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Transforming Stem Cells into Sperm Cells Yields Unexpected Bioethical Questions

Researchers at Newcastle University in England have pushed cell reprogramming into uncharted bioethical territory, claiming to have transformed stem cells into human sperm. Reports in the British press from last week indicated that the work is intended as a treatment for male infertility, but the possibility of generating gametes from other adult cells raises a host of questions about how humans might go about making babies in the future.

Current British law prohibits using the cells for reproductive purposes, and even after the years it may take to improve on the technique, serious safety questions about using them to fertilize a human egg would remain. Some biologists are also questioning whether what the team led by Professor Karim Nayernia have generated are really functional sperm, and others have yet to reproduce the experimental results. But none of this changes the fact that the moment to confront the implications of stem cell research for assisted reproduction is upon us. SP Editor-in-Chief Jonathan Moreno tackled this issue in Science Next, pointing out that conservatives who pushed induced pluripotent cells and reprogramming as alternatives to embryonic stem cells didn’t stop to think about the impact the work could have on procreation. As Moreno points out, coaxing stem cells into sperm may be the first step, but similar techniques might be able to turn stem cells into blastomeres, rendering every cell in the body a potential embryo. The analysis is worth quoting at length:

But scientists and bioethicists alike will have to confront the new possibilities for artificial human reproduction inherent in the rapidly advancing stem-cell biology. Already a British group has reported that it has coaxed human female embryonic stem cells to develop into cells with some of the essential qualities of sperm. Suppose one were to pursue an attempt to transform a diploid cell (a body cell with all forty-six chromosomes) into a haploid gamete (a sperm or egg cell with only twenty-three chromosomes). This might involve first expelling half the genetic complement (as has apparently already been done in mouse cells), and then treating the remainder with factors that are required for gametic processes.

It seems that opponents of embryonic stem-cell research who celebrated the advent of iPS cells have not grasped that the cellular reprogramming technique actually aggravates their greatest concerns about the power of modern biology. For if skin cells can be reprogrammed to become pluripotent and then differentiated into specific somatic cell types, they may also be differentiated into germ (sex) cells.

Since male iPS cells have both X and Y chromosomes, they could be reprogrammed to sperm and eggs. These iPS-derived sperm and eggs could then be used in standard in vitro fertilization procedures. Notably, couples with an infertile male partner may be able to obtain sperm that could then be transferred to the woman’s uterus. The resulting infant would have virtually the full complement of DNA of both members of the couple, though whether the male can be called the father in the traditional biological sense will be a matter of debate. Alternatively, it may be possible for a gay male couple to obtain an oocyte derived from the skin cell of one member of the couple, which could then be combined with the sperm from the second man and the embryo brought to term through the services of a gestational or surrogate mother. The resulting child would be genetically related to both men. Lacking a Y chromosome, a lesbian couple would not be able to reproduce in this way. However, if the genes sort differently during the formation of each of the gametes, there would be grave risks for any resulting embryo. It should not be necessary to elaborate on the extraordinary ethical and social questions that would be raised by such developments. In an overview of the issues raised by pluripotent stem cells, the Hinxton Group, an international consortium on stem-cell ethics and law, urged caution in any new regulatory regime that might be stimulated by these questions: “In the case of PSC-derived gametes, as with all science, it is important to target policy specifically to those dimensions of the research or its applications that have proved to be unacceptable, and that these policies be proportionate to the magnitude of what is morally at stake.”

But that is not the end of the story. If iPS-derived germ cells are in the offing, then so are blastomeres, the cells that constitute an embryo at its very earliest stages. To turn a diploid cell into a blastomere one might either use the induced germ cell in a process of parthenogenesis or spermatogenesis, or introduce factors that skip the gamete stage and turn the iPS cell directly into a blastomere. Thus will come to pass the most astonishing and disorienting result of all: modern stem-cell biology will at that point have made every cell of our body a potential embryo.

All of these scenarios tread the dangerous territory between science and science fiction. The genetic resorting that would take place through several steps of reprogramming from adult cells to iPS cells to gametic cells would almost surely make it too dangerous to attempt human reproduction, so as in the case of reproductive cloning, issues of risk would have to be dealt with before more profound ethical issues would need to be addressed. Yet how many stem-cell biologists, including Thomson and Yamanaka, predicted that reprogramming would be accomplished so quickly?

A more plausible scenario for the use of iPS cells to produce a genetic twin of the cell donor has already been demonstrated in mice by scientists at Advanced Cell Technology, a Worcester, Massachusetts, biotech company. “We now have a working technology whereby anyone, young or old, fertile or infertile, straight or gay can pass on their genes to a child by using just a few skin cells,” a company official said. Moreover, the official added, “the bizarre thing is that the Catholic Church and other traditional stem-cell opponents think this technology is great when in reality it could in the end become one of their biggest nightmares. . . . It is quite possible that the real legacy of this whole new programming technology is that it will be introducing the era of designer babies.”

Widespread appreciation of this technical reality could have profound effects on the divisive abortion debate, but in what directions? There seem to be at least several distinct possibilities, all of which may co-exist. The first and most likely short-term possibility is that prolife groups will split between those that wish to ban such procedures as antithetical to the natural process of conception and those that find it an acceptable alternative along the lines of in vitro fertilization. A second, more extreme, result and far less likely result would be that the human embryo in its early, disorganized state prior to, say, the appearance of the primitive streak (roughly around fourteen days) comes to be seen as no more than another clump of cells. Eventually, something like the traditional view still reflected in Islam, Judaism, and most Protestant denominations may once again be accepted even by those who once held a more elevated view of the early embryo. A third possible outcome of the advent of iPS-derived embryos, and one that is perhaps the most distant, is that a growing proportion of the public comes to view the tissues and organs that compose the human body as the remarkable systems they are, rich with life and the potential for independent life. Cults that worship every cell and even every sloughed cell can be imagined.

What is clear is that our society is unprepared for breakthroughs in the life sciences that we can foresee just over the horizon. For some, the new dawn of mastery over our own biology that will follow from the technology of induced pluripotency will seem like a cruel joke and confirm their worst fears. Some may even be reminded of the myth of Prometheus, whose punishment for stealing fire from the gods and sharing it with humans was to be tethered to a rock where his liver was consumed by an eagle. Thus we may conclude that, though humans may suffer for their knowledge, neither will it consume them, for the liver happens to be the only organ in the human body capable of complete regeneration, a definitive property of pluripotent cells.

(Jonathan Moreno, from “Stem Cells and the Betting of Moral Milestones” in Science Next)

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