Ethics and synthetic gametes

Bioethics

Volumn 19, Issue 2, 2005, Pages 146-166

  Testa, Giuseppe ^a   Harris, John ^b  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BIOENGINEERING; EMBRYONIC STEM CELL; ETHICS; GAMETE; GAMETOGENESIS; GENOME IMPRINTING; HUMAN; LEGAL ASPECT; NONHUMAN; OOCYTE; REVIEW; SPERM;

ANALYTICAL APPROACH; BIOMEDICAL AND BEHAVIORAL RESEARCH; GENETICS AND REPRODUCTION;

ANIMALS; CLONING, ORGANISM; DNA, MITOCHONDRIAL; EMBRYO; EMBRYO RESEARCH; FEMALE; GENETIC ENGINEERING; GENOMIC IMPRINTING; GERM CELLS; HOMOSEXUALITY; HUMANS; MALE; MICE; OOCYTES; REPRODUCTIVE TECHNIQUES, ASSISTED; SAFETY; STEM CELLS;

EID: 17244379935     PISSN: 02699702     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1467-8519.2005.00431.x     Document Type: Review

References (18)

1. th September 2004. 1719.
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3. N. Geijsen, M. Horoschak, K. Kim, J. Grinau, K. Eggan & G.Q. Daley. Derivation of Embryonic Germ Cells and Male Gametes from Embryonic Stem Cells. Nature 2004; 427: 148-154; Y. Toyooka, N. Tsunekawa, R. Akasu & T Noce. Embryonic stem cells can form germ cells in vitro. Proc Nad Acad Sci USA 2003; 100: 11457-11462. K. Hubner, G. Fuhrmann, L.K. Christenson, J. Kehler, R. Reinbold, R. De La Fuente, J. Wood, J.F. Strauss, M. Boiani & H.R Scholer. Derivation of oocytes from mouse embryonic stem cells. Science 2003; 300: 1251-1256.
4. N. Geijsen, M. Horoschak, K. Kim, J. Grinau, K. Eggan & G.Q. Daley. Derivation of Embryonic Germ Cells and Male Gametes from Embryonic Stem Cells. Nature 2004; 427: 148-154; Y. Toyooka, N. Tsunekawa, R. Akasu & T Noce. Embryonic stem cells can form germ cells in vitro. Proc Nad Acad Sci USA 2003; 100: 11457-11462. K. Hubner, G. Fuhrmann, L.K. Christenson, J. Kehler, R. Reinbold, R. De La Fuente, J. Wood, J.F. Strauss, M. Boiani & H.R Scholer. Derivation of oocytes from mouse embryonic stem cells. Science 2003; 300: 1251-1256.
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6. J.A. Thomson, J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall & J.M. Jones. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-1147.
7. That the pluripotent cells isolated from human balstocysts are commonly referred to as human ES cells implies that they are the human counterpart of mES cells. This is however not as straightforward as commonly perceived. The studies of the last few years have indeed confirmed that hES cells share many fundamental features with mES cells, foremost the ability to differentiate in vitro in a wide variety of cell types, and the ability to be cultured in vitro indefinitely without undergoing malignant transformation. But the cornerstone feature to define bona fide ES cells is their ability, when combined with a donor blastocyst, to contribute to all tissues of the ensuing chimera including the germline; since this experiment in humans is ethically untenable, it has been rightly suggested that, in the absence of this fundamental proof, these human cells be more cautiously referred to as human pluripotent stem cells (hPSC), thus underscoring pluripotency as their defining feature while avoiding to assume tout court identity with their murine counterpart (A.G. Smith. Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 2001; 17: 435-462). This is relevant to the theme of this essay, because, lacking the direct in vivo test of hPSC cells' contribution to the germline, it should not be taken for granted that, since synthetic gametes were obtained from mES cells in vitro, the same will be necessarily true also for hPSC. Nonetheless, this could be a matter of technological development, as suggested by the observation that so far, despite intense effort, it has been possible to isolate authentic ES cells (defined through their ability to colonize, after extensive passages of in vitro culture, the germline of the chimeric animal) only from certain strains of mice. This fact offers reasons for both caution and optimism in extrapolating the findings from mES to hES cells. On the one hand it highlights the importance of the genetic background for the ability to establish ES cell lines, and if this is true for different strains of inbred mice, it could potentially be much more relevant to the possibility of therapeutic cloning within the human population, whose genetic heterogeneity might influence the relative success at obtaining customized ES lines from different individual patients. But on the other hand the failure to obtain true ES cells from other species, together with our increased understanding of the differences that exist between the ES cells in vitro and the epiblast from which they were derived, point us to an altogether more contingent interpretation of the data at hand; namely to the suggestion that the ES cell status, rather than being an a priori condition within the embryo epiblast, should be interpreted more correctly as the epigenetic adaptation (with its host of phenotypic consequences) of pluripotent cells within the epiblast to a defined set of culture conditions. And since these culture conditions were first defined for the mouse, it is perhaps not too surprising that their direct application to other species' epiblast cells failed to produce bona fide ES cells. Thus, while a historical look at ES cell research does not enable automatic extrapolations of data across species, it also hints at the possibility that failures reflect more our limited understanding and technical capabilities rather than insurmountable differences among different species.
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11. Hubner et al., op. cit. note 1.
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14. Robert Winston gave the figure of 5 embryos for every live birth some years ago in a personal communication and also gave this figure in a television programme. Anecdotal evidence to me from a number of sources confirms this high figure but the literature is rather more conservative making more probable a figure of three embryos lost for every live birth. See Charles E. Boklage 'Survival Probability of Human Conceptions from Fertilization to Term' in International Journal of Fertility Vol 35. No. 2. 1990: 75-94. Also Henri Leridon Human Fertility: The Basic Components University of Chicago Press, Chicago 1977. Again, in a recent personal communication Henri Leridon confirmed that a figure of three lost embryos for every live birth is a reasonable conservative figure. The point however does not depend upon a precise figure.
15. Robert Winston gave the figure of 5 embryos for every live birth some years ago in a personal communication and also gave this figure in a television programme. Anecdotal evidence to me from a number of sources confirms this high figure but the literature is rather more conservative making more probable a figure of three embryos lost for every live birth. See Charles E. Boklage 'Survival Probability of Human Conceptions from Fertilization to Term' in International Journal of Fertility Vol 35. No. 2. 1990: 75-94. Also Henri Leridon Human Fertility: The Basic Components University of Chicago Press, Chicago 1977. Again, in a recent personal communication Henri Leridon confirmed that a figure of three lost embryos for every live birth is a reasonable conservative figure. The point however does not depend upon a precise figure.
16. J. Burley & J. Harris. 'Human cloning and Child Welfare' in The Journal of Medical Ethics Vol 25. February 1999.
17. John Harris. Wonderwoman & Superman: Ethics & Human Biotechnology. Oxford University Press. Oxford, 1992.
18. John Harris & Søren Holm. 'Extended lifespan and the paradox of precaution' in The Journal of Medicine and Philosophy Vol 27. No. 3. 2002; 355-369.