Eggs and Sperm from Stem Cells on the Horizon, Ethics Group Tells AAAS Meeting

Ruth Faden

Scientists may be able to grow eggs and sperm, in part or in whole, from multipurpose stem cells within five to 15 years, an international study group has concluded. It says that oversight structures must be in place before there are any attempts to use such cells for treatment of infertility or other clinical applications.

Those applications could be many years away, if at all. But the Hinxton Group—an international consortium of scientists and ethicists—says it is not too early to grapple with some of the challenging ethical and policy questions that arise from efforts to create gametes (sperm and eggs) in the laboratory from so-called pluripotent stem cells, or cells with the capacity to develop into all the different cells in the human body.

The group released a consensus statement on the implications of the research at a news briefing in the United Kingdom on 14 April. Members of the group's steering committee discussed the statement at a 15 April meeting at AAAS. The Hinxton group was organized in 2006 to anticipate challenging issues surrounding stem cell research and develop guidance for ensuring scientifically and ethically defensible research.

Pluripotent stem cells have been isolated from various sources, including early-stage human embryos and adult human cells that have been coaxed to revert to an embryonic state. During the past five years, studies with mice have shown that cells resembling eggs and sperm can be grown in the lab from embryonic stem cells. Human pluripotent stem cells also have been shown to give rise in the lab to cells with characteristics of the earliest stages of germ cells, the progenitors of sperm and eggs.

Such work is currently providing significant insights in basic research. In addition, it may help fertility researchers better understand how reproductive cells mature and could open the door to new forms of assisted conception. But the work also raises controversial possibilities, such as that a baby might one day be conceived from two laboratory-grown stem cells, one manipulated to become a sperm and the other an egg.

Ruth Faden, executive director of the Berman Institute of Bioethics at Johns Hopkins University and a member of the Hinxton Group, said there are ethical and social issues surrounding both the basic research now underway and the potential clinical applications down the road.

The only way to confirm that laboratory-created sperm or eggs are functional, Faden said, is to use them in the creation of embryos. The Hinxton Group "wanted to squarely acknowledge," she said, the need to create embryos, maintain them to the blastocyst stage (about 100 cells) and then destroy them as an intrinsic part of the research effort. "There's no way to get around that step," Faden said.

If the lab-grown gametes do prove to be functional, researchers should be able to make scientific advances by studying those cells alone rather than embryos, the Hinxton Group said. Such research could include exploring the role of specific genes in germ cell development, the origin of chromosomal abnormalities and the development of fertility treatments for people with disease or injury of the ovaries or testes. If the research eventually does produce functional human gametes, it could reduce the need to obtain eggs from women (and the hyper-stimulation of the ovaries such collection requires) for research or fertility treatments, Faden said.

The Hinxton Group's consensus statement dismissed as highly improbable one possibility that has drawn considerable attention in the popular press: that sperm could be produced from a woman's stem cells or eggs from a man's, thereby allowing lesbian or gay couples to have babies for whom both partners contribute an equal genetic component.

"It is likely to be very difficult to derive eggs that could be used for reproduction from XY (chromosomally male) cells," the statement says. "There are biological and technical reasons that will make it even more difficult, or even impossible, to derive sperm that could be used for reproduction from XX (chromosomally female) cells." The female cells contain no Y chromosome, which contains genes needed for sperm production.

Robin Lovell-Badge

Robin Lovell-Badge, head of the division of stem cell biology and developmental genetics at the National Institute for Medical Research in London, said the group concluded that it "would be very difficult or practically impossible" for same-sex couples to create their own biological children using gametes derived in the lab.

Lovell-Badge said it will be difficult enough to grow stem cell-derived gametes in the laboratory that are functional and safe for possible use in applications such as fertility treatments. The natural process by which a sperm cell or egg cell is created in the testes or ovaries is incredibly complex. To replicate it in a test tube "is a major challenge," he said.

But there is a large potential payoff in understanding basic mechanisms in the growth and development of gametes. "If you can study some of this in vitro," Lovell-Badge said, "then we could gain lots of information that would be relevant to human biology," whatever the eventual utility of the cells for clinical applications.

Debra Mathews

The Hinxton Group said it is important to protect the rights and interests of those providing cells for study and manipulation. In particular, any individual who contributes tissue must give specific consent for those tissues to be used for reproductive purposes, said Hinxton member Debra Mathews, assistant director for science programs at Hopkins' Berman Institute.

The group noted that societies have the authority to regulate science, and scientists have a responsibility to obey the law. But while urging strict research protections, the consensus statement also asked policymakers to "refrain from interfering with scientific inquiry unless there is a substantial justification for doing so that reaches beyond disagreements based solely on divergent moral convictions." It adds: "Any interference with scientific inquiry should be derived from reasonable concerns about demonstrable risks of harm to persons, societal institutions, or society as a whole."

Faden said that the research on stem cell-derived gametes shouldn't be prevented or restricted just because there are contentious moral disagreements about the possible outcomes of the work. Society should do what she called "the hard work to reach sufficient consensus" about the road forward, based on "defensible and public reasons."

The 15 April meeting was sponsored by AAAS, the Johns Hopkins Berman Institute of Bioethics, and the British Embassy, and was held at AAAS headquarters in Washington, D.C.

Earl Lane

23 April 2008