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Stem Cell Battles Are Far From Over

By Michael Cook

Induced pluripotent stem cells are not the ethical breakthrough they were initially thought to be.

In November 2007 a Japanese team led by Shinya Yamanaka of Kyoto University announced that ordinary human skin cells could be reprogrammed to make them pluripotent. He called them induced pluripotent stem (iPS) cells.

The news transformed stem cell biology. Within weeks, leading scientists like James Thompson of the University of Wisconsin, who had first isolated human embryonic stem (hES) cells, and Ian Wilmut, who had created Dolly the cloned sheep, changed tack. They dropped hES cells and began working on the dazzling new cells.

A significant motivation was the ethical and political difficulties. In 2001 US President George W. Bush restricted the amount of federal funding available for hES cell work because he had qualms about working with cells derived from the destruction of human embryos. While Australian politicians were not quite so scrupulous, they also recognised the political sensitivity of hES cell research and wrapped it in red tape.

Politicians and religious groups were not the only ones with ethical misgivings. Yamanaka himself told the New York Times about the first time he viewed a human embryo under a microscope. “When I saw the embryo, I suddenly realised there was such a small difference between it and my daughters. I thought: we can’t keep destroying embryos for our research. There must be another way.”

Does this mean that iPS cells carry no ethical baggage? Certainly that is the impression given by many foes of embryo research, but this is misleading. Even iPS cell research has ethical complications.

First, there are the ethical issues associated with any new therapy. At the moment iPS cells are far from safe. Yamanaka’s cells could have caused cancer. “Right now we are a long way from being sophisticated enough to take advantage of these cells’ potential,” neuroscientist Arnold Kriegstein of the University of California, San Francisco, told Nature recently. “Things are still at a very early stage.”

Second, the malleability of iPS cells means that they could be used for controversial purposes. Already some research teams are trying to create sperm and eggs from iPS cells. This would make it possible for gay couples to have children that are genetically their own.

Some progress has been made towards this headline-grabbing goal. Last year scientists at M.D. Anderson Cancer Center in Houston produced male and female mice from two fathers using iPS cells. The technique is too complicated to be practical but the potential for ethical controversy is enormous.

Third, as a bioethicist at Case Western Reserve University in Cleveland, Insoo Hyun, pointed out in Clinical Pharmacology and Therapeutics, a Nature journal, research on iPS cells is “inexorably intertwined” with research on hES cells. Most stem cell scientists regard hES cells as the “gold standard” for pluripotency. They argue that research must proceed along parallel tracks because iPS cells have to be compared with hES cells to guarantee that they are functionally equivalent.

“Thus, if one believes that embryo destruction for hES cell derivation is a wrongful act (as a sizable minority of Americans believes it is), then all iPS cell researchers and other downstream users would be materially and formally complicitous,” Hyun wrote.

If this is the case, drug companies will be obliged to attach ethical warnings to iPS cell-derived products for patients who might object. Some clinicians would pose problems of conscientious objection. The complications are endless.

Another issue is justice in distributing the financial benefits from iPS cells. If a drug is developed from iPS cells derived from a patient biopsy, does he or she have a right to remuneration?

When iPS cells burst into the media, nearly all newspapers described them as an ethical breakthrough because they had apparently made therapeutic cloning and hES cell research obsolete overnight. The reality is far more complex. Ethical and political issues will crop up as long as researchers persist in two-track research towards their dream of pluripotency.

Michael Cook is editor of the online bioethics newsletter BioEdge.