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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Other alternative strategies for harnessing the potential of stem cells exist, the most widely discussed of which involves adult stem cells, Weissman's area of expertise. Scientists have discovered human adult stem cells in the blood and in several organs including the heart and brain. Some research has suggested that adult stem cells may perform as nimbly as embryonic stem cells, able to turn into almost any type of cell in the body if manipulated correctly. Few assertions rile Weissman more, and he has spent countless hours debunking those studies. "I'd have been delighted if blood-forming stem cells or brain-forming stem cells could make or repair any other tissue, and so would the companies I helped found," says Weissman. "We tested the claims rigorously,"he says, "and they failed."

Scientists recently promoted another way to dodge ethical questions about embryonic stem cells. IVF clinics routinely remove one cell from an embryo implantation to test it for genetic abnormalities. Babies born from embryos so modified do not appear to suffer any harm. In October, researchers working with mice reported that they could make an embryonic cell line from such a removed, single cell. Weissman cautioned, however, that it was "highly speculative" whether the same procedure would work in humans.

And Weissman, like many of his colleagues, sees an ethical dilemma created by the notion that today's research should stop, as many opponents of embryonic stem cell research demand, until scientists discover less contentious methods. "If we delay, and in that delay, for no good reason as far as I could see, people are dying who had a chance to live, that's morally unacceptable to me," he says.

Weissman points out that most people who object to destroying human embryos for research don't protest IVF itself, which routinely produces embryos that end up being destroyed. Hurlbut, for his part, calls this seeming contradiction "the single hardest question," but says the issue is ethically different because IVF clinics aim to create life.

Hurlbut urges stem cell researchers to more aggressively explore strategies that do not destroy viable embryos. "We've just put our feet onto Plymouth Rock," he says. "We have a whole continent to explore. It's too early to say which one of these approaches will lead to the most fruitful science and clinical applications."

One of the most puzzling phenomena in all of biology today is that an egg can turn an adult cell into an embryonic one, that is, the cloning phenomenon. "We have to learn how the egg does it," Rudolf Jaenisch tells Goldstein, Weissman and a few hundred other colleagues gathered to hear his keynote lecture at the Stem Cell Biology and Human Disease conference at the Salk Institute in March. "It's not a miracle. It's a biochemical reaction."

Jaenisch is the prominent Massachusetts human embryonic stem cell researcher whom Weissman hopes to recruit to Stanford. Jaenisch and his colleagues at the Whitehead Institute for Biomedical Research in Cambridge are investigating the mechanisms by which an egg that has had its own genetic material removed, when fused with a body cell, instructs that cell to revert to an embryonic one—the process behind Dolly the sheep and made-to-order embryonic stem cell lines. If researchers can solve this mystery, they will vastly simplify their work. The current method for cloning depends on eggs that women donate—a medical procedure that involves injecting fertility drugs into donors and having follicles removed from their ovaries, which carries some risk and is, at the very least, uncomfortable. If scientists could somehow reprogram adult cells to turn into embryonic stem cells on their own, ethical debates might dissolve. Scientists no longer would need to create or destroy embryos to harvest embryonic stem cells.

The Salk Institute gathering attracted a who's who of stem cell researchers from around the globe, who together, have made progress using the cells to cure diabetes, Parkinson's, immune deficiencies, heart disease and brain injuries—in mice. When it comes to human disease, no group has moved further than the one led by another speaker at the meeting, South Korea's Woo Suk Hwang, whose team created, in 2004, the first human embryonic stem cell lines using cloning techniques. (It was also Hwang and his colleagues who cloned the first dog, an Afghan hound named Snuppy, reported this past August.) His lab has now made embryonic cell lines from people who have spinal cord injury or immune disorders, a first step toward using personalized cultured cells to study these afflictions.

Scientific meetings function something like county fairs, except instead of trotting out prize Holsteins or giant tomatoes, participants show off their latest data and ideas. Most of the advances are incremental and would have little meaning to people who don't wear white lab coats. But many of the ideas, which rely more on imagination than evidence, are dazzling. One researcher talks about her dream of engineering the scaffolding of a liver with synthetic material, and then implanting liver stem cells onto it to make a functioning organ. Several scientists discuss the possibility that cancer is caused by haywire stem cells. Others wonder whether chemicals secreted by stem cells, rather than the cells themselves, might have healing powers.

A Harvard University researcher opens his talk by thanking Weissman and Goldstein for their work on Prop. 71."You guys have done a tremendous amount for the field and our nation," he says.


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