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October 26, 2005

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Palo Alto Online

Publication Date: Wednesday, October 26, 2005

The line between faith and science The line between faith and science (October 26, 2005)

Stanford professor hopes to further stem cell research without destroying human embryos

by Jocelyn Dong

Dr. William Hurlbut was trying to have a conversation . Navigating the Pittsburgh, Pa., airport last week with cell phone in hand, he talked while hurrying to the gate, winding his way through security, buying a snack, hopping an intra-airport shuttle, and boarding the plane.

He should be used to obstacle-filled discussions by now. The conversation he's tried to hold with the nation for more than a year has been much the same.

Then again, his topic -- human embryonic stem-cell research -- is a tough sell.

Like abortion, embryonic stem-cell research has stirred bitter controversy throughout the nation, as well as the world. Touching upon politics, science and morality, it has led to emotionally charged arguments laden with hyperbole and predictions that one day the country may see a patchwork of red-state and blue-state medicine.

The ethical hearts of both the abortion and stem-cell debates center on the definition of when life begins. Is a days-old embryo -- which gives rise to the stem cells -- something worth preserving and defending? Or is it merely a clump of cells that shouldn't be considered a human being?

Add to the issue the promise stem cells hold of possibly curing or at least treating dozens of diseases. Stem cells have the unusual ability to turn into any type of cell or tissue in the body -- blood, muscle, neurons and more.

It is in the midst of this complex and divisive national dispute that Hurlbut, 59, has landed.

The consulting bioethics professor at Stanford University and physician was named to the President's Council on Bioethics in 2001. Since then, he's been trying to find a way to bring about broad consensus within the nation. Instead, his ideas on how to create stem cells without involving embryos have sparked a controversy all their own.

That he considers himself an "apolitical" person only adds to the irony.

"Here I am in my small way opening up this project, and people all over the world are hearing about it," he said with a touch of incredulity.

In a polarized world, Hurlbut is a rare breed -- a Christian with pro-life concerns who is also pro-stem-cell research. That combination has left him to walk the delicate line between faith and science.

His specific goal is to figure out how to create stem cells that are as potent as ones derived from embryos, but which don't require an embryo's destruction.

His idea: a technique called "altered nuclear transfer," which involves an unfertilized egg and an adult cell. Scientists pluck out the nucleus of the adult cell and alter one or more of its genes. They then remove the egg's nucleus. The adult-cell nucleus is inserted into the egg, which then is electrically stimulated into growing.

After the egg begins to divide and develop, researchers extract the stem cells. Additional gene alteration returns the cells to normal functioning.

The key point, according to Hurlbut, is that the gene-altered egg is not an embryo and would never become a person because it doesn't have the necessary biological materials. Since it is not an embryo, it would not be "destroyed' when stem cells are taken out and thus would be morally acceptable, he said.

The creation is not as Frankenstein-like as it sounds; Hurlbut's entity has precedent in nature.

The teratoma is an ovarian tumor that is not considered human life -- yet can produce different biological matter, like hair and even teeth. However, its growth is disorganized and lacks the coordination among cells necessary to create an integrated human being.

Last week, the science journal "Nature" lent Hurlbut's idea credibility: An article noted that researchers at the Whitehead Institute for Biomedical Research in Massachusetts tested Hurlbut's altered-nuclear-transfer concept with mice and proved it could produce functional stem cells.

One would think all sides in the debate would welcome such an idea. Not necessarily. In fact, some have accused Hurlbut of merely adding fuel to the fire.

Perhaps it's not surprising, given the politically charged history of embryonic stem-cell research.

In 1995 and each year since, the U.S. Congress has approved and renewed the Dickey Amendment -- legislation that prohibits federal funding of research that involves the creation or destruction of human embryos for research purposes.

In 2001, President George W. Bush authorized federal funding for research using embryonic stem-cell lines that were already existing, while ordering federal monies not be given to research that created new embryo-derived lines.

Earlier this year, the U.S. House of Representatives passed a bill trying to reverse President Bush's decision by allowing donated embryos from in vitro fertilization clinics to qualify for federal funding. It has yet to be considered by the U.S. Senate.

Meanwhile, other legislation -- some supportive of adult stem-cell work (which does not involve embryos), one authorizing funding for all embryonic stem-cell research -- has also been thrown into the fray.

Hurlbut's harshest critics charge him with partisanship -- an accusation he flatly refutes. They say his proposal, far from trying to bring all sides together, is nothing more than a veiled attempt to end embryonic stem-cell research.

"I think this is a red herring," said David Magnus, director of the Stanford Center for Biomedical Ethics and an associate professor of pediatrics, medicine and philosophy. Alternate methods for deriving stem cells "are not really a compromise, they're a stopping action."

The real purpose of forwarding so-called "ethical alternatives" is to block legislation trying to loosen the current federal restrictions, he said.

Magnus holds no hope that people who oppose embryonic stem-cell research on moral grounds will ever be won over. Techniques like Hurlbut's may convince a few more people to support the research, but "not the bulk of them," Magnus said.

Even if a few were to be persuaded, he finds it "a bad principle" to try and get everyone to support a scientific method.

"Should science only be done if the country agrees with it?" he asked rhetorically.

Hurlbut disagreed, contending that social consensus is absolutely necessary.

"A purely political solution will leave our country bitterly divided, eroding the social support and sense of noble purpose that is essential for the public funding of biomedical science," he wrote in defense of the technique.

There's a long-term benefit in achieving a consensus, he said. This type of issue is not going to go away anytime soon.

"We're entering the age of developmental biology. The embryonic stem-cell conflict is just the beginning. It's the first symbolic argument between science and moral concerns (in a new era). We need to get this right," he said. "We need to go forward as a unified civilization."

Politics aside, Hurlbut also faces opposition from those who, ironically, claim a similar pro-life position. They assert Hurlbut hasn't solved the ethical problem.

David Schindler, academic dean of the John Paul II Institute for Studies on Marriage and Family at The Catholic University of America, wrote a response criticizing Hurlbut's proposal, in consultation with a group of seven other theologians and scientists. He contends there is no way to know that the entity created by altered nuclear transfer is not an embryo.

"We do not find their argument persuasive that their procedure certainly precludes that possibility that there would be an embryo. The fundamental question that we're not satisfied that they've answered is whether what is being produced is a radically defective embryo or not an embryo at all."

If it's an embryo, it would be considered life, and therefore worth defending, Schindler said.

Rather than continuing research with embryonic stem cells, scientists ought to work with adult cells only, Schindler said. "Adult stem-cell research seems to me is a much better way to go -- for ethical reasons."

He cited the treatments adult stem cells have produced for a range of diseases, adding that the younger field of embryonic stem-cell research is still waiting for results. (See sidebar.)

Hurlbut rejects Schindler's "disabled embryo" analysis. The determining factor in whether an entity deserves protection is if it has the potential to become a human, Hurlbut said.

"Potential is actual. There's a potency in a human being that is not to be found in something like a manufactured product. Living beings -- unlike manufactured products, which are not complete until they're fully assembled -- living beings assemble themselves. They do so because they're bearers of an active potential, not a theoretical potential," he said.

That may sound like an argument for Schindler's perspective, but Hurlbut explained further.

The altered nuclear transfer method engineers an egg-and-nucleus combination from the beginning that will not become a human embryo, he said. By turning off one of the nucleus' genes -- scientists are testing Cdx2, but Hurlbut says others may work as well or better -- the egg cannot "assemble itself" into an integrated, coherent being.

"The very definition of an embryo is that phase of human life which is unfolding along the trajectory of human development. If it does not carry in itself the capacity to do that, it's not a human embryo," Hurlbut said. "I wouldn't propose it if it were an embryo."

Hurlbut predicts the altered nuclear transfer method could produce a line of stem cells within a year or two, based on discussions he's had with researchers.

But as with all scientific work, new techniques face technological hurdles, and researchers routinely caution that an idea may not develop into a treatment for a variety of reasons.

One such person is David Greenwood, executive vice president of Geron in Menlo Park, a biopharmaceutical company that develops cell-based therapies derived from embryonic stem cells for chronic diseases.

Although academic scientists conduct research to answer basic biological questions, that doesn't mean treatments -- or as Greenwood calls them, "products" -- are right around the corner.

For one thing, the scale and costs to creating a therapy may be prohibitive.

"It's an economic-viability question. You've got to put costs to these processes," he said, adding that Geron has no stake in the success or failure of alternate methods of creating stem cells, since it already works with established stem-cell lines.

ot all scientists oppose methods like Hurlbut has proposed.

Dr. Evan Snyder, professor and director of the Stem Cells and Regeneration Program at the Burnham Institute, a life-sciences research organization in La Jolla, Calif., is open to a variety of concepts.

Snyder's been involved in the ongoing discussion over embryonic stem cells and took part in an ethics conference with Hurlbut in July 2004.

Asking conference attendees what it would take to change their opinion to the opposite side, they received three answers, one of which specified "new data."

"All of a sudden, we realized data, that's in the realm of science. Could science find something that could bring about consensus?" Snyder recalled.

One attendee, a Dominican priest and former molecular biologist, said human "personhood" began once there was an organism. That in turn, Snyder said, led to speculation over whether there was a way to prevent "organization" of an organism from happening, thus preventing human life.

"What if you block the gene... would this make somebody of that philosophy happy?" Snyder recalled the group asking, along the lines of Hurlbut's proposal.

Like the Stanford professor, Snyder believes seeking social consensus has worth.

"Some people say, 'Aren't you catering to a small minority? Isn't this a waste of time and resources?' In a pluralistic society, there's intrinsic value to ... trying to achieve consensus if you can do that," he said. "As long as you don't detract from or divert resources from pursuing the goal, it's good to try to make the most people feel comfortable."

And that just may be the direction the country is heading -- toward "both/and" rather than "either/or."

Even Dr. Irving Weissman, director of Stanford Institute for Stem Cell Biology and Regenerative Medicine, concurred from a scientific and medical standpoint that alternate methods are worth investigating. He wrote an accompanying article in last week's online edition of "Nature," in which he stated: "I believe all of these attempts to advance and translate medical science should be pursued in parallel."

So where does that leave Hurlbut? For one thing, continuing to fly around the country trying to get senators and others to listen. Although he said his role is to inform officials rather than persuade them to adopt any particular legislation, it's his hope that there could be a stand-alone bill that funds altered nuclear transfer.

To use one of his favorite catch phrases, "I'm hoping to provide one little island of unity in a sea of controversy," he said.

He demurred when asked if he views himself as a "crusader."

"I never thought of myself as a crusader. That sounds too glorious," he chuckled.

In fact, dealing with political agendas "has been hard for me personally," he said. "I'm trained as a doctor. I have a healing mentality."

People's reactions have been part of the difficulty.

A few days after being named to the President's Council on Bioethics, he walked through the Stanford campus. "About half the people who stopped me had some harsh words for President Bush, and often said things like, 'Well, I hope you'll put some stem cells in his head.' And I had just met with the man and ... I felt he was very earnest and was articulating reasonable concerns," Hurlbut said.

Although he's had good conversations on the topic with many colleagues, not all have taken kindly to his stance.

"Occasionally they disdained me because I took a cautious position and in a few cases were downright rude and angry," he said.

That tension was apparent when the Weekly requested access to Stanford's stem-cell institute to take photographs of laboratory research for this article. A Stanford spokesperson refused, saying the university staff didn't feel "comfortable" with the idea and indicating the university did not want people thinking Hurlbut's work had anything to do with the institute.

Conflict aside, Hurlbut has also received support for his ideas. Thirty-five ethicists, science professors and theologians from around the country co-signed a joint statement supporting altered nuclear transfer.

He also has received support from officials with the Catholic church, and readily shared a copy of a letter from the Most Rev. William J. Levada, former archbishop of San Francisco, to President Bush urging support for Hurlbut's concept.

Given his views on embryo-derived stem cells, one might label Hurlbut as anti-science or indifferent to the great potential stem cells have for improving people's lives. He is not.

He waxes enthusiastic about stem-cell research, agreeing that much might be gained through the work.

What he wants, however, is for society to put moral boundaries on the research, likening the limits to a fence built along a cliff. With the fence in place, people -- and, by analogy, scientific research -- can go up to the edge without falling off.

"A lot of good will come from this if we do it morally. But a lot of bad will come from it if we don't do it morally," he said.

He still holds out hope that others will see things the way he does -- if he can get them to let go of their agendas.

"I think when we sit down together collectively and stop fighting, stop playing politics, stop being disproportionate in our claims, and really genuinely listen to one another, we'll find out we're all bringing something important to the discussion," he said. "We can find an answer to this."

Senior Staff Writer Jocelyn Dong can be reached at [email protected]

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