The puzzling, versatile nature of pluripotent stem cells recalls ancient debates confronting the Christian Church.
Technological advances have long influenced discussion of nonscientific issues, so it stands to reason that biology informs the religious concept of personhood. In 1869, a fuller understanding of the biology of fertilization prompted Pope Pius IX to adopt the Roman Catholic Church's current doctrine that a developing human embryo gains a soul when sperm joins egg1. Previously, the Church held the traditional stance that “ensoulment” occurred at quickening, or 40 days after conception. Ironically, the Pontiff was actually ahead of the game with this pronouncement; it was not until 1876 that Oskar Hertwig showed conclusively that the sperm actually enters the egg at fertilization.
Today, many Jewish and Islamic theologians keep the 40th day after conception as the critical cut-off, and most research guidelines prohibit growing human embryos past 14 days, the onset of organogenesis. Even so, the papal ruling that human life begins at conception underlies much of the ethical debate surrounding embryonic stem (ES) cell research in many Western countries. However, recent studies on stem cells could have as profound an effect on our thinking as studies in fertilization had on our 19th-century counterparts.
Ten years ago, the birth of Dolly the sheep put the molecular mechanisms underlying somatic cell reprogramming within reach2, creating a mammal that came from the union of two cells, but not the union of sperm and egg. Other efforts led to the creation of all sorts of paradoxically flexible cells: ES cells with genomes taken from terminally differentiated cells and hybrid somatic-ES cell lines. Just this year, genetically modified skin cells have been transformed into embryonic-like stem cells that contributed to both sperm and eggs in chimeric animals. In other words, somatic cells were induced into a state of pluripotency.
Germline cells can also be induced to give rise to pluripotent cells in vitro. Shinohara Kanatsu reported that ES-like cells can be generated from cultures of spermatogonial stem cells taken from the testes of neonatal mice3, and this was confirmed by Guan et al. using similar cells from adult testis4.
Cells in the early embryo naturally give rise to all manner of somatic cells, and most scientists believe they will eventually be able to steer ES cells down any of myriad pathways, assuming they find the right conditions. Several groups have also shown that ES cells in culture are able to give rise to various germline cells. Clearly, ES cells and their pluripotent ES-like equivalents occupy a central position as the nexus of all cell lines. Just as both germline and soma can be transformed into pluripotent stem cells, so can pluripotent cells differentiate into germline and somatic cells. The map of potential pathways is still incomplete, but at this point filling in the terra incognita is only a matter of time. Already, the interconnectivity is evident, and as it becomes more widely recognized, it seems bound to trigger new ways of thinking about very old questions.
The dual nature of pluripotency
The interconnectivity of reprogramming and differentiation pathways recalls ancient debates on duality and the divine. For many Japanese, raised in a secular culture with spiritual roots in Buddhism and Shintoism, the distinctions between the three major branches of Western monotheism are somewhat obscure. But we do see that only Christianity has a tradition of using human figures in its iconography, which makes Roman Catholic churches with their stained glass, statuary, and other human imagery feel more intimate to us. As with Eastern religions, there is no contradiction depicting God as human. In fact, we have the dual nature of Christ as both god and human to thank for the grand tradition of Christian religious art in the West.
Perhaps ES cells will be able to propagate beyond the culture dish and into culture itself.
Modern biotechnology is now tackling issues that confronted the church fathers over a thousand years ago as they developed what was to become the Roman Catholic dogma of Marianism, which held that Mary is theotokos (“mother or bearer of god”). In 431 AD, at the third ecumenical council in Ephesus, a debate raged on how the creator could be born to the created: the paradox was ultimately resolved by acknowledging Jesus' divine and human natures. This is the same fundamental paradox that we now face in modern studies of pluripotency and reprogramming.
In a sense, both biotechnology and the early Church engaged in a struggle against nature6. Investigators are now seeking to push the boundaries of what can give rise to, and what can arise from, pluripotent cells—efforts that may require a re-evaluation of the definition of pluripotency itself7. Before these dreams of reprogramming cell fate and limitless self-renewal were realized in the culture dish, the conceptual taxonomy was more clear-cut: germ cells represented a sort of transcendent continuity (allowing an individual's genes to survive beyond the individual), and soma represented mortality and transience.
The induction and differentiation of pluripotent stem cells in culture links these two lineages, which are kept strictly segregated in the natural body. In 431 AD, the ecumenical council was vexed and inspired by Christ's dichotomous nature, a dangerous idea that blurs the distinction between god and human. Today, ES cells and their pluripotent ilk present similar dualities: their propensity for eternal life is both essential (reproductive and reparative) and diabolical (cancerous). They can come from natural and artificial sources and represent both germline and soma. Indeed, once functional gametes can be generated from pluripotent stem cells, endless generations of cells could be bred in vitro. Given the methods currently available for manipulating cells in vitro, one cell line could be another cell line's genetic sibling, cousin, or great-grandsire.
In short, the boundaries are no longer distinct between germline and soma, between differentiation and pluripotency. It is difficult to say whether these modern dualities will spark new philosophies or artistic conventions, as the theotokos concept so richly did, but perhaps ES cells will be able to propagate beyond the culture dish and into culture itself.
Kiessling, A.A. & Anderson, S. Human Embryonic Stem Cell: An Introduction to the Science and Therapeutic Potential. Bartlett and Jones Publisher Inc. (2003).
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).
Campbell, K.H. et al. Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64–66 (1996).
Kanatsu-Shinohara, M. et al. Generation of pluripotent stem cells from neonatal mouse testis. Cell 119, 1001–1012 (2004).
Guan, K. et al. Nature Pluripotency of spermatogonial stem cells from adult mouse testis. 440, 1199–1203 (2006).
Serres, M. Hominescence. Le Pommier (French) (2001).
Niwa, H. How is pluripotency determined and maintained? Development 134, 635–646 (2007).
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Nishikawa, S., Sipp, D. Dualities of Christ and stem cells. Nat Rep Stem Cells (2007). https://doi.org/10.1038/stemcells.2007.76