The Hard Cell

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Work on the heart is furthest along because it is a comparatively simple organ and easy to access with a catheter. Initial studies use adult stem cells from the patient's bone marrow, which lack potential to become other cell types but don't carry the political and ethical baggage of embryonic stem cells. And much is already known about them — bone marrow transplants have been routine treatment for leukemia since the 1970s.

Interest in using adult stem cells to repair the heart took off in 2001, after U.S. researchers reported that mice in which they had induced heart attacks recovered up to 37% of their lost heart function within seven to 11 days of having the cells directly injected into their hearts. In 2001, researchers at the Hospital of the Johann Wolfgang Goethe-University in Frankfurt tried the technique on 20 people, who recovered an average of 7% of left ventricular ejection fraction, a measure of the heart's ability to empty itself. Though it sounds marginal, a 7% improvement may give some patients sufficient heart function. "The challenge of science is to improve on those numbers," says Mathur.

Still, skeptics question whether trials like his are premature while stem cells' mechanisms remain poorly understood. Some scientists theorize that either the cells or growth factors added to them enable new vessels to form in the heart, but no one is sure. "There is something to it, but you need much more bench work," says Michael Marber, a professor at King's College London who is skeptical of the trials. "What we need at the moment is to understand more of the basic biology." The trials' sponsors argue that such additional research could take years and delay new treatments. "Our understanding of many therapeutic interventions in the heart is provisional," says John Martin, a professor at University College London, who is collaborating with Mathur in a related trial on patients immediately after heart attacks. "We still don't understand how aspirin or beta-blockers work."

So far at least, no harm has come to Mathur's first 40 patients as a result of the procedure. Stem cells from a patient's own bone marrow are unlikely to be rejected by their immune systems. But other studies suggest proceeding cautiously. Patients in France and Holland who had skeletal muscle tissue transplanted from their limbs to their hearts developed irregular heartbeats that required electric shocks to restore the rhythm to normal. At least two cases ended in death. Mice treated with stem cells have developed tumors, suggesting renegade cells can grow uncontrollably.

Experimental science usually proceeds by trial and error, and patients like Johnson accept its risks because their conditions carry a poor prognosis. "I have nothing to lose and I might benefit from it," he says. After Mathur's trial was launched, his hospital's switchboard was inundated by 1,000 calls from would-be participants around the world. All the attention creates high expectations which, if unmet, can lead to disappointment. And there are obvious limits: patients with spinal cord damage who expect stem cells to enable them to walk someday, says Martin, are probably being unrealistic.

Progress toward stem-cell therapies is more likely to be incremental and selective. Look at Johnson: three months after his treatment, he says he feels about the same as he did before it, though it's probably too early to know if the treatment has helped him. He has a check-up with Mathur at year end and will be monitored until 2010. By that time, it might be clear whether stem-cell research is a leap forward or a blind alley.