Stem Cell Pioneers

Despite federal opposition to embryonic stem cell research, the promise of medical benefits, academic freedom and profits in California is luring scientists to the field

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Prop. 71, among other things, provides funds for a new state agency, the California Institute for Regenerative Medicine. Its governing board will award grants to scientists based on the quality of their research proposals, which will be evaluated by other scientists. In September, the institute, headquartered in San Francisco, announced that its first grants will train scientists and clinicians in stem cell biology and attendant ethical and legal issues. The institute plans to fund stem cell research that is done within the state's borders, "has the greatest potential for therapies and cures" and is "unlikely" to receive federal support. For now, however, lawsuits filed by opponents of Prop. 71 are holding up the distribution of money.

Klein, who heads a commission that oversees the new institute, says Prop. 71 will ultimately see up to a 236 percent return on its $3 billion investment. Klein gets his numbers from an analysis prepared by economic consultants during the campaign. The analysis predicts that new treatments will lead to healthcare savings, and that state coffers will enjoy revenues from taxes paid by biotech companies that flock to the field, as well as from a scheme that shares royalties if discoveries made with Prop. 71 funds come to market. This sunny forecast assumes that stem cell research will lead to medical advances for six diseases within 15 years—a promise that no one, of course, can make. Even the cheeriest prognosticators suggest it will take at least five years before any medicine based on human embryonic stem cell research proves to be safe and effective. And while $3 billion may seem like a huge budget, it has to last ten years and pay for both basic research and costly clinical trials.

Klein says California is putting its chips on "intellectual infrastructure," the equivalent of the bridges, harbors and roads that forward-thinking states built in the last century. "You're investing in knowledge that can have a 50 year or longer life of value," says Klein, who sounds like a politician on the stump but insists he has no ambition to run for public office.

Klein mixes the personal with the political. A U.S. Senate bill that repeatedly has died in committee and then resurfaced would make using cloning techniques on human cells—regardless of whether the goal is a baby or a line of stem cells for therapy—a crime punishable by up to ten years in prison. If the bill became law, says Klein, he could face a prison term and a $1 million fine for taking his diabetic son to another country for treatment with therapeutic cloning. "They're going to deny families access to this therapy outside this country," says Klein, sounding incredulous. He warns that despite the passage of Prop. 71, the proposed Senate bill to criminalize cloning, and other opposition, could undermine California's stem cell revolution. "Realize that we have won a major battle, but we have not won the war," he says. "Unless we stand up now, we will not have the opportunity to change the future of medicine."

As fervently as Klein believes that Prop. 71 is good for California, the bottom line for him does not involve the state budget. It's about what this legislation means to his son, who faces a daily struggle to maintain blood sugar levels as well as the disease's potential long-term complications. "One of the fundamental benefits to my son is hope," he says. "And that hope doesn't have to be that it will cure the disease. Its hope that he won't have blindness. Hope that he won't have kidney loss. It's a major hope that you don't lead your life with multiple amputations. That would be a huge blessing."

A short walk from Irv Weissman's spacious office and sprawling lab on the Stanford campusis the cramped workplace of one of his principal adversaries in the stem cell debates, William Hurlbut, 59, a physician. Hurlbut earned his undergraduate and medical degrees at Stanford and has known Weissman for 30 years. As a member of the President's Council on Bioethics, he has President Bush's ear. But many of his academic counterparts all but groan when he speaks: not only does Hurlbut mix religion and science, he proposes what they see as dubious scientific solutions to sidestep the ethical minefields. "I'm basically persona non grata, as you can imagine, with my colleagues," says Hurlbut.

Hurlbut also has a child whose condition helps shape his thinking. Three decades ago, a week after he graduated from medical school, Hurlbut's wife went into labor with a breech baby, which required an emergency Caesarean section. Just then, he says, another woman giving birth at the hospital had a sudden, life-threatening problem. "Everybody ran to take care of her and left my wife and baby unattended, and by the time they got back, there was no heartbeat," says Hurlbut. His baby daughter survived, but was severely brain damaged. "From that point, life became so difficult I simply couldn't return to clinical medicine," says Hurlbut, who went on to do postdoctoral studies in Christian theology and medical ethics. Today, he teaches biomedical ethics at Stanford University. His daughter Sarah is 30 and has serious cognitive and emotional disabilities, but Hurlbut says "by some good blessing she is much better off than anyone expected," and can walk and talk, remember things, and "see deeply into the hearts of others. . . . She's a perfectly worthy-to-be-alive human being," he says.

When Hurlbut joined the President's Council in 2002, he decided to rethink his beliefs, what he calls his "seamless garment of a pro-life perspective from conception to natural death." Ethicists and theologians had made many intriguing moral arguments he wanted to weigh, such as the possibility that life begins at 14 days, the point that defines individuality because the embryo no longer can split into identical twins. "I both support and am excited by the speculative but interesting possibilities of embryonic stem cell research," says Hurlbut. "I just don't support getting the embryonic stem cells from the disaggregation of living human embryos. I feel worse about it when they are intentionally created, but I also have concerns about the use of IVF spares." And he opposes the prospect of creating embryos to serve, in his words, as body shops to "harvest parts."

Hurlbut ended up rejecting the 14-day argument, but he arrived at what he considers an ethically acceptable way forward. He advocates what he calls "altered nuclear transfer." Nuclear transfer is the procedure that created Dolly, by merging a body cell with an emptied egg. Hurlbut proposed that researchers alter genes during the nuclear transfer process so that the cells would not turn into a functional embryo but could still yield embryonic stem cells. In October, researchers from the Massachusetts Institute of Technology showed that they could do this in mouse embryos. Hurlbut praised the work as a big step forward.

Although the mouse study shows that Hurlbut's proposal is feasible, some of the field's foremost researchers say he downplays the technical hurdles of adapting the approach to human embryos. And, they say, there's nothing morally wrong with research that uses normal early embryos. Weissman has a slightly more charitable reaction. "When Bill Hurlbut says do that, I say, Go to it," Weissman shrugs. "Don't talk about it. Do it."


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