11(1):125-132; Nayernia K, Lee JH, Drusenheimer N et al, "Derivation of male germ cells from bone marrow stem cells", Lab Invest 2006; 86(7):654-663; Toyooka Y, Tsunekawa N, Akasu R, Noce T., "Embryonic stem cells can form germ cells in vitro", Proc Natl Acad Sci USA 2003; 100(20):11457-11462; iPS Cells: Nakagawa M, Koyanagi M, Tanabe K et al, "Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts", Nat Biotechnol 2008; 26(1):101-106; Park IH, Zhao R, West JA et al, "Reprogramming of human somatic cells to pluripotency with defined factors", Nature 2008; 451(7175):141-146; Takahashi K, Yamanaka S., "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell 2006; 126(4):663-676. Other Science Articles: McLaren A., "Primordial germ cells in the mouse", Dev Biol 2003; 262(1):1-15; Hunt PA, Hassold TJ, "Human female meiosis: what makes a good egg go bad?", Trends Genet 2008; 24(2):86-93; Kono T, Obata Y, Wu Q et al, "Birth of parthenogenetic mice that can develop to adulthood", Nature 2004; 428(6985):860-864; Lawrence LT, Moley KH, "Epigenetics and assisted reproductive technologies: human imprinting syndromes", Semin Reprod Med 2008; 26(2):143-152; Smith KR., "Gene Therapy: The Potential Applicability of Gene Transfer Technology to the Human Germline", Int J Med Sci 2004; 1(2):76-91; Yates F, Daley GQ, "Progress and prospects: gene transfer into embryonic stem cells", Gene Ther 2006; 13(20):1431-1439; van de Lavoir MC, Diamond JH, Leighton PA et al, "Germline transmission of genetically modified primordial germ cells", Nature 2006; 441(7094):766-769; Kazuki Y, Hoshiya H, Kai Y et al, "Correction of a genetic defect in multipotent germline stem cells using a human artificial chromosome", Gene Ther 2008; Hohenstein KA, Pyle AD, Chern JY, Lock LF, Donovan PJ, "Nucleofection Mediates High-efficiency Stable Gene Knockdown and Transgene Expression in Human Embryonic Stem Cells", Stem Cells 2008.

ETHICS: Ethics of PSCDG: Testa G, Harris J, "Ethics and synthetic gametes", Bioethics 2005; 19(2):146-166; Lippman A, Newman SA, Testa G, Harris J., "The Ethics of Deriving Gametes from ES Cells", Science 2005; 307(5709):515c-517c; Master Z., "Embryonic stem-cell gametes: the new frontier in human reproduction", Hum Reprod 2006; 21(4):857-863; McLaren A., "Free-range eggs?", Science 2007; 316(5823):339; Mertes H, Pennings G., "Embryonic stem cell-derived gametes and genetic parenthood: a problematic relationship", Cambridge Quarterly of Healthcare Ethics 2008; 17:7-14; Newson AJ, Smajdor AC., "Artificial gametes: new paths to parenthood?", J Med Ethics 2005; 31(3):184-186; Testa G, Harris J., "Genetics. Ethical aspects of ES cell-derived gametes", Science 2004; 305(5691):1719; Whittaker P., "Stem cells to gametes: how far should we go?", Hum Fertil (Camb ) 2007; 10(1):1-5.

SAME SEX PARENTS: Greenfeld DA., "Gay male couples and assisted reproduction: should we assist?", Fertil Steril 2007; 88(1):18-20; Maccallum F, Golombok S., "Children raised in fatherless families from infancy: a follow-up of children of lesbian and single heterosexual mothers at early adolescence", J Child Psychol Psychiatry 2004; 45(8):1407-1419; Tasker F., "Lesbian mothers, gay fathers, and their children: a review", J Dev Behav Pediatr 2005; 26(3):224-240. Other Ethics Articles: Sade RM., "Introduction: religions and cultures of East and west: perspectives on bioethics", J Law Med Ethics 2008; 36(1):7-9; Chan S, Harris J., "The ethics of gene therapy", Curr Opin Mol Ther 2006; 8(5):377-383; Harris J., "Essays on science and society: Intimations of immortality", Science 2000; 288(5463):59; Kass LR., "L'Chaim and its limits: why not immortality?", First Things 2001;(113):17-24; Kimmelman J., "The ethics of human gene transfer", Nat Rev Genet 2008; 9(3):239-244; Mehlman MJ., "Genetic enhancement: plan now to act later", Kennedy Inst Ethics J 2005; 15(1):77-82; Mwase IM, "Genetic enhancement and the fate of the worse off", Kennedy Inst Ethics J 2005; 15(1):83-89; Savulescu J., "Education and debate: Deaf lesbians, 'designer disability,' and the future of medicine", BMJ 2002; 325(7367):771-773. [Back]

37 J. Burley, in Ariff Bongso and Eng Hin Lee, Stem Cells: From Bench to Bedside (London: World Scientific Publishing Company), 2 edition, November 4, 2010; pp. 669-670. [Back]

38 Ibid. [Back]

39 Roger Highfield, "Sperm cells created from female embryo" (January 31, 2008), The Telegraph (UK), at: http://www.telegraph.co.uk/science/science-news/3323846/Sperm-cells-created-from-female-embryo.html. [Back]

40 Marques-Mari, Lacham-Kaplan, Medranol, Pellicer, and Simon, "Differentiation of germ cells and gametes from stem cells" (January 28, 2009), Hum. Reprod. Update (2009) doi: 10.1093/humupd/dmp001, at: http://humupd.oxfordjournals.org/content/early/2009/01/28/humupd.dmp001.full. [Back]

41 Ibid. [Back]

42 Park, TS., Galic, Z., Lindgren, A., Conway, AE., Van Handel, BJ., Magnusson, M., Richter, L., Teitell, MA., Mikkola, HKA., Lowry, WE., Plath, K., Clark, AT, "Derivation of Primordial germ cells from Human embryonic and induced pluripotent stem Cells is significantly improved by co-culture with human fetal gonadal cells" (April 2009), Stem Cells 27(4):783-95; PMID: 19350678; at: http://www.ncbi.nlm.nih.gov/pubmed/19350678; see also Gkountela, S., Lindgren, A. and Clark, AT. "Pluripotent stem cells in reproductive medicine: Formation of the human germ line in vitro", In Stem Cells and Regenerative Medicine From Molecular Embryology to Tissue Engineering, ed. Appasani, K & Appasani, RK, Humana Press, 2010 Page 371; at: http://www.mcdb.ucla.edu/Research/Clark/publications.html; quoted in Lauren Gravitz, "Grow Your Own Eggs and Sperm" (February 2, 2009), Technology Review (MIT), at: http://www.technologyreview.com/printer_friendly_article.aspx?id=22042. [Back]

43 Neri QV, Takeuchi T, Rosenwaks Z, Palermo GD, "Treatment options for impaired spermatogenesis: germ cell transplantation and stem-cell based therapy" (August 2009), Minerva Ginecol. 61(4):253-9, PMID: 19745793; at: http://www.ncbi.nlm.nih.gov/pubmed/19745793. [Back]

44 Said Assou, John de Vos, Samir Hamamah, "Generation of artificial gametes from human pluripotent stem cells: Is this possible?" (Jan. - March 2011), MT / médecine de la reproduction, gynécologie et endocrinologie. [Medicine of reproduction, gynecologie and endoctrinology] Volume 13, Number 1, 11-9, janvier-mars 2011, Mini-revues, at: http://www.jle.com/en/revues/medecine/mtg/e-docs/00/04/66/61/resume.phtml. [Back]

45 "Keio approves plan to create sperm, ova using iPS cells" (February 10, 2011), Daily Yomiuri Online, at: http://www.yomiuri.co.jp/dy/features/science/T110209004225.htm. [Back]

46 Yao L, Yu X, Hui N, Liu S., "Application of iPS in assisted reproductive technology: sperm from somatic cells?" (September 2011), Stem Cell Rev. 7(3):714-21, PMID: 21318596, at: http://www.ncbi.nlm.nih.gov/pubmed/21318596. [Back]

47 Brigid O'Connell, "Woman may one day make their own sperm from skin cells" (November 6, 2011), Herald Sun, at: http://www.heraldsun.com.au/news/more-news/woman-may-one-day-make-their-own-sperm-from-skin-cells/story-fn7x8me2-1226186635220. [Back]

1, 2, 3,