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Issue Date:  January 11, 2008

Advances don't quell stem-cell debate

Kansas City, Mo.

If headlines turn out to be prophetic, Nov. 20, 2007, was a historic day in the decade-long ethical debate over embryonic stem-cell research. “Scientists Bypass Need for Embryo to Get Stem Cells,” reads The New York Times. “Major leap for stem cells,” the Chicago Tribune added. “Advance May End Stem Cell Debate,” chimed The Washington Post.

But headline prophecies are a tricky business and less than two months later, it appears The Washington Post was wise to use the word, “may.”

-- Kyodo News

Shinya Yamanaka

-- GettyImages/AFP/
Jeff Miller

James A. Thomson

On Nov. 20, the Tuesday before Thanksgiving, Shinya Yamanaka of the University of Kyoto, Japan, and James A. Thomson of the University of Wisconsin both published papers from separate experiments with similar results: by inserting four key genes, they were able to reprogram adult human skin cells into acting like embryonic stem cells. Those reprogrammed stem cells could someday be grown into any kind of human tissue and offer potential cures to major diseases. All this without extracting the cells from human embryos, a method that draws fire from pro-life activists who believe life begins when an egg is fertilized.

But the debate is not over yet.

The news certainly had the chairman of the Committee for Pro-Life Activities at the U.S. Conference of Catholic Bishops ready to sing certain scientists’ praises.

“Studies published this week in the journals Cell and Science offer new hope for advancing stem-cell research and therapies while fully respecting the dignity of human life,” wrote Cardinal Justin Rigali of Philadelphia.

Such conclusions go too far, according to William B. Neaves, president and CEO of the Stowers Institute for Medical Research in Kansas City, Mo. “These are important advances toward the ultimate goal of being able to directly reprogram human cells,” said Neaves. “But by no means do these advances mean that one should cut back in any way on the effort devoted to research with human embryonic stem cells.”

Few question the potential good that stem-cell technologies represent. By being able to create new tissue, stem-cell therapy could someday cure a vast number of diseases and disabilities, including Parkinson’s disease, diabetes and spinal cord injuries. One of the most exciting elements of reprogrammed cells is that the patients would be their own donors.

A new dilemma?

Statements like the one made by Rigali had Neaves wondering if pro-life activists fully understood the implications of Yamanaka’s and Thomson’s conclusions.

“The issue that has been overlooked is that when one directly reprograms an ordinary body cell … one has transformed that ordinary skin cell into the functional equivalent of a fertilized egg,” said Neaves, whose center was the prime target in a 2004 Catholic church-led attack on stem-cell research in Missouri. In 2006, Missouri voters narrowly approved an amendment to the state constitution that protects embryonic stem-cell research in the state.

Neaves pointed to the June 6 paper in the journal Nature by Rudolph Jaenisch, a professor of biology at Massachusetts Institute of Technology. In that paper, Jaenisch reports that he was able to verify Yamanaka’s earlier research, which reprogrammed mice skin cells into stem cells that were pluripotent, meaning they can form many different kinds of tissue, just like embryonic stem cells. It was how Jaenisch came to this conclusion, Neaves said, that should worry opponents to embryonic stem cell research.

The team Jaenisch supervised at the Whitehead Institute for Biomedical Research, in Cambridge, Mass., created a genetically abnormal mouse embryo that consisted of only placenta rather than the entire fetus. The reprogrammed stem cells, called induced pluripotent stems (iPS), were injected into the embryo and then placed into a uterus. The combination of the placenta and the stem cells resulted in a late-term mouse fetus.

“This is the most stringent criteria anyone can use to determine if a cell is pluripotent,” said Jaenisch in a paper released by the Whitehead Institute.

And also presents new ethical problems for hardliners who oppose embryonic stem-cell research, Neaves pointed out.

“This argument that [Neaves] is making is a flawed argument,” said Fr. Tadeusz Pacholczyk, neuroscientist and director of education for the National Catholic Bioethics Center. “If you’re talking about that process itself, then you are talking about an alternative technique for deriving embryonic-type stem cells without involving any embryos at all. At this point there is no question that you have not utilized any kind of embryo anywhere in the entire process.”

But Yamanaka himself shares some concerns about ethical slippery slopes, according to an interview he gave the British publication New Scientist Dec. 14.

“I can make eggs as well as sperm from my own male iPS cells,” Yamanaka said. “What if somebody took those sperm and eggs from a single person and fertilized them? The result would not be a clone because of the way cells divide during sexual reproduction … but it would be something very strange and dangerous.”

Pacholczyk said the newly discovered approach remains ethical, however, until human eggs and sperm are introduced into the equation.

“The derivation of the pluripotent stem cells from skin cells is ethical,” he said. “Subsequent uses may or may not be ethical, depending on what you are proposing.”

But this kind of microscopic hair-splitting has badly confused the debate, said Daniel C. Maguire, ethics professor at Marquette University.

“We’ve been held back by people who confer personal status upon microscopic accumulation of cells, which is a remarkable leap of faith,” Maguire said. “There never really was an ethical problem there; however, if [cell reprogramming] is going to achieve the same results with equal good, then fine. People won’t be putting up unnecessary roadblocks in the way of this important research.”

Practical problems

Beyond the pluripotency tests, scientists and ethicists on all sides agree that practical matters will keep the debate going for some time.

Most important, the induced pluripotent stem cells derived from Yamanaka’s and Thomson’s experiments are currently useless for human therapy, because they employ retroviruses, a kind of virus that would wreak havoc in the human body.

“Theoretically, scientists should now be able to make patient-specific iPS cells quite easily,” Yamanaka told the New Scientist. “But at the moment we have to use retroviruses to carry the foreign material into the cells, which could generate tumors. At this stage the iPS cells should be used only for testing out new drugs, until we find ways of making the changes without using a retrovirus.”

In the meantime, scientists can’t just throw away all of the other modes of experimentation, Neaves said, pointing to the variety of research in his own institute. Stowers supports three laboratories that currently research stem cells. Liheng Li researches human adult cells found in bone marrow. Ting Xie studies ovarian stem cells found in fruit flies. Olivier Pourquié has begun to employ embryonic stems cells in his research of the muscle and bone of the spine, since a Missouri constitutional referendum passed in November 2006 that expressly legalized such research. Stowers Institute played a key role in pushing the passage of that referendum.

Neaves said the ultimate goal is not to create therapies with somatic cell nuclear transfer, the practice of placing the nucleus of an ordinary body cell in the cytoplasm of an egg to create a stem cell. This method is sometimes called therapeutic cloning, especially by opponents of the practice.

“The ultimate goal of all lines of this research is to be able, eventually, to reprogram ordinary body cells so that they could be used for therapy to replace cells that have been destroyed by injury or disease,” Neaves said. “Learning how to reprogram them safely and more naturally is a very important goal. There is still a very large role to be played in research by somatic nuclear transfer toward that objective.”

Thomson expressed that very sentiment in a Dec. 3 editorial in The Washington Post, cowritten with the executive publisher of Science, Alan I. Leshner, who is also CEO of the American Association for the Advancement of Science.

“We simply cannot invest all our hopes in a single approach,” they wrote. “Federal funding is essential for both adult and embryonic stem-cell research, even as promising alternatives are beginning to emerge.”

Hope on the horizon

But Pacholczyk points out that Yamanaka is not oblivious to the moral implications of using embryos for research.

“When I saw the embryo,” Yamanaka told The New York Times about an early stem-cell research project, “I suddenly realized there was such a small difference between it and my daughters.”

It seems fairly certain that both Yamanaka and Thomson will be considered two of the giants of stem-cell research. Back in 1998, Thomson’s research group reported it had isolated stem-cell lines from human embryos, the first successful attempt. That, in effect, began the debate as it exists currently.

Yamanaka was the first to reprogram skin cells into stem cells in mice, which many saw even then as foreshadowing a possible ethical solution to the debate. That the two innovators announced the first human skin-cell reprogramming successes on the same day, said Pacholczyk, is a turning point.

“It’s something that people have hoped for, people have talked about an alternative,” Pacholczyk said. “And one of the key angles from those who favor the destruction of embryos is that this was the only way to do it. And that kind of claim can no longer reasonably be made.”

Neaves said he is also somewhat hopeful that this debate will be quelled someday, but not so much by what happens in the petri dish.

“When people are unequivocally cured of diseases as a result of research with human embryonic stem cells and somatic nuclear transfer, that will help immensely,” Neaves said.

Michael Humphrey is a Kansas City, Mo., freelance writer.

National Catholic Reporter, January 11, 2008

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