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Cash or a Prayer Book

New Hurdles for Adult Stem Cell Research

SOURCE: James Thomson, University of Wisconsin Induced pluripotent stem cells.

Not too long ago I was opining in these pages about the omnipresence of hype in the debate over research involving embryonic stem cells. One of the areas I listed among my most-hyped examples was the love affair that critics of publicly funded embryonic stem cell research have with induced pluripotent stem cells, or iPSCs.

Induced pluripotent stem cells are artificially derived from adult cells. The adult cell is tricked into expressing specific genes that are present but latent. iPSCs have until recently been generated from adult nonreproductive cells by expressing four different genes called transcription factors.

The creation of iPSCs was first reported in 2006 by a Japanese team led by Shinya Yamanaka. Many groups have since reported the ability to generate these cells using some variations involving the same four transcription factors. These techniques allow adult cells to behave like embryonic cells—cells capable of being turned into nearly any type of cell. Colleagues of mine at the University of Pennsylvania just recently reported a simpler, safer way to achieve much more efficient adult cell transformation into iPSCs.

Conservatives who abhor embryo destruction have been the greatest proponents of iPSC research as an alternative to using cells from human embryos. Conservative columnist Charles Krauthammer has long gushed that iPSCs make the debate over public funding of embryonic stem cell research moot.

Back in 2007, right after the announcement was made that researchers in Japan had discovered how to reprogram adult skin cells to resemble embryonic stem cells, Krauthammer declared that President George W. Bush had been prescient in banning public funds for embryonic stem cell research. (Hey, I thought President Bush and his defenders claimed then and continue to aver now that what they had in mind was a “compromise,” not a ban. But hey, ban, compromise, whatever, I guess). Krauthammer maintained that since there was a way to create “a magical stem cell that can become bone or brain or heart or liver” without using human embryos, any argument for using stem cells derived from any type of human embryo made no scientific sense.

Krauthammer has had a loud chorus echoing his devotion to the magic of iPSCs. Everyone from William Hurlburt, former member of President Bush’s Bioethics Council, to a host of prolife groups and evangelical publications has been espousing the idea that there was no reason to talk any longer about funding research with stem cells obtained by destroying human embryos.

But the case for iPSCs as the alternative to using embryos has now, as I warned it would, come under fire.

A team led by Yang Xu, professor of molecular biology at the University of California, San Diego, has just reported in the journal Nature that iPSCs trigger severe immune reactions when implanted into mice. In some cases the cells were completely destroyed by the animals’ immune systems.

Although the studies were done in rodents, the findings raise doubts over the future use of iPSCs in humans. Xu said at a press conference that “the assumption that cells derived from iPS cells are totally immune-tolerant has to be reevaluated before considering human trials.” In English he is saying that somehow, in turning adult cells into embryonic-like iPSCs, the immune system sees them as foreign tissue and kills them. This is not a good thing if you are using these modified cells to try and cure diseases.

So what is the take-home message from all of this? Well, iPSCs may still have a future but it is likely to prove rocky. So will research involving embryonic stem cells. So will work using cells derived from cloned human embryos. Even adult stem cells are going to have a few bad days. In the early days of research in a new area, no one can say with any certainty what will work or that anything will work. Research is difficult and often fails. Asking today which form of stem cells are likely to have the most benefit in curing humans is akin to asking the Wright brothers whether they thought interplanetary exploration ought be done by humans or robots.

Making research decisions based on pronouncements by those with huge ethical or ideological stakes in the game—in the case of iPSCs, those opposed to the destruction or manipulation of human embryos—makes for very poor science policy. When people with strong faith commitments about the sanctity of human embryos argue that “science” shows that one type of research eliminates the need for another, watch out! When it comes to science, conflicts of interest can come in the form of cash or a prayer book.

Arthur Caplan, Ph.D., is the Director of the Center for Bioethics and the Sidney D. Caplan Professor of Bioethics at the University of Pennsylvania.

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